YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA MCI (P) 030/07/2024 SINGAPORE NOVEMBER 2024

Highlights from EADV & HFSA 2024

Drugs vs

surgery for weight loss:

options

The better

of 2

CONTENTS

MIMS DOCTOR - YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA

NOVEMBER ISSUE

Managing Editor

Elvira Manzano

Contributing Editors

Stephen Padilla, Jairia dela Cruz,

Elaine Soliven, Audrey Abella,

Christina Lau, Natalia Reoutova,

Kanas Chan, Mike Ng

Senior Designer

Fei Ching Chan

Production & Advertising Coordinator

Raymond Choo

Circulation Executive

Christine Chok

Finance Associate Director

Chee Kean Tan

CEO

Masaki Takahata

Published by

MIMS Pte Ltd

438B Alexandra Road,

Alexandra Technopark

#06-11 Singapore 119968

Tel: (65) 6290 7400

Fax: (65) 6290 7401

Email: enquiry@mimsdoctor.com

Advertising Enquiries:

China

Yang Xuan

Tel: (8621) 6157 3888

Email: enquiry.cn@mims.com

Hong Kong SAR

Rio Lee, Serena Cheung, Nicky Yip,

Joanne Cheung, Francis Cheng

Tel: (852) 2559 5888

Email: enquiry.hk@mims.com

Indonesia

Ruth Theresia

Tel: (62 21) 729 2662

Email: enquiry.id@mims.com

AUSTRALIA ? CHINA ? HONG KONG SAR

INDIA ? INDONESIA ? MALAYSIA ? MYANMAR

NEW ZEALAND ? PHILIPPINES ? VIETNAM

SINGAPORE ? SOUTH KOREA ? THAILAND

1

DOCTOR | NOVEMBER ISSUE

4

7

8

9

10

12

13

14

15

16

17

18

19

20

Cover Story

Drugs vs surgery for weight loss: The better of 2 options

COVID-19 Extra

Long-term benefi ts of molnupiravir modest at best for COVID-19

Large UK study underpins role of COVID-19 vax in mental illness

COVID-19 vaccine acceptance low among mothers

Autism risk in children not heightened by COVID-19 exposure

Conference Coverage

European Academy of Dermatology and Venereology (EADV)

Congress 2024, September 25-28

Phototherapy for psoriasis at home as good as in the offi ce

TYK2 inhibitor looks good for lichen planopilaris

Upadacitinib superior to dupilumab in patients with moderate-to-severe AD

Long-term secukinumab works for kids with chronic plaque psoriasis

Real-world study supports tralokinumab for diffi cult-to-treat AD

Patients with scalp psoriasis experience fi rst-hand improvements in itch,

fl aking, pain from deucravacitinib

Psoriasis patients with overweight, obesity may need higher vunakizumab doses

DISCREET highlights apremilast potential for genital psoriasis

Remibrutinib off ers rapid, sustained symptom relief in patients with CSU

7 14

India

Joe Thomas

Tel: (9180) 2349 4644

Email: enquiry.in@mims.com

Malaysia

Rachel Liew, Vicky Dharma, Xavier Wee,

Rathika Nagarajan, Nurshamin Mashkon

Tel: (603) 7623 8000

Email: enquiry.my@mims.com

Philippines

Mary Ann Achacoso-Luz,

Marilen Cabanban, Wilma Calderon,

Gracia Cruz, Mae dela Cruz,

Noriel Escueta, Marvin Osea,

Teresa Rabago, Jay-R Rivera,

Richard Rivera, Martin Tan,

Rowena Velasquez

Tel: (632) 8657 1767

Email: enquiry.ph@mims.com

Singapore

Jasmine Tan, Janice Tan,

Jackson Tu, Anuar Ibrahim,

Kelly Ko, Stephanie Lee

Tel: (65) 6290 7462

Email: enquiry.sg@mims.com

Thailand

Lup Yee Yau

Tel: (66) 2114 3655

Email: enquiry.th@mims.com

Vietnam

Nguyen Thi Lan Huong,

Nguyen Thi My Dung

Tel: (848) 3829 7923

Email: enquiry.vn@mims.com

To subscribe:

subscribe.sg@mimsdoctor.com

To contact the editor:

editor.sg@mimsdoctor.com

To submit an article:

contribute.sg@mimsdoctor.com

438B Alexandra Road,

Alexandra Technopark

#06-11 Singapore 119968

HOW TO CONTACT US

CONTENTS

MIMS DOCTOR - YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA

NOVEMBER ISSUE

2

DOCTOR | NOVEMBER ISSUE

Ebdarokimab works well for plaque psoriasis

Post hoc analysis bolsters trifarotene role in acne scar management

As-needed ruxolitinib in children with AD: Disease control stable

through 52 weeks

Hidradenitis suppurativa patients get durable benefi t with bimekizumab

Topical delgocitinib holds the lead over oral systemic Tx in head-to-head hand

eczema trial

Risankizumab eases symptoms in nonpustular palmoplantar psoriasis

Data support abrocitinib use beyond 2 years in adolescents with AD

Conference Coverage

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024,

September 27-30

Cardiac biomarker profi le in ATTR-CM looks good with vutrisiran

Evidence supports semaglutide for obesity-related HFpEF

Novel HU6 reduces weight without muscle loss in patients

with obesity-related HFpEF

Mavacamten improves cardiac biomarkers in patients with HFpEF

Mitral TEER clips hold benefi ts at 1 year in patients with atrial SMR

Are SGLT2 inhibitors cardioprotective for wild-type ATTR-CM patients?

Acoramidis boosts clinical outcomes in ATTR-CM

Thumbs up for HeartMate 3 in cohorts with high perioperative risk

Afi camten improves clinical outcomes in obstructive HCM

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

39

2

MIMS Doctor is published 12 times a year

by MIMS Pte Ltd. MIMS Doctor is on controlled circulation publication to medical

practitioners in Asia. It is also available on

subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail);

back issues at US$5 per copy. Editorial

matter published herein has been prepared

by professional editorial staff . Views expressed are not necessarily those of MIMS

Pte Ltd. Although great eff ort has been

made in compiling and checking the information given in this publication to ensure

that it is accurate, the authors, the publisher and their servants or agents shall not

be responsible or in any way liable for the

continued currency of the information or

for any errors, omissions or inaccuracies in

this publication whether arising from negligence or otherwise howsoever, or for any

consequences arising therefrom. The publisher bears no responsibility or liability for

patent ownership or patent legality of any

medical product mentioned or featured, nor

is it responsible for verifying the ownership

or originality of the product which, therein infringes upon the intellectual property

rights or other rights of any third party. The

inclusion or exclusion of any product does

not mean that the publisher advocates or

rejects its use either generally or in any

particular fi eld or fi elds. The information

contained within should not be relied upon

solely for fi nal treatment decisions.

? 2024 MIMS Pte Ltd. All rights reserved.

No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted,

in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the

copyright owner. Permission to reprint must

be obtained from the publisher. Advertisements and advertorials are subject to editorial acceptance and have no infl uence on

editorial content or presentation. MIMS Pte

Ltd does not guarantee, directly or indirectly, the quality or effi cacy of any product or

service described in the advertisements or

other material which is commercial in nature.

Philippine edition: Entered as second-class

mail at the Makati Central Post Offi ce under

Permit No. PS-326-01 NCR, dated 9 Feb

2001. Printed by KHL Printing Co Pte Ltd,

57 Loyang Drive, Singapore 508968

MCI (P) 030/07/2024

ISSN 2410-7808

CONTENTS

MIMS DOCTOR - YOUR MOST TRUSTED SOURCE OF HEALTHCARE INFORMATION IN ASIA

3

DOCTOR | NOVEMBER ISSUE

NOVEMBER ISSUE

37

39

41

42

43

44

45

46

47

49

Pharmacists in Focus

Beyond medication dispensing: The expanding role of pharmacists in healthcare

Focus on Antimicrobial Resistance

Over 39M people could die from superbugs by 2050

Newsbites

Extreme rainfall puts people’s lives at risk

In utero exposure to fl u spells increased risk of childhood seizures

Happiness key to a healthy heart

Research Review

Curcuma supplements benefi cial for AMD?

Hearing loss a red fl ag for PD

Clinical Insights

DEVICE

What educational topics on smartphone apps matter to RMD patients

Handheld skin analysis device delivers reliable skin age, health readings

Calendar

Humour

29

4

DOCTOR | NOVEMBER ISSUE

COVER STORY

ELVIRA MANZANO

I

n a fi rst-of-a-kind meta-analysis comparing the effi cacy and safety of diff erent treatment options for obesity, weight

loss surgery using the Roux-en-Y gastric

bypass (RYGB) yields optimal weight loss

than other surgical procedures or weight

loss medications.

“As for tirzepatide, this long-acting

dual GIP and GLP-1* receptor agonist

performed just as well, with favourable

safety profi le,” reported principal investigator Dr Jena Velji-Ibrahim from Prisma

Health–Upstate/University of South Carolina School of Medicine in Greenville,

South Carolina, US at the recent American College of Gastroenterology (ACG)

2024 Annual Scientifi c Meeting.

“There was no signifi cant diff erence

in total body weight loss percentage between tirzepatide and one-anastomosis

gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she added.

All 11 interventions studied produced

weight loss eff ects, and side-eff ect profi les were largely favourable, particularly

for endoscopic interventions.

Surgery vs medication

Velji-Ibrahim and colleagues conducted a literature search to identify randomized controlled trials (RCTs) comparing

the effi cacy of US FDA-approved bariatric surgeries, bariatric endoscopies, and

medications in adults with a

BMI of 25–45 kg/m2

, with or

without type 2 diabetes.

[ACG 2024, abstract 46]

“Tirzepatide

performed just as

well, with favourable

safety profi le”

After that, a network meta-analysis

was performed to assess the impact of

the various interventions on the percentage of total weight loss and side-eff ect

profi les. P-scores were calculated to rank

the treatments and identify the preferred

interventions. The therapy lasted for 52

weeks.

Overall, 34 RCTs with 15,660 patients

were included in the analysis. The RCTs

analysed weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and

medications (four studies).

The bariatric surgeries included

RYGB, laparoscopic sleeve gastrectomy, OAGB, and laparoscopic adjustable

gastric banding. Bariatric endoscopies

included endoscopic sleeve gastroplasty, transpyloric shuttle, and intragastric

balloon. As for weight loss medications,

tirzepatide, semaglutide, and liraglutide

were included.

Battle of weight loss

interventions

“When comparing bariatric surgery

with bariatric endoscopy, endoscopic

sleeve gastroplasty and transpyloric

shuttle provided a minimally invasive alternative, with good weight

loss outcomes and fewer adverse

events,” said Velji-Ibrahim.

She noted that current studies comparing

weight loss interventions

have been limited by relatively

small sample sizes, observational designs, and conflicting

outcomes. Velji-Ibrahim said the meta-analysis was borne out of this need.

Treatment of choice

“Although all interventions were associated with reductions in the percentage

of total weight loss compared with placebo, RYGB led to the greatest reductions

(19.29 percent) in weight and was ranked

the most preferred treatment (97 percent

probability),” she reported.

RYGB was followed by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg.

Tirzepatide 15 mg provided a slightly

lower total weight loss percentage (15.18

percent) with a favourable safety profi le. There was no signifi cant diff erence

in total weight loss percentage between

tirzepatide 15 mg and OAGB (mean difference, 2.97 percent) or laparoscopic

sleeve gastrectomy (mean diff erence,

0.43 percent).

Additionally, no signifi cant diff erence

was found in total weight loss percentage

between semaglutide 2.4 mg compared

with endoscopic sleeve gastroplasty and

transpyloric shuttle.

Endoscopic sleeve, transpyloric shuttle, and intragastric balloon all resulted in

weight loss of >5 percent.

“Compared with bariatric surgery,

endoscopic interventions had a better side-eff ect profi le, with no increased

odds of mortality and intensive care requirements,” Velji-Ibrahim pointed out.

“As for medications, the most common side eff ects were gastrointestinal

in nature, which included nausea, vomiting, diarrhoea, and constipation,” she

added.

Combination modalities

Session co-moderator Dr Shivangi

Kothari from the University of Rochester

DOCTOR |

the effi cacy of US FDA-approved bariatric surgeries, bariatric endoscopies, and

medications in adults with a

BMI of 25–45 kg/m2

, with or

without type 2 diabetes.

[ACG 2024, abstract 46]

“When comparing bariatric surgery

with bariatric endoscopy, endoscopic

sleeve gastroplasty and transpyloric

shuttle provided a minimally invasive alternative, with good weight

loss outcomes and fewer adverse

events,” said Velji-Ibrahim.

rent studies comparing

weight loss interventions

have been limited by relatively

small sample sizes, observational designs, and conflicting

5

DOCTOR | NOVEMBER ISSUE

COVER STORY

Drugs vs

surgery for weight loss:

options

The better

of 2

COVER STORY

Medical Center in Rochester, New York,

US, however, said the future of obesity

management is not just about weight loss

percentage, “rather, it will be about how

well weight loss is sustained post-intervention.”

“The future will be about moving away

from comparing one modality or intervention to another. Instead, we should be

looking at combination therapies in future

trials, which could be the best intervention for patients with obesity,” she emphasized.

Endoscopic bariatric surgery

+ GLP-1 RA

Kothari’s aspirations were not that

far off . A separate systematic review,

also presented at ACG 2024, analysed

the combination of endoscopic bariatric

intervention (endoscopic sleeve gastroplasty or intragastric balloon) plus a GLP1 RA vs endoscopic bariatric therapy

alone in patients with obesity.

Three retrospective studies involving

266 patients, 143 of whom underwent

endoscopic bariatric treatment alone,

were analysed. They were compared

with 123 patients treated with bariatric

surgery and a GLP-1 RA, specifi cally liraglutide. [ACG 2024, abstract

P3159]

The outcome of interest

was the standardized mean

diff erence (SMD) of the

mean absolute body weight loss

during follow-up.

“Both pharmacologic and surgical

treatments are eff ective options for obesity,” said another study author Dr Nihal Ijaz

Khan from AdventHealth Medical Group,

AdventHealth, Orlando, Florida, US. “Our

analysis shows the superior absolute

weight loss achieved by patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment compared with

endoscopic bariatric treatment alone.”

The SMD in body weight loss between

endoscopic bariatric treatment + GLP-1

RA and endoscopic bariatric treatment

alone was 0.61 (95 percent confi dence

6

DOCTOR | NOVEMBER ISSUE

“We should be looking at

combination therapies in

future trials, which could

be the best intervention

for patients with obesity”

“Our analysis shows the superior absolute

weight loss achieved by patients receiving

GLP-1 RAs in combination with endoscopic

bariatric treatment compared with

endoscopic bariatric treatment alone”

- Dr Nihal ljaz Khan

interval [CI], 0.35-0.86; p<0.01; I2 of 91

percent) at follow-up.

“Further studies are warranted to

evaluate the safety and adverse events

comparing these two treatment modalities,” said Khan. “These could also uncover the diff erences between comparing

the two endoscopic options to various

GLP-1 RAs,” he concluded.

*GIP and GLP-1: glucose-dependent insulinotropic

polypeptide and glucagon-like peptide-1

7

DOCTOR | NOVEMBER ISSUE

JAIRIA DELA CRUZ

The antiviral molnupiravir confers

continued but modest benefi ts

in reducing COVID-19–related

symptoms up to 6 months after the

index infection in a vaccinated population, according to a secondary analysis

of the PANORAMIC trial.

Long-term follow-up data from

23,008 participants (89.2 percent of the

trial population, mean age 57.2 years,

58.4 percent female, 94.7 percent

White, 99.1 percent had received at least

one vaccine dose) showed that “cough,

shortness of breath, fatigue, muscle

aches, and being generally unwell were

less prevalent in the molnupiravir plus

usual care group at 3 and 6 months,”

the investigators reported.

Relative to those who had received

usual care alone, fewer participants who

had undergone a 5-day course of molnupiravir in addition to usual care reported experiencing any symptoms that were

rated as severe (3 months: 16.9 percent

vs 18.3 percent, number needed to treat

[NNT]=62.5; 6 months: 16.5 percent vs

18.3 percent, NNT=52.6) or any persistent symptoms (3 months: 8.9 percent

vs 11 percent, NNT=47.6; 6 months: 8.5

percent vs 11.0 percent, NNT=40). [Lancet Infect Dis 2024;doi:10.1016/S1473-

3099(24)00431-6]

Participant rating of wellness was

higher in the molnupiravir plus usual care

Long-term benefi ts

of molnupiravir modest

at best for COVID-19

group than in the usual care alone group,

with an adjusted mean diff erence of 0.15

at 3 months and 0.12 at 6 months. The

same was true for health-related quality of life, with an adjusted mean diff erence in the EQ-5D-5L score of 1.08 at 3

months and 1.09 at 6 months.

Additionally, participants in the molnupiravir plus usual care group were

less likely to use any healthcare or social service at 3 months (14.1 percent

vs 15.5 percent; NNT=71.4) and at 6

months (8.9 percent vs 9.2 percent;

NNT=200), as well as to have taken

time off work or study at 3 months (17.9

percent vs 22.4 percent; NNT=18.9)

and at 6 months (4.4 percent vs 5.4

percent; NNT=90.9).

Very few participants were hospitalized due to COVID-19 during the

long-term follow-up, with no signifi -

cant between-group diff erence in either

COVID-19-related or all-cause hospitalizations at 3 and 6 months.

“Participant rating of wellness, any

symptom rated moderately bad or

worse, any persistent symptom, and

health or social care use, and time off

work were all statistically superior in the

molnupiravir plus usual care group at 3

COVID-19 EXTRA

“A large number of

patients would need

to be treated with

molnupiravir to see one

additional benefi cial

outcome compared

with usual care”

and 6 months but with small absolute

eff ects,” the investigators said.

“This study was a secondary longterm analysis, and although we did not

correct for multiplicity, the number of

statistically superior outcomes make

chance a very unlikely explanation of the

results,” they continued, noting however

that small absolute diff erences that are

statistically signifi cant may not necessarily be clinically meaningful.

In a news release, lead investigator

Dr Victoria Harris from the Nuffi eld Department of Primary Care Health Sciences in Oxford, UK, pointed to the fact that

the NNTs were high. This means that “a

large number of patients would need to

be treated with molnupiravir to see one

additional benefi cial outcome compared

with usual care.”

“For instance, only one person would

have less severe symptoms from a total

of 53 people who took molnupiravir, and

only one person would have used fewer

national health services from a total of

71 people who took molnupiravir. Given

the small additional number of participants who benefi ted from taking molnupiravir, compared with those who did

not take the drug, long-term health benefi ts will need to be weighed up against

costs and any unwanted eff ects,” Harris

stated.

In the UK, molnupiravir costs about

GBP 500 per course. As such, providing all COVID-19 patients with the drug

would have substantial fi nancial implications for the NHS. Harris and colleagues

believe that their data could help relevant stakeholders make decisions about

the long-term treatment of COVID-19.

DOCTOR | NOVEMBER ISSUE

COVID-19 EXTRA

Large UK study underpins

role of COVID-19 vax

in mental illness

AUDREY ABELLA

I

n a cohort study of over 18 million

individuals with up to 2 years of follow-up, the incidences of most mental

illnesses were markedly elevated following COVID-19 diagnosis compared with

before or without COVID-19, particularly among the unvaccinated and before

COVID-19 vaccines became available.

The study was conducted in three cohorts: one before vaccine availability, followed during the wild-type/Alpha variant

eras (January 2020 through June 2021),

and two during the Delta variant era (June

through December 2021). [JAMA Psychiatry 2024;doi:10.1001/jamapsychiatry.2024.2339]

The pre-vaccine availability cohort

included 18,648,606 individuals (median age 49 years, 50.2 percent women),

the vaccinated cohort had 14,035,286

participants (median age 53 years, 52.1

percent women), while the unvaccinated group included 3,242,215 individuals

(median age 35 years, 57.9 percent men).

The incidences of COVID-19 infection in

the respective cohorts were 1,012,335,

866,469, and 149,745.

Depression was the most common

mental illness, with 1,329,270, 352,944,

and 57,810 diagnoses in the pre-vaccine

availability, vaccinated, and unvaccinated

cohorts, respectively. The corresponding diagnoses of serious mental illness

in these cohorts were 397,368, 88,500,

and 18,726.

In each cohort, day 0 saw tremendously high incidences of all outcomes.

During the rest of week 1 through week

4 after COVID-19, the rates of most outcomes were higher than before

or without COVID-19.

During weeks 1–4 after

COVID-19, the adjusted hazard

ratios (HRs) for depression and

serious mental illness among

the vaccinated cohorts were

1.16 and 0.91, respectively.

The corresponding adjusted HRs were higher in the unvaccinated

(1.79 and 1.45) and pre-vaccine availability cohorts (1.93 and 1.49).

“[The] attenuation of adverse eff ects

of COVID-19 on mental illnesses in the

vaccinated may be explained by reduced

disease severity due to vaccination,”

the researchers explained. “Potential

mechanisms include reduced systemic

infl ammation and psychological benefi ts

of vaccination, such as reduced concern

about COVID-19 and increased social

engagement.”

On the other hand, the higher incidence of mental illnesses in the pre-vaccine availability cohort may refl ect the

greater uncertainty and public concerns

around COVID-19 outcomes and the effi cacy of treatment during the start of the

pandemic, they added.

Vaccination remains crucial

The eff ects of vaccination in preventing and reducing the severity of COVID-19

are well established, but data on its eff ects

on other adverse COVID-19 outcomes,

including mental illnesses, are lacking.

[Infect Drug Resist 2021;14:3459-3476;

BMJ 2022;377:e069317]

“[Our study shows that] the incidence

of mental illnesses was elevated for up to

a year following severe COVID-19 in unvaccinated people. These fi ndings suggest that vaccination may mitigate the

adverse eff ects of COVID-19 on mental

health,” the researchers said.

Of note, the likelihood of having

mental illnesses recorded may be higher

among individuals with COVID-19, particularly those who have been hospitalized,

given their greater contact with health

services. This may not be the case for

unvaccinated individuals, who may have

had fewer health service visits and testing

for COVID-19 infection, hence the potential for underestimated eff ects.

Nonetheless, the fi ndings underline

the importance of COVID-19 vaccination in the general population, specifi cally

among those with mental illnesses who

may be at higher risks of adverse outcomes following COVID-19 infections.

[Br J Gen Pract 2021;72:e51-e62; World

Psychiatry 2022;21:153-154; Mol Psychiatry 2022;27:1248-1255]

“Our fi ndings highlight the wider public health benefi ts of vaccination. Prior

mental illness may infl uence vaccine uptake, highlighting the importance of actively encouraging vaccination of people

with mental health diffi culties,” they said.

8

DOCTOR | NOVEMBER ISSUE

COVID-19 EXTRA

STEPHEN PADILLA

Pregnant and lactating women in

Singapore generally have low acceptance of the COVID-19 vaccine

due to safety concerns, reports a recent

study.

“Factors aff ecting low vaccine acceptability among both pregnant and lactating women included a low perceived

infection risk and concerns of unknown

safety for the mother and child,” the researchers said. “Addressing safety concerns and infection risk may help improve

COVID-19 vaccine acceptance among

pregnant and lactating women in Singapore.”

This anonymous, online survey on the

perception of the COVID-19 vaccine and

its acceptance by pregnant and lactating

women at a tertiary maternal and child

hospital in Singapore was performed

from 1 March 2021 to 31 May 2021. The

research team collected data on participant demographics and knowledge.

They then evaluated these factors for association with vaccine acceptance.

Overall, 201 pregnant and 207 lactating women responded to the survey. Vaccine acceptance rates were 30.3 percent

in pregnant women and 16.9 percent

COVID-19 vaccine acceptance

low among mothers

in lactating mothers. [Singapore Med J

2024;65:494-501]

For pregnant women who expressed

uncertainty or were unwilling to receive

the vaccine, their primary concern was

safety of the vaccine during pregnancy

(92.9 percent). For lactating mothers,

they cited the potential long-term negative eff ects of vaccination on the breastfeeding child (75.6 percent).

The following factors showed a positive association with vaccine acceptance:

lower monthly household income or education level, appropriate knowledge regarding vaccine mechanism, and higher

perceived maternal risk of COVID-19.

Notably, most pregnant (70 percent)

and lactating women (83.7 percent) were

willing to be vaccinated only when they

were provided with more safety data

during pregnancy and breastfeeding.

Safety concern

Many studies found safety concerns

of mothers about child health or their own

as the main reason for the low vaccine

acceptance. [Am J Obstet Gynecol MFM

2021;3:100403; Int J Environ Res Public Health 2021;18:3367; MMWR Morb

Mortal Wkly Rep 2021;70:895-899; Int J

Gynecol Obstet 2021;154:291-296; Am

J Obstet Gynecol MFM 2021;3:100399]

“Similarly, the lack of safety data for

the COVID-19 vaccine was a signifi cant

factor aff ecting vaccine acceptability in

our population,” the researchers said.

“Pregnant women were concerned

about general safety of the vaccine during

pregnancy, while lactating mothers were

concerned about the possible long-term

side eff ects that the vaccine could have

on their child,” they added.

The fi nding on safety concerns of the

participants were not surprising, given that

both pregnant and lactating women were

not included in the initial mRNA-based vaccine trials, resulting in limited available data

on safety and effi cacy in this population.

However, observational data from

other countries have demonstrated the

safety of mRNA-based vaccines in pregnant and lactating women without any

noticeable short- or medium-term adverse eff ect to the foetus or child. [Obstet

Gynecol 2021;138:281-283; Am J Obstet

Gynecol 2021;225:303.e1-17; N Engl J

Med 2021;384:2273-2282; Breastfeed

Med 2021;16:697-701; Breastfeed Med

2021;16:702-709]

“Dissemination of this safety and effi -

cacy data in a timely manner is the key to

increasing vaccine uptake in these populations,” the researchers said.

9

10

DOCTOR | NOVEMBER ISSUE

COVID-19 EXTRA

Autism risk in children not heightened

by COVID-19 exposure

JAIRIA DELA CRUZ

Children born during the COVID-19

pandemic or to mothers with history of prenatal SARS-CoV-2 infection are not at increased risk of autism

compared with their counterparts who

were born before the pandemic or have

no exposure to maternal SARS-CoV-2

infection, as reported in a cohort study.

“We evaluated neurodevelopmental

risk of children … using the M-CHAT-R, a

screening tool widely used for clinical and

research purposes, in a demographically

diverse sample in New York City, [US],”

the investigators said.

In a cohort of 2,049 children from

the COVID-19 Mother Baby Outcomes

(COMBO) Initiative, M-CHAT-R scores

at 16–30 months were extracted from

the electronic health records of 1,664

children (COMBO-EHR cohort). For the

remaining 385 children, M-CHAT-R was

administered prospectively at 18 months

for (COMBO-RSCH cohort).

“We found no increase in positive

screening rates for autism for children

born during the pandemic,” the investigators said.

M-CHAT-R positive screenings did

not signifi cantly diff er between children

born during and those born before the

pandemic both in the COMBO-EHR

cohort (23.2 percent vs 22.6 percent;

adjusted odds ratio [aOR], 0.75, 95 percent confi dence interval [CI], 0.52–1.08;

p=0.12) and the COMBO-RSCH cohort

(17.0 percent vs 13.5 percent; aOR,

1.40, 95 percent CI, 0.66–3.23; p=0.40).

[JAMA Netw Open 2024;7:e2435005]

“Surprisingly, we found that prenatal

maternal SARS-CoV-2 infection was associated with lower rates of positive autism screenings,” noted the investigators.

M-CHAT-R positivity rates were signifi cantly lower among children with vs

without prenatal exposure to maternal

SARS-CoV-2 infection in the COMBO-EHR cohort (12.3 percent vs 24

percent; aOR, 0.40, 95 percent CI,

0.22–0.68; p=0.001). However, in the

COMBO-RSCH cohort, the diff erence in

M-CHAT-R positivity did not reach statistical signifi cance, although the rates

were still lower among the exposed children (12.9 percent vs 19.9 percent; aOR,

0.51, 95 percent CI, 0.24–1.04; p=0.07).

Evidence suggests that SARS-CoV-2

may contribute to maternal immune activation, which has potential implications

for child neurodevelopment, through

temporary cytokine fl uctuations during

pregnancy. The fi ndings of the present

study are consistent with those of other

studies showing null or limited associ-

“Surprisingly, we found

that prenatal maternal

SARS-CoV-2 infection

was associated with

lower rates of positive

autism screenings”

11

DOCTOR | NOVEMBER ISSUE

COVID-19 EXTRA

ations between prenatal SARS-CoV-2

exposure and child neurodevelopment,

according to the investigators, who

nevertheless acknowledged that the

studies, along with the present, mostly involved participants with mild illness.

[Front Pediatr 2023;11:1277697; JAMA

Netw Open 2023;6:e234415; JAMA Pediatr 2022;176:e215563; JAMA Netw

Open 2023;6:e237396; BMC Pediatr

2022;22:319]

“We suspect that having COVID

during pregnancy may have infl uenced

parents’ assessment of their child’s behaviours, [while] parents who did not

have COVID may have experienced higher stress—due to the constant worry of

getting sick and the vigilance around preventing infection—and may have been

more likely to report concerning child behaviours,” explained senior investigator

Professor Dani Dumitriu from the Columbia University Irving Medical Center, New

York, New York, US.

Fears abated

Dumitriu acknowledged the ongoing

prevalence of COVID-19 and highlighted

the positive implications of the fi ndings,

stating that knowing that COVID-19

exposure in utero does not appear to

heighten autism risk can be a signifi cant

weight off pregnant people’s minds.

“Autism risk is known to increase

with virtually any kind of insult to mothers

during pregnancy, including infection and

stress. The scale of the COVID pandemic had paediatricians, researchers, and

developmental scientists worried that we

would see an uptick in autism rates. But

reassuringly, we did not fi nd any indication

of such an increase in our study,” she said.

“There has been broad

speculation about how

the COVID generation is

developing, and this study

gives us the fi rst glimmer

of an answer with respect

to autism risk”

Not out of the woods yet

Despite the lack of early indicators of autism, the possibility of other

issues emerging later cannot be entirely ruled out, according to Dumitriu

and colleagues. For one, the social and

economic impact of the COVID-19 pandemic may have long-term eff ects on the

development of pandemic-born children.

Furthermore, previous research suggests

a link between higher maternal stress

during pregnancy and lower educational

attainment in children. [Child Dev Perspect 2020;14:236-243; JAMA Psychiatry 2022;79:1040-1045; J Hum Resour

2016;51:523-555]

Also, Dumitriu acknowledged the

limitation of using the M-CHAT-R, stating that the study focused on autism risk

screening, without follow-up of actual diagnoses.

“It’s too early to have defi nitive diagnostic numbers. But this [M-CHAT-R]

screener is predictive, and it’s not showing that prenatal exposure to COVID or

the pandemic increases the likelihood of

autism,” she continued. “There has been

broad speculation about how the COVID

generation is developing, and this study

gives us the fi rst glimmer of an answer

with respect to autism risk.”

EADV 2024

September 25-28

Phototherapy for psoriasis at home as good as

in the offi ce

12

DOCTOR | NOVEMBER ISSUE

ELVIRA MANZANO

Narrowband ultraviolet B (NB-UVB)

phototherapy or light therapy

performed at home is as good

as one done in the doctor’s offi ce in patients with plaque and guttate psoriasis,

as shown in the randomized Light Treatment Eff ectiveness (LITE) trial presented

at EADV 2024.

At 12 weeks, more patients receiving

home than offi ce phototherapy achieved

clear/almost clear skin (32.8 percent vs

25.6 percent; p<0.001) as refl ected by a

PGA* score of ≤1.

Similarly, there were more patients

treated with home- vs offi ce-based phototherapy achieving a DLQI** score ≤5

(no-to-small eff ect on patients’ life) at

52.4 percent vs 33.6 percent (p<0.001).

The same benefi ts were observed across

all Fitzpatrick *** skin types (1-6). [JAMA

Dermatol 2024; 25:e243897]

Despite dramatic advances in psoriasis treatment, patients are clamouring for

therapeutic control because medications

are only partially eff ective, lose their effect over time, or are discontinued due to

adverse eff ects like infection, poor adherence, or a multitude of access and cost

issues. Many still prefer nonpharmaceutical approaches. [Cutis 2022;110:E3-E7]

“Home phototherapy is patient-preferred but currently has very limited

clinical data,” said study author Dr Joel

Gelfand from the Psoriasis and Phototherapy Treatment Center at the UniverNB-UVB phototherapy uses wavelengths of 308–312 nm and works by

suppressing the cutaneous cell-mediated immune response. It has been shown

to be an eff ective and clinically tolerable

treatment for a range of infl ammatory

dermatoses, including psoriasis. [Cureus

2021; 13: e19182; J Am Acad Dermatol

2019;81:775-804]

An option with less burden

The current study lends credence to

previous trials showing that at-home NBUVB phototherapy was at least as eff ective and safe as NB-UVB phototherapy

in the outpatient clinic setting for mildto-severe psoriasis. [Ont Health Technol Assess Ser 2020;20:1-134; BMJ

2010;340:c1490]

According to Gelfand, as traditional

clinic-based phototherapy is time-consuming, expensive, and inconvenient

for patients, home phototherapy off ers

an alternative option with less burden to

patients.

*PGA = Physician Global Assessment

**DLQI = Dermatology Life Quality Index

***Method to classify skin colour and cancer risk

sity of Pennsylvania, Philadelphia, US at

EADV 2024. “Our fi ndings support the

use of home phototherapy as a fi rst-line

treatment option for psoriasis. Eff orts are

needed to make home and offi ce phototherapy more available to patients.”

Looking into the LITE

population

The study included 783 patients enrolled from 42 dermatology clinics in the

US from March 2019 to December 2023.

The mean age of the patients was 48

years, and 48 percent were female.

Researchers compared 12-week

treatment with NB-UVB phototherapy at

home (n=393 patients) vs at the doctor’s

offi ce (n=390 patients). The mean PGA

and DLQI scores at baseline were 2.7

and 12.2, respectively. Nearly 45 percent

of patients had skin types 1-2, 44.7 percent had skin types 3-4, while 10.6 percent had skin types 5-6. About 11.9 percent were already on systemic treatment.

A higher percentage of patients were

adherent to home than offi ce-based

phototherapy (51.4 per cent vs 15.9 per

cent; p<0.001).

Gelfand, however, acknowledged

that because LITE was an open-label trial

with a pragmatic design, some outcome

data were missing. “Additionally, the cost

of the home-based phototherapy equipment used in the study was $6,040.88

and mostly covered by Medicare, but

direct costs to patients may have varied

depending on an individual’s insurance

plan,” he shared.

DOCTOR | NOVEMBER ISSUE

13

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

JAIRIA DELA CRUZ

Deucravacitinib, an oral selective inhibitor of tyrosine kinase 2 (TYK2),

shows promise in the treatment of

lichen planopilaris (LPP), with substantial

reductions in disease activity, according

to an interim analysis of an open-label,

single-arm trial.

The Lichen Planopilaris Activity Index (LPPAI) score decreased from 3.8

at baseline to 1.6 at week 12 and 1.2

at week 16, corresponding to about a

60-percent and 70-percent improvement, respectively, reported principal

investigator Dr Aaron Mangold from the

Mayo Clinic Dermatology in Scottsdale,

Arizona, US. [EADV 2024, abstract 7862]

In addition, Physician Global Assessment (PGA) 0–3 response* signifi cantly

increased, with the proportion of patients achieving a greater than 50-percent improvement rising from 20 percent

at week 2 to 80 percent at week 12

(p=0.024) and 100 percent at week 16

(p=0.005).

Looking at parallel responses in LPPAI and Itch Numerical Rating Scale

(NRS), Mangold noted a distinct pattern

in LPP. Unlike atopic dermatitis, where

itch relief often precedes clinical improvement, LPP patients experienced a

more rapid improvement in their clinical

symptoms before noticing a signifi cant

reduction in itch.

“The average time to greater than

50-percent improvement in LPPAI was

about 5.8 weeks, whereas the average

time to greater than 50-percent reduction in Itch NRS was 11.1 weeks,” he

said.

Mangold presented a series of sideby-side patient photos, comparing baseline and week 24 conditions. He pointed

to signifi cant reductions in perifollicular

infl ammation, scaling, and erythema following treatment with deucravacitinib. Notably, in one patient, response was maintained even after discontinuing therapy.

“We didn’t see any

serious treatmentemergent adverse

events (TEAEs) or

TEAEs leading to

discontinuation”

Safety

“Deucravacitinib was well tolerated,”

Mangold said. “We didn’t see any serious treatment-emergent adverse events

(TEAEs) or TEAEs leading to discontinuation.”

A total of 13 mild drug-related AEs

occurred, with the most common being

acne (70 percent). Other less common

AEs were hand dermatitis, rash around

neck/ears/face, and cold or fl u. Of these

AEs, 83.3 percent improved or resolved

upon cessation of therapy.

TYK2 inhibitor looks good for lichen planopilaris

The interim analysis included 10

heavily pretreated adult patients (mean

age 61.4 years, 70 percent female, 100

percent White) with biopsy-proven active

LPP (median disease duration 6.4 years).

The mean number of prior treatments

was 4.1, while the mean number of systemic therapies was 1.7. Six patients had

received intralesional injections, and one

patient had skin-directed therapy.

Deucravacitinib was given at 6 mg

twice daily for 24 weeks. A washout period of 2 weeks for topical and 4 weeks or

longer for systemic agents was required.

Effi cacy and safety evaluations were

conducted every 4 weeks through week

24. An additional follow-up of 4 weeks

post-treatment was conducted.

“Additional controlled studies are

needed to assess the safety and effi cacy

of deucravacitinib in LPP,” according to

Mangold, who shared news of pending

molecular data from bulk spatial and single-cell sequencing.

*PGA response: grade 3 (50 percent to 75 percent

improvement), grade 2 (75 percent to 90 percent improvement), grade one (>90 percent improvement), and

grade 0 (100 percent improvement)

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Upadacitinib superior to dupilumab in patients

with moderate-to-severe AD

DOCTOR | NOVEMBER ISSUE

ELAINE SOLIVEN

Treatment with upadacitinib demonstrated superior effi cacy in achieving near-complete skin clearance

and little to no itch at 16 weeks compared

with dupilumab among adolescents and

adults with moderate-to-severe atopic

dermatitis (AD), according to the LEVEL

UP study presented at EADV 2024.

At week 16, signifi cantly more patients in the upadacitinib group achieved

the primary composite endpoint of

≥90-percent reduction in Eczema Area

and Severity Index (EASI90) and Worst

Pruritus-Numerical Rating Scale of 0 or 1

(WP-NRS 0/1) than the dupilumab group

(19.9 percent vs 8.9 percent; p<0.0001).

[EADV 2024, abstract 5385]

Similarly, upadacitinib showed superiority over dupilumab for all ranked secondary endpoints, particularly in achieving rapid onset of skin clearance (EASI90:

45.3 percent vs 26.3 percent; p<0.0001)

and little to no itch (WP-NRS 0/1: 34.4

percent vs 18.8 percent; p<0.0001).

Of note, “the separation in the response to upadacitinib vs dupilumab

was seen as early as week 1 for itching

and week 2 for skin clearance,” said Dr

Kilian Eyerich from the Department of

Dermatology at George Washington University School of Medicine in Washington, DC, US, who presented the study

on behalf of the investigators.

“Overall, the LEVEL UP study met the

primary and all ranked secondary endpoints,” Eyerich noted.

The study is a head-to-head phase

IIIb/IV trial, which analysed 920 patients

(117 adolescents and 803 adults) with

moderate-to-severe AD who had an

inadequate response to systemic therapy or when the use of those therapies

was inadvisable. Participants were randomized 1:1 to either upadacitinib 15

mg once daily as the starting dose, with

a dose escalation to 30 mg once daily

based on clinical response (n=458), or

dupilumab per its label dose (n=462) for

16 weeks.

A cumulative dose escalation rate of

nearly 70 percent was observed among

patients receiving upadacitinib at week

12. Eyerich noted that 52 percent of patients treated with upadacitinib achieved

the primary endpoint without increasing

their dose, and 48 percent of patients

who were escalated to 30 mg also

achieved this outcome.

“The separation

in the response

to upadacitinib vs

dupilumab was seen

as early as week 1

for itching and week 2

for skin clearance”

“During the 16-week

treatment period,

the safety fi ndings

for upadacitinib and

dupilumab were

consistent with their

known safety profi les,

with no new safety

signals identifi ed”

However, in terms of safety, adverse events (AEs) occurred more frequently in the upadacitinib arm vs the

dupilumab arm (65.3 percent vs 52.7

percent), which was expected, said Eyerich.

The rates of serious

AEs (0.9 percent for both)

and AEs leading to treatment discontinuation (2

percent vs 1.3 percent)

were similar between

the upadacitinib and

dupilumab arms, with

no deaths reported in

either treatment arm.

In addition, no malignancies, adjudicated major adverse cardiac events and

venous thromboembolic events, or active tuberculosis were reported.

During the 16-week treatment period, the safety fi ndings for upadacitinib

and dupilumab were consistent with

their known safety profi les, with no new

safety signals identifi ed, Eyerich noted.

14

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

DOCTOR | NOVEMBER ISSUE

15

Long-term secukinumab works

for kids with chronic plaque

psoriasis

STEPHEN PADILLA

L ong-term treatment with secukinumab, either at low or high dose,

results in sustained effi cacy and

better health-related quality of life up to

4 years in children and adolescents with

moderate-to-severe chronic plaque psoriasis, as shown in a phase III study presented at EADV 2024.

With regard to safety, no new signals

have been observed, and both doses of

secukinumab are well tolerated by patients.

“Growth and development data did

not show any notable adverse eff ects

with secukinumab treatment in the paediatric population,” said lead author Dr

Kulli Kingo from Tartu University Hospital

and University of Tartu in Tartu, Estonia.

Kingo and colleagues conducted

this randomized phase III, open-label

trial in 84 paediatric patients aged 6 to

<18 years, who were randomly assigned

to receive either low-dose (75/75/150

mg; n=42) or high-dose (75/150/300

mg; n=42) secukinumab based on their

weight (<25 kg, 25 to <50 kg, or ≥50

kg) and disease severity (moderate or

severe).

Safety

No new safety signals were identifi ed in this paediatric population with

long-term exposure to secukinumab (approximately 313.9 patient-years). Both

dose groups also had similar incidence

of treatment-emergent adverse events

(low dose: 78.6 percent; high dose: 83.3

percent).

The most common safety concerns

were infections and infestations, gastrointestinal disorders, and skin and

subcutaneous tissue disorders. Moreover, the most frequent adverse events

were acne, COVID-19, and nasopharyngitis.

“Secukinumab did not have any adverse eff ect on the growth and development of patients or on their sexual maturation, as evaluated by Tanner score,”

Kingo said.

In addition, antidrug antibody (ADA)

development with secukinumab therapy for 208 weeks was low, with seven patients (8.3 percent) having positive treatment-emergent ADAs and six

showing positive ADAs only during follow-up.

“Secukinumab is a fully human

monoclonal antibody that selectively

neutralizes interleukin-17A, a key cytokine involved in the pathogenesis of

plaque psoriasis,” Kingo said. [N Engl J

Med 2014;371:326-338]

“The effi cacy and safety of secukinumab up to week 52 have been reported previously for the present pivotal

phase III study in children and adolescents with moderate-to-severe chronic

plaque psoriasis,” she added. [Paediatr

Drugs 2022;24:377-387]

The trial had three phases, namely

screening (up to 4 weeks), treatment

(208 weeks), and post-treatment follow-up (16 weeks).

Kingo and her team then assessed

the long-term effi cacy of secukinumab

via Psoriasis Area and Severity Index

(PASI) 75/90/100 response, Investigator’s Global Assessment modifi ed

2011 (IGA mod 2011) 0/1 response,

and PASI score. They also evaluated

the Children’s Dermatology Life Quality

Index (CDLQI) 0/1 response, impact of

treatment on physical development, and

safety over 4 years.

Of the patients, 67 (79.8 percent)

completed the treatment. Both treatment groups maintained high PASI

75/90/100 and IGA 0/1 responses from

week 12 until end of treatment. [EADV

2024, abstract 5915]

At week 208, patients on secukinumab demonstrated sustained PASI

75/90/100 (low dose: 96.3 percent/88.9

percent/51.9 percent; high dose: 87.9

percent/81.8 percent/51.9 percent) and

IGA mod 2011 0/1 responses (low dose:

85.2 percent; high dose: 84.8 percent).

From week 12 to week 208, both

treatment groups had low mean PASI

score. At week 208, the mean percentage change in PASI scores from baseline was ?95.7 percent (mean absolute

score 0.76) with low-dose secukinumab

and ?94.5 percent (mean absolute score

1.07) with high-dose secukinumab.

Additionally, both the low- and highdose groups showed high CDLQI 0/1

response from week 12 up to week 208

(low dose: 75 percent; high dose: 88.2

percent).

DOCTOR | NOVEMBER ISSUE

16

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Real-world study supports tralokinumab

for diffi cult-to-treat AD

AUDREY ABELLA

I

nterim data from the real-world

TRACE study confi rm the benefi ts of

the high-affi nity monoclonal antibody

tralokinumab for individuals with moderate-to-severe head and neck atopic dermatitis (H&N AD) after up to 9 months of

treatment.

Eighty percent of the study participants had H&N AD at baseline. By month

9, only half of these patients had H&N

involvement, noted Dr April Armstrong

from the University of California Los Angeles in the US. This was a notable drop

from the 67 percent reported at month 3.

A similar pattern was also observed at

9 months among participants who were

dupilumab-na?ve and dupilumab-experienced (50 percent and 57 percent, respectively). [EADV 2024, abstract 8084]

Other parameters

In patients with baseline H&N AD,

only 1.4 percent had an Investigator’s

Global Assessment (IGA) score of 0/1 at

baseline, which corresponds to clear/almost clear skin. By month 3, a third had

achieved this endpoint. This improved to

48 percent by month 6 and to 57 percent

by month 9.

This, in turn, was met with consistent drops in the proportions of participants with an IGA score of 4 or severe

disease at baseline, dropping substantially from 38 percent to 5 percent at 3

months and 3 percent at 6 months. By

month 9, this was down to 2 percent,

corresponding numerically to just two

patients.

For those with a baseline IGA ≥2,

46 percent achieved ≥2-point improvement at 3 months. This jumped to 59

percent at 6 months and 72 percent at

9 months.

Among patients with baseline DLQI*

≥6, the percentages of participants

achieving ≥6-point reduction in DLQI at

3, 6, and 9 months were 58, 64, and

74 percent, respectively. According to

Armstrong, the DLQI reductions denoted clinically meaningful improvement in

quality of life (QoL).

Patient-reported eczema control

also improved, as refl ected by the fraction of participants with RECAP** <6 by

month 9 (45 percent). “RECAP <6 identifi ed patients whose AD is considered

completely controlled (RECAP 0–1) or

mostly controlled (RECAP 2–5),” Armstrong explained.

Mean Peak Pruritus NRS*** also

consistently improved across all timepoints (from 6.4 at baseline to 4.2, 3.5,

and 3.3 at 3, 6, and 9 months, respectively), as did mean Sleep-NRS (from

5.2 at baseline to 2.8, 2.3, and 2.3).

Overall, response rates and improvements were consistent irrespective of

treatment history, Armstrong noted.

Signifi cant QoL burden

About three-quarters of patients

with moderate-to-severe AD have

H&N involvement. [J Am Acad Dermatol 2023;89:519-528] “AD with involvement of H&N, more than other

body regions, is associated with social embarrassment, stigmatization,

and a significant negative impact on

patients’ QoL and mental health,”

stressed Armstrong. “Patients can be

quite dissatisfied if those areas are not

treated well.”

The team thus set out to evaluate tralokinumab in this single-cohort

study of tralokinumab-na?ve adults

with AD. At data cutoff for this interim analysis, the full analysis set comprised 824 patients at baseline, and

668, 331, and 143 patients at months

3, 6, and 9.

Of the 655 AD patients who had

H&N (face, scalp, and/or neck) involvement, 154 were dupilumab-experienced, while the rest were dupilumab-na?ve. Mean age was 42.1 years, 53

percent were men, and mean disease

duration was 20.6 years. A third had

IGA 4.

“[Taken together, the fi ndings show

that] up to 9 months of tralokinumab

treatment in a real-world setting reduced H&N involvement and improved

disease severity and QoL in patients

with AD in the diffi cult-to-treat H&N

area. All improvements were similar regardless of prior dupilumab use,” noted

Armstrong.

In a separate news release, LEO

Pharma Chief Development Officer

Kreesten Meldgaard Madsen said,

“We are particularly encouraged to see

treatment with [tralokinumab] leading

to such positive real-world outcomes

in a challenging region of the body,

regardless of previous biologic treatment.”

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Patients with scalp psoriasis experience

fi rst-hand improvements in itch, fl aking,

pain from deucravacitinib

MIKE NG

An interim analysis of patient-reported outcomes from the phase IIIb/

IV PSORIATYK SCALP trial shows

that treatment with the allosteric tyrosine

kinase 2 (TYK2) inhibitor deucravacitinib

signifi cantly reduces itch, fl aking, and pain

specifi c to the scalp, as well as wholebody itch, vs placebo at week 16 in patients with moderate-to-severe scalp psoriasis, including those with less extensive

body surface area (BSA) involvement.

On an 11-point numeric rating scale

(NRS) from 0 to 10, the adjusted mean

change from baseline to week 16 in

scalp-specifi c itch, a key secondary

endpoint, was ?3.2 for deucravacitinib

vs ?0.7 for placebo (p<0.0001). [EADV

2024, abstract 5390]

For exploratory endpoints, signifi -

cantly greater improvements on the

NRS for scalp-specifi c fl aking (?3.9 vs

?1; p<0.0001), scalp-specifi c pain (?2.1

vs ?0.1; p<0.0001), and whole-body

itch (?2.9 vs ?0.4; p<0.0001) were reported at week 16 among patients

treated with deucravacitinib vs those

receiving placebo.

Unlike the prior phase III POETYK

trials, patients with ≥3 percent BSA involvement could enrol (vs ≥10 percent in

POETYK), provided that the mandatory

scalp involvement criteria were fulfi lled.

[J Am Acad Dermatol 2023;88:29-39;

J Am Acad Dermatol 2023;88:40-51]

“This is a diff erent population, probably

one with a phenotype primarily localized

to the scalp,” said Professor Diamant

Tha?i from the Institute of Infl ammation

Medicine, University of Lübeck in Lübeck, Germany, during his presentation

at EADV 2024.

“These patients in many countries do

not fulfi l the criteria for systemic treatment.

I think that’s going to change because

they suff er just as much as other patients

and have a high need for treatment as

well,” said Tha?i, highlighting the implications of less extensive overall psoriasis

as part of PSORIATYK SCALP’s eligibility

criteria.

Scalp matters

PSORIATYK SCALP is an ongoing

trial that includes adults with moderate-to-severe scalp psoriasis, defi ned

as a scalp-specifi c Physician Global Assessment score ≥3, a scalp surface area

involvement ≥20 percent, and a Psoriasis

Scalp Severity Index score ≥12. Patients

had to have evidence of plaque psoriasis in a nonscalp area and be candidates

for systemic therapy or phototherapy. All

patients had either failed to respond to or

were intolerant of ≥1 topical therapy for

scalp psoriasis.

The scalp-specifi c trial randomized

154 patients 2:1 to receive either deucravacitinib 6 mg or placebo, administered orally once daily.

“Scalp matters,” Tha?i repeated three

times during the presentation. “If you see

how the patients were reporting their

scalp-specifi c itch at baseline in the trial,

it was 6.4 on average out of 10. This is a

lot.” Other patient-reported assessments

at baseline on the NRS were 6.9 for

scalp-specifi c fl aking, 4.2 for scalp-specifi c pain, and 5.8 for whole-body itch.

Response rates, based on a minimum

clinically important diff erence (MCID) of

≥4-point improvement, were also compared between patients treated with

deucravacitinib and placebo to provide a

more clinically relevant interpretation. For

each NRS measure, the MCID response

rates were signifi cantly higher in the deucravacitinib arm vs the placebo arm, with

the greatest between-arm diff erence observed for scalp-specifi c fl aking (53.4 percent vs 19.6 percent; p<0.0001).

“We know that at week 16, that is

not a plateau with the TYK2 inhibitor. In

the upcoming 52-week results that we’re

going to present, we will likely see even

higher response rates, which I expect,”

concluded Tha?i.

DOCTOR | NOVEMBER ISSUE

17

DOCTOR | NOVEMBER ISSUE

18

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Psoriasis patients with overweight, obesity may

need higher vunakizumab doses

4.8), and sPGA 0/1 (OR, 3.1, 95 percent

CI, 1.8–5.4).

These fi ndings were further confi rmed in analyses of the longer-term

52-week data, serum vunakizumab

concentrations, and subgroup defi ned by body weight (<90 vs ≥90

kg), according to Li.

As for safety, treatment-emergent

adverse events occurred with similar frequency across BMI groups, he added.

In conclusion, Li emphasized that

higher BMI and greater body weight

negatively infl uenced response rates to

vunakizumab, which persisted throughout the 52-week treatment period.

JAIRIA DELA CRUZ

I

n the treatment of moderate-to-severe

psoriasis, patients with overweight or

obesity appear to have a diminished response to vunakizumab compared with

those who have lower BMIs, according

to a post hoc subgroup analysis of a

phase III trial.

Response rates to vunakizumab 240

mg at the 12-week follow-up, decreased

as BMI increased, reported study author

Prof Linfeng Li from Beijing Friendship

Hospital, Beijing, China.

Li noted that vunakizumab was administered every 2 weeks for three doses during the induction phase, followed

by a maintenance dose every 4 weeks

through week 52.

At week 12, Psoriasis Area and Severity Index (PASI) 90 response was seen

in 84.9 percent of patients with normal

weight or lower (BMI <24 kg/m2

), 77.6

percent of those with overweight (BMI

24–27.9 kg/m2

), and 66.7 percent of those

with obesity (BMI ≥28 kg/m2

). The median

time to achieve PASI 90 was longest in the

obesity group at 71.5 days as opposed

to 57 days in the normal weight or underweight group and 58 days in the overweight group. [EADV 2024, abstract 3686]

Results for the Static Physician’s

Global Assessment (sPGA) 0/1 response

followed a similar trend, with rates of

83.2 percent in the normal weight or underweight group, 76 percent in the overweight group, and 61.6 percent in the

obesity group. The same held true for

PASI 75 (97.2 percent, 95.1 percent, and

85.9 percent, respectively), PASI 100

(45.8 percent, 39.9 percent, and 23.2

percent, respectively) and sPGA 0 (46.9

percent, 42.6 percent, and 24.2 percent,

respectively) responses.

Compared with normal weight or underweight, obesity was associated with

greater odds of having lower response to

PASI 90 (odds ratio [OR], 2.8, 95 percent

confi dence interval [CI], 1.6–5.0), PASI

75 (OR, 5.7, 95 percent CI, 2.1–15.8),

PASI 100 (OR, 2.8, 95 percent CI, 1.6–

“Adjusting the dosage

based on BMI and body

weight could potentially

enhance effi cacy and

optimize patient outcomes”

“The observed decrease in vunakizumab concentration with increasing

BMI suggests that standard dosing may

be suboptimal for patients with overweight or obesity. Adjusting the dosage

based on BMI and body weight could

potentially enhance effi cacy and optimize

patient outcomes,” he said.

The analysis included 461 patients

(mean age 41.7 years, 76.4 percent

male, mean Body Surface Area 34.45

percent, mean PASI score 22.23) with

moderate-to-severe psoriasis who received vunakizumab. Of these, 179

patients were in the normal weight or

underweight group, 183 were in the

overweight group, and 99 were in the

obese group.

DOCTOR | NOVEMBER ISSUE

19

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

DISCREET highlights apremilast potential

for genital psoriasis

AUDREY ABELLA

I

ndividuals with psoriasis creeping into

their intimate areas may fi nd relief from

apremilast, as shown by the week-32

improvements in multiple disease parameters in the phase III DISCREET study.

An oral phosphodiesterase-4 inhibitor, apremilast has been given the FDA

nod for the treatment of plaque psoriasis.

However, its potential across the disease

spectrum – including genital psoriasis –

remains unclear.

“Genital psoriasis is common in patients with psoriasis and carries a signifi cant burden,” said Dr Joseph Merola

from the UT Southwestern Medical Center, Dallas, Texas, US, at EADV 2024.

About two-thirds of patients with psoriasis experience genital psoriasis over

the course of their disease, but it is often

overlooked and undertreated.

The team evaluated 289 patients

with moderate-to-severe (modifi ed sPGA-G* [or genital PGA] score ≥3) genital

psoriasis. They were randomized 1:1 to

apremilast 30 mg BID or placebo for 16

weeks. After which, 229 patients (mean

age 45.2 years, 70.3 percent men) entered an extension period wherein all

received apremilast for an additional 16

weeks. Eighty-six percent had a modifi ed genital PGA score of 3, while 88.6

percent had an overall sPGA score of 3.

[EADV 2024, abstract 3339]

Skin, genital psoriasis

symptoms

Week 16 saw better modifi ed genital PGA response rates (score of 0/1

with a ≥2-point reduction from baseline)

with apremilast vs placebo (38.7 percent

vs 20.9 percent). The rate was generally maintained in the apremilast arm by

week 32 (40.3 percent); in the placebo

arm, the rate rose during the extension

phase, reaching 51.8 percent at week

32. This means that up to half of treated patients achieved clear/almost clear

genital skin with the transition from placebo to active treatment, Merola noted.

A similar pattern was seen in overall sPGA responses (score of 0/1 with a

≥2-point reduction from baseline) over

time. In the apremilast arm, responses improved slightly from week 16 to

32 (from 22.7 percent to 30.3 percent).

Among placebo recipients, there was a

marked improvement between the two

timepoints (from 8.2 percent to 33.6 percent).

Of note, 28.2 percent and 31.9 percent of participants in the respective

apremilast and placebo arms achieved

a modifi ed genital PGA of 0 by week

32. The corresponding proportions of

participants achieving an overall sPGA

of 0 were 14.6 percent and 18.1 percent. These suggest that up to a third

of patients achieved complete genital

skin clearance, while nearly 20 percent

achieved full skin clearance at week 32,

noted Merola.

For genital itch response rates, the

proportion of participants achieving GPINRS** responses in the apremilast arm

was sustained between weeks 16 and

32 (from 44.6 percent to 46.5 percent).

A slightly diff erent pattern was seen in

the placebo arm – the rate jumped from

18.9 percent at week 16 to 57.9 percent

by week 24 but dropped to 48.4 percent

by week 32. Nonetheless, Merola noted

that these rates translated to meaningful

improvements in genital itch symptoms.

Other measures that improved with

apremilast were BSA*** and GPSS#

.

Among those who received apremilast

across the entire study, mean percent

change in BSA from baseline improved

from –32.8 percent at week 16 to –45.9

percent at week 32. This trend was similarly seen for GPSS (from –44.6 percent

to –51.4 percent). The improvements

were greater in the placebo arm following

the shift to apremilast (from –8 percent to

–49.6 percent [BSA] and from –4 percent

to –55.5 percent [GPSS]).

QoL, sexual health, safety

“Genital psoriasis is associated with

painful and bothersome signs and symptoms, impairs quality of life (QoL), and

negatively impacts sexual health,” said

Merola. In DISCREET, QoL and sexual

health improvements accompanied the

skin improvements.

These were evidenced by the mean

percent changes in DLQI## in the apremilast arm from baseline to week 16 (–38.2

percent), further improving through week

32 (–48.6 percent). With placebo, the

corresponding week-16 reduction was

only 12.3 percent, but with the transition to apremilast, this dropped further to

about 56 percent.

A similar pattern was seen for DLQI

Question 9 (DLQI-Q9), a question asking

about sexual diffi culties arising from the

skin issues. The mean percent change

from baseline was nearly 60 percent by

week 32 across both apremilast and placebo arms.

Moreover, about 30 percent of participants achieved a DLQI score of 0/1,

while nearly 90 percent achieved a

DLQI-Q9 response of 0/1 or ‘no impact’

by week 32.

*sPGA-G: static Physician Global Assessment of

Genitalia

**GPI-NRS: Genital Psoriasis Itch Numeric Rating

Scale; ≥4 point reduction from baseline for patients

with a baseline score of ≥4

***BSA: Body surface area

#

GPSS: Genital Psoriasis Symptoms Scale

##DLQI: Dermatology Life Quality Index

DOCTOR | NOVEMBER ISSUE

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Remibrutinib off ers rapid, sustained symptom

relief in patients with CSU

ELAINE SOLIVEN

Treatment with remibrutinib, an

oral, highly selective Bruton’s

tyrosine kinase inhibitor, led to

rapid symptom improvement that lasted for 52 weeks in patients with chronic

spontaneous urticaria (CSU), according

to the pivotal phase III REMIX-1 and -2

studies presented at EADV 2024.

As early as week 1, patients who received remibrutinib achieved signifi cant

improvements in weekly Urticaria Activity Score (UAS7) compared with those

treated with placebo in REMIX-1 (mean

change from baseline [CFB], -11.3 percent vs -4 percent; p<0.001) and REMIX-2 (mean CFB, -11.3 percent vs

-2.9 percent; p<0.001).

There was also a signifi cantly higher percentage of patients on remibrutinib vs those on placebo who achieved

well-controlled urticaria, as indicated by

UAS7 score of ≤6 (UAS7≤6), at week 1

in both studies (12.6 percent vs 0.7 percent [REMIX-1] and 10.8 percent vs 0.7

percent [REMIX-2]; p=0.001 for both).

In addition, signifi cantly more remibrutinib-treated patients were completely

free of itch and hives (UAS7=0) as early as week 2 (16.8 percent vs 1.3

percent; [REMIX-1] and 15.5

percent vs 1.3 percent

[REMIX-2]; p<0.001 for

both) than the placebo-treated patients.

In both REMIX studies, signifi cant improvements with remibrutinib

were sustained through 52

weeks, particularly in UAS7 and

UAS7≤6 among patients who initially

received and continued treatment with

remibrutinib.

-22.4 percent [REMIX-2]), which were

similar to the trend observed with those

taking remibrutinib initially.

Moreover, 64.1 percent and 62.4

percent of placebo-remibrutinib recipients achieved UAS7≤6 and 42.7 percent

and 42.2 percent achieved UAS7=0 at

week 52 in both REMIX-1 and -2 studies, respectively. These results were also

consistent with those observed in the remibrutinib group.

“Taken together, patients who transitioned to remibrutinib from placebo at

week 24 achieved fast and sustained reductions in UAS7 until study end,” said

Giménez-Arnau.

Pooled safety endpoints

In a pooled safety analysis of REMIX-1 and -2 studies, the rates of adverse events (AEs; 64.9 percent vs 64.7

percent), serious AEs (3.3 percent vs 2.3

percent), and treatment discontinuation

due to AEs (2.8 percent vs 2.9 percent)

were comparable between the remibrutinib and placebo arms during the double-blind treatment period.

Giménez-Arnau noted that exposure-adjusted incidence rates did not

increase with long-term treatment up to

week 52, and there were no serious AEs

associated with the study drug.

“Remibrutinib showed favourable

safety and tolerability up to 52 weeks

across both REMIX studies,” said

Giménez-Arnau.

“Overall, both phase III [REMIX-1 and

-2] studies in patients with CSU inadequately controlled by H1-antihistamines

showed fast improvements in UAS7 with

remibrutinib as early as week 1, with

continued improvement up to week 52

vs placebo,” concluded Giménez-Arnau.

“[With these results,] remibrutinib

has the potential to become a novel oral

treatment option that provides fast and

sustained symptom relief in patients with

CSU inadequately controlled by H1-antihistamines,” said lead author Professor

Ana Maria Giménez-Arnau from the Department of Dermatology at Hospital del

Mar and Research Institute and Universitat Pompeu Fabra, Barcelona, Spain.

REMIX-1 and -2 cohorts consisted of

470 (mean age 45 years, 68.3 percent

female) and 455 (mean age 41.7 years,

65.3 percent female) patients with CSU

(mean UAS7 of 30.3 and 30, respectively). The median duration of CSU was

6.6 years in REMIX-1 and 5.2 years in

REMIX-2. Participants were randomized

2:1 to receive remibrutinib 25 mg twice

daily (n=313 [REMIX-1] and n=300 [REMIX-2]) or placebo (n=157 and n=155,

respectively) for a 24-week double-blind

treatment period, followed by a 28-week

open-label treatment period. By week

24, all placebo recipients were transitioned to remibrutinib (placebo-remibrutinib group). [EADV 2024, abstract 5727]

Among placebo recipients who

switched to remibrutinib, signifi cant improvements in UAS7 were observed at

52 weeks (mean CFB, -23 percent [REMIX-1] and

20

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

DOCTOR | NOVEMBER ISSUE

33

Ebdarokimab works well for plaque psoriasis

STEPHEN PADILLA

A recent study has shown the safety and effi cacy of ebdarokimab

(AK 101) in the treatment of patients with plaque psoriasis, achieving

≥75-percent improvement in Psoriasis

Area and Severity Index (PASI 75) and

Static Physicians Global Assessment

(sPGA) 0/1 response.

“Ebdarokimab was generally safe and

well tolerated, with good improvements

in PASI 75 and sPGA 0/1 responses in

Chinese patients with moderate-to-severe plaque psoriasis,” said lead author

Dr Jianzhong Zhang from Peking University People’s Hospital, Beijing, China.

The fi ndings of this single-arm,

open-label, multicentre phase III trial were

presented at the recent EADV Congress

2024 in Amsterdam, the Netherlands.

Zhang and his team assessed the

long-term safety and effi cacy of ebdarokimab in 950 patients aged ≥18

years, who were divided into three

groups.

Group 1 had patients treated with

ebdarokimab in the previous 16-week

double-blind, placebo-controlled study,

who continued receiving the study drug

in the current analysis. They received the

135-mg dose at week 16, followed by

maintenance therapy every 12 weeks,

with follow-up until week 52.

Group 2 included patients from the

placebo group in the previous study. In the

current study, they received ebdarokimab

135 mg at week 16 or week 20, followed

by maintenance therapy every 12 weeks,

and follow-up until week 52.

Finally, the third group involved patients who directly participated in the

current study. They received the 135-mg

dose at week 0 or week 4, followed by

maintenance therapy every 12 weeks,

with follow-up until week 52.

Improvements

In group 1, 80.5 percent of patients

achieved PASI 75, while 66 percent

achieved sPGA 0/1 response. These

improvements persisted up to week 52.

[EADV 2024, abstract 982]

For patients in group 2, their PASI

score decreased after switching to ebdarokimab at week 16, indicating disease improvement. The rates of PASI 75

and sPGA 0/1 response were 81.4 percent and 71.1 percent, respectively, both

of which were maintained until week 52.

Finally, in group 3, 69.5 percent of

patients achieved PASI 75, and 59.1

percent had sPGA 0/1 response. These

rates were consistent with those from

group 1.

“All patients were followed up to

week 28 at least and showed a stable

long-term effi cacy,” Zhang said.

In terms of safety, most of the patients (n=788, 82.9 percent) experienced

at least one treatment-emergent adverse

event (TEAE), but roughly one in three

(33.1 percent) had TEAE related to ebdarokimab (TRAE).

Groups 1 and 2 had a slightly higher

TEAE incidence than group 3 (89.1 percent and 85.6 percent vs 79.3 percent),

while the incidence of TRAE was comparable among groups. Most of these

events were either mild or moderate in

severity.

However, 32 patients (3.4 percent)

had a serious adverse event, and one

(0.1 percent) died due to a traffi c accident, which was not related to the study

drug.

“AK 101 is a fully human monoclonal antibody targeting interleukin (IL)-12/

IL-23 pathway and specifi cally binds to

the P40 subunit of both IL-12 and IL-23,

resulting in inhibition of the signaling of

IL-12 and IL-23 cytokines,” Zhang said.

“IL-12 and IL-23 are two essential

cytokines involved in the immune-mediated infl ammatory disorders of psoriasis.

Anti-IL-12/IL-23 therapy has been developed for the treatment of psoriasis,” he

added.

21

DOCTOR | NOVEMBER ISSUE

22

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

AUDREY ABELLA

A post hoc analysis of a phase IV

study presented at EADV 2024

underscores the ability of the

fourth-generation retinoid trifarotene to

reduce atrophic acne scars across all

skin types, with a more profound eff ect

among individuals with higher baseline

acne and acne scarring severity.

“[In] acne patients, after putting out

the fi re and the acne is better, they are

worried about scarring and pigmentation,” said Dr Jerry Tan from the University of Western Ontario, Windsor, Ontario,

Canada. “Hence, we wanted to focus

on the eff ect of trifarotene, which has already shown effi cacy in phase III studies

of atrophic acne scars.”

“[In this study,] trifarotene continues

to demonstrate eff ectiveness as a treatment option for a broad spectrum of

acne patients, reducing the appearance

of active acne and atrophic acne scars,

which may positively impact self-esteem

and quality of life,” said Tan.

This subgroup analysis included 121

patients (mean age 22.9 years, 72.7 percent women) with moderate-to-severe

acne (IGA* 3–4) and atrophic acne scars

(>2 mm) treated with trifarotene 50 μg/g

or a vehicle cream. A third of the participants had Fitzpatrick skin phototype II.

[EADV 2024, abstract 1096]

Across age quartiles, the improvement in atrophic acne scar counts with

trifarotene always exceeded the vehicle,

with the greatest reduction in the oldest

quartile (>27 years; least squares mean

[LSM] 8 vs 2.8; p=0.0005). The corresponding LSM values in the youngest quartile (≤18 years) were 4.6 vs 1.4

(p=0.0286). Similar patterns were

seen among those aged >18–22

(LSM, 5.9 vs 3.3; p=0.0007) and

>22–27 years (LSM, 5.6 vs 3.4;

p=0.0348).

It was the same with Fitzpatrick skin

phototype, said Tan, as all subgroups

had greater improvements in atrophic

acne scar counts with trifarotene vs the

vehicle cream. However, the diff erences were only signifi cant in phototypes

II–IV (LSM, 5.5 vs 3.2; p=0.0103 [II],

5.9 vs 1.5; p=0.0006 [III], and 6 vs 3.2;

p=0.0390 [IV]). “[Nonetheless,] one of

the questions we get is whether trifarotene works as well in darker phototypes.

Here, we see that it does,” he noted.

There were also signifi cant improvements in atrophic acne scar counts with

trifarotene vs the vehicle cream across

baseline SGA* (LSM, 4.3 vs 3; p=0.0275

[SGA 2] and 7.2 vs 3.1; p=0.0002 [SGA

3]) and IGA subgroups (LSM, 5.6 vs 2.8;

p<0.0001 [IGA 3]). The greatest improvements were seen in the ‘severe’ subsets

(LSM, 9.5 vs 0.3; p<0.001 [SGA 4] and

8.7 vs 2.3; p=0.0004 [IGA 4]).

The improvements in atrophic acne

scarring with trifarotene vs vehicle were

similar in females (–5.9 vs –2.9) and

males (–6 vs 2.4; p<0.006 for both).

Individuals classifi ed as ‘White’ or

‘Asian’ had greater improvements in

atrophic acne scarring with trifarotene vs

the vehicle (–5.8 vs –2.7; p<0.001 and

–8 vs –2.3; p=0.0501).

Trifarotene was also favoured among

those categorized as ‘Black,’ but the between-group diff erence was not signifi -

cant (–5.5 vs –4.1; p=0.5142). However,

Tan noted that given the “very few Black

patients, this may be a

sample size issue rather than

a true effi cacy

issue.”

Takeaways

“It is important for us to continue

developing treatments for patients with

acne scarring because they are so bothered by it after their acne has subsided,”

Tan stressed.

“Trifarotene is one of the newer options available. It is eff ective across age

ranges, genders, and severities at baseline in terms of acne and scar global

severities. Hopefully, this [provides clinicians with] an additional option to help

patients as they come off therapy,” he

continued.

He added that should scar treatments fall short in delivering improvements, the next goal would be to determine “how we can move on to repair

procedures such as microneedling and

laser treatments. It is important for clinicians to know that [these are] readied by

topical retinoids because they increase

fi broblast activity [and enhance] procollagen and collagen [synthesis].”

*IGA/SGA: Investigator’s Global Assessment/Scar

Global Assessment

Post hoc analysis bolsters

trifarotene role in acne scar

management

(p=0.0286). Similar patterns were

seen among those aged >18–22

(LSM, 5.9 vs 3.3; p=0.0007) and

>22–27 years (LSM, 5.6 vs 3.4;

It was the same with Fitzpatrick skin

phototype, said Tan, as all subgroups

had greater improvements in atrophic

acne scar counts with trifarotene vs the

vehicle cream. However, the diff erences were only signifi cant in phototypes

II–IV (LSM, 5.5 vs 3.2; p=0.0103 [II],

5.9 vs 1.5; p=0.0006 [III], and 6 vs 3.2;

p=0.0390 [IV]). “[Nonetheless,] one of

the questions we get is whether trifarotene works as well in darker phototypes.

Here, we see that it does,” he noted.

There were also signifi cant improvements in atrophic acne scar counts with

trifarotene vs the vehicle cream across

baseline SGA* (LSM, 4.3 vs 3; p=0.0275

patients, this may be a

sample size issue rather than

a true effi cacy

issue.”

Takeaways

“It is important for us to continue

developing treatments for patients with

acne scarring because they are so bothered by it after their acne has subsided,”

Tan stressed.

As-needed ruxolitinib in children with AD:

Disease control stable through 52 weeks

ELAINE SOLIVEN

As-needed application of ruxolitinib

cream, a topically administered

selective Janus kinase 1/2 inhibitor, resulted in long-term safety and disease control in children aged 2–11 years

with mild-to-moderate atopic dermatitis

(AD), according to updated results of the

phase III TRuE-AD3 trial presented at

EADV 2024.

“Both strengths of ruxolitinib cream

were well tolerated throughout the entire

52-week study period, with no meaningful diff erences between strengths,”

said Dr Amy Paller from the University

of California San Diego in La Jolla, California, US.

In the long-term safety (LTS) period

(treat as needed: weeks 8–52), 288 children (mean age 7 years, 52.8 percent female) with moderate-to-severe AD were

evaluated. Patients who were originally

randomized to ruxolitinib cream 0.75%

(n=119) or 1.5% (n=114) continued on

their regimen, whereas those receiving

the vehicle cream were rerandomized

1:1 to ruxolitinib cream 0.75% (n=25) or

1.5% (n=24) twice daily as-needed for

recurrences of lesions for a maximum of

3 days until clearance. [EADV 2024, abstract 8082]

Safety

During the LTS period, there was a

low incidence of treatment-related treatment-emergent adverse events (TEAEs;

6.0 percent), with only 1.1 percent of application site reactions reported.

The most common TEAEs were upper respiratory tract infection (13.4 percent

[0.75%] and 16.2 percent [1.5%]), nasopharyngitis (5.2 percent and 13.1 percent, respectively), and COVID-19

(9 percent and 6.9 percent).

No cases of folliculitis or herpes zoster were observed and so were MACE,

malignancies, or thromboses.

Disease control

A higher percentage of ruxolitinib recipients achieved an Investigator’s Global Assessment score of 0 (clear) or 1

(almost clear) than the vehicle recipients

(50 percent [0.75%] and 72.4 percent

[1.5%] vs 24.5 percent) at week 8, which

further improved with as-needed ruxolitinib cream through week 52 (79.5 percent [0.75%] and 72.3 percent [1.5%]).

“Both strengths of

ruxolitinib cream were

well tolerated throughout

the entire 52-week

study period, with no

meaningful diff erences

between strengths”

Among children who switched from

the vehicle to as-needed ruxolitinib

cream, 78.9 percent (0.75%) and 72.2

percent (1.5%) achieved clear or almost

clear skin, respectively, at week 52.

Of note, “patients spent nearly half

of the LTS period off treatment due to

lesion clearance,” said Paller.

Moreover, both cohorts demonstrated a low mean aff ected body surface area during the 44-week as-needed treatment period, with 1.5 percent

(0.75%) and 1.6 percent (1.5%) in the

vehicle-ruxolitinib cohort and 2 percent

and 1.9 percent, respectively, in the

continuous ruxolitinib cohort.

“Overall, in patients aged 2–11

years with mild-to-moderate AD,

ruxolitinib cream for up to 1 year

was well tolerated … with eff ective

long-term disease control from as

early as 2 weeks,” said Paller.

“Safety and effi cacy results in children aged 2–11 years were similar to

phase III results in adolescents and

adults and maximum-use studies in children, adolescents, and adults,” she

added.

“Overall, in patients

aged 2–11 years with

mild-to-moderate

AD, ruxolitinib cream

for up to 1 year was

well tolerated … with

eff ective long-term

disease control from as

early as 2 weeks”

DOCTOR | NOVEMBER ISSUE

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

23

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

DOCTOR | NOVEMBER ISSUE

36

JAIRIA DELA CRUZ

The interleukin-17 (IL-17) blocker bimekizumab delivers sustained clinical benefi ts lasting up to 2 years for

patients with moderate-to-severe hidradenitis suppurativa (HS), as reported in a

late-breaking presentation at EADV 2024.

Two-year bimekizumab data from

the phase III BE HEARD I/II trials and the

open-label BE HEARD EXT extension

study showed that the clinically meaningful improvements in effi cacy endpoints at

1 year (week 48) were maintained over 2

years (week 96), according to lead investigator Dr Christos Zouboulis, president

of the European Hidradenitis Suppurativa

Foundation (EHSF) e.V. in Dessau, Germany.

The proportion of patients who

achieved a 50-percent improvement in

baseline lesions (HS Clinical Response

50 [HiSCR50]) slightly increased from

79.9 percent at week 48 to 85.4 percent at week 96. A similar pattern of increase was seen for the more stringent

endpoints of 75-percent improvement

(HiSCR75: from 64.0 percent to 77.1

percent), 90-percent improvement (HiSCR90: from 42.3 percent to 57.6 percent), and 100-percent improvement

(HiSCR100: from 30.2 percent to 44.2

percent). [EADV 2024, abstract 7925]

A step-down in disease

severity

The mean International Hidradenitis

Suppurativa Severity Scoring System

(IHS4) score dropped from 35.6 at baseline to 7.2 at week 98, for a mean percentage change of –79.8 percent. This

represents a signifi cant decrease in disease severity, moving patients from the

severe range (total score of 11 or higher) to the moderate range (total score of

4–10), Zouboulis pointed out.

Hidradenitis suppurativa patients get durable

benefi t with bimekizumab

He described the IHS4 data as a

landmark achievement, noting that until

now, surgical interventions were the primary means of achieving a step-down in

disease severity. “Now we have a drug

that can dial back the severity of HS. It’s

very promising.”

Additionally, the draining tunnel count

decreased by 73.7 percent at week 96,

from a mean of 3.8 at baseline to 1.1.

When multiplied by 4.4, the reduction

in draining tunnel count translates to an

estimated IHS4 score that demonstrates

a step-down in the range of HS severity

over 2 years, Zouboulis explained. [Br J

Dermatol 2017;177:1401-1409]

Improved quality of life

The mean Dermatology Life Quality

Index (DLQI) score decreased from 11.0

at baseline to 4.7 at week 96, with 33.9

percent of patients achieving a DLQI

score of 0/1.

Zouboulis emphasized that unlike

previous studies with adalimumab, where

patients often reported needing a year to

feel the full benefi ts, with bimekizumab,

patients began noticing improvements

within the fi rst 8 weeks of treatment, with

a substantial number achieving a DLQI

score of 0/1, which essentially indicates

the absence of disease for patients.

No new safety events

“No new safety signals were observed with bimekizumab, and the safety

profi le over 2 years was consistent with

fi ndings from BE HEARD I/II and studies of bimekizumab in other indications,”

Zouboulis said.

At week 96, the exposure adjusted

incidence rates per 100 person-years

were 248.9 for any treatment- emergent

adverse events (TEAEs), 7.2 for serious

TEAEs, 7.7 for severe TEAEs, and 6.3 for

TEAEs leading to treatment discontinuation. The most common TEAEs were

hidradenitis, coronavirus infection, and

mild-to-moderate oral candidiasis. Two

patients died, one due to congestive

heart failure and another due to possible

central nervous system infection in the

context of deteriorating HS.

Taken together, “these data highlight

the durability and consistency of bimekizumab treatment in patients with moderate-to-severe HS,” Zouboulis said.

“HS is such a very diffi cult disease,

and it’s gratifying to witness the emergence of a new treatment that delivers

satisfactory results for the patients,” he

added.

BE HEARD population

The current analysis included 556

patients (mean age 36.3 years, 53.8 percent female, 80.6 percent White, mean

BMI 32.5 kg/m2

) who completed 48

weeks of bimekizumab treatment in BE

HEARD I/II and entered the BE HEARD

EXT. Of these, 446 patients completed

the open-label extension phase.

In BE HEARD I/II, patients were randomly assigned to receive one of following treatments: (1) subcutaneous bimekizumab 320 mg every 2 weeks; (2)

bimekizumab 320 mg every 2 weeks to

week 16, then every 4 weeks through

week 48; (3) bimekizumab 320 mg every

4 weeks; (4) placebo to week 16, then

bimekizumab 320 mg every 2 weeks

through week 48.

In BE HEARD EXT, patients who

achieved HiSCR90 response or higher at

week 48 received bimekizumab 320 mg

every 4 weeks through week 96, while

those who had a response lower than

HiSCR90 received bimekizumab 320 mg

every 2 weeks.

24

DOCTOR | NOVEMBER ISSUE

25

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Topical delgocitinib holds the lead over oral

systemic Tx in head-to-head hand eczema trial

AUDREY ABELLA

I

n the phase III head-to-head DELTA

FORCE trial, topical delgocitinib cream

gains the upper hand over oral alitretinoin – the only oral systemic therapy

approved for the treatment of severe

chronic hand eczema (CHE) in adults

with inadequate response to topical corticosteroids.

“Topical delgocitinib cream 20 mg/g

demonstrated superior clinical treatment

eff ects and quality-of-life (QoL) improvements, and a more favourable safety profi le compared with oral alitretinoin over

24 weeks across the primary and all secondary endpoints in patients with severe

CHE,” said Dr Ana Maria Giménez-Arnau

from the Universitat Pompeu Fabra, Barcelona, Spain, at EADV 2024.

The primary endpoint was met, with

delgocitinib cream rendering a signifi -

cantly greater least squares mean (LSM)

drop in HECSI* score from baseline

to week 12 compared with alitretinoin

(–67.6 vs –51.5; p<0.001). [EADV 2024,

abstract 7986]

Delgocitinib also bested alitretinoin across key secondary endpoints,

as refl ected by the greater fraction

of participants achieving HECSI-90*

(38.6 percent vs 26 percent; p=0.003)

and IGA-CHE TS** (27.2 percent vs

16.6 percent; p=0.004) and the greater LSM drops in HESD*** itch (–3 vs

–2.4; p=0.005) and pain (–2.9 vs –2.3;

p=0.018) at week 12.

The topical cream also trumped the

oral alternative in terms of the LSM area

under the curve for HECSI-90 (49.2 vs

34.9) and for change in DLQI#

(1,124.7

vs 790.7), as well as change in HECSI

score (–69.6 vs –45.1; p<0.001 for all) at

week 24.

Giménez-Arnau noted that the improvements with delgocitinib were consistent throughout the treatment period

and manifested as early as week 1.

There were fewer treatment-emergent adverse events (AE) with the topical

vs the oral treatment option (49.4 percent vs 76.1 percent), as well as serious

AEs (2 percent vs 4.9 percent) and AEs

leading to permanent drug discontinuation (1.2 percent vs 10.1 percent).

No approved topical

treatment yet

CHE is a fl uctuating disorder characterized by itch, pain, and bothersome

signs such as erythema, scaling, hyperkeratosis, vesicles, oedema, and fi ssures

on the hands and wrists. [Contact Dermatitis 2022;86:357-378] As a result,

these manifestations lead to psychological and functional burdens that negatively impact patients’ QoL. [Adv Ther

2020;37:692-706; Contact Dermatitis

2014;70:158-168; Acta Derm Venereol

2022;102:adv00626]

“Current treatments for CHE are often unsatisfactory, and there are no topical treatments specifi cally developed

and approved for CHE,” Giménez-Arnau

said.

Delgocitinib cream – an investigational topical pan-Janus kinase inhibitor

– has shown signifi cant improvement in

all key effi cacy endpoints and was well

tolerated in the phase III DELTA 1, 2, and

3 trials, she noted.

In DELTA FORCE, 513 participants

(median age 45 years, 65 percent women) with severe CHE were randomized

1:1 to topical delgocitinib cream 20 mg/g

BID for 16 weeks or oral alitretinoin 30

mg QD for 12 weeks (as per label; could

be reduced to 10 mg). Participants may

continue treatment until week 24 should

they relapse or do not achieve suffi cient

benefi t with their respective regimens

during the initially proposed treatment

time.

The median duration of CHE was

4 years. The median HECSI and DLQI

scores were 80 and 12, respectively,

while the median HESD itch/pain scores

were 6.2/6.

“Our data support the benefi ts of

delgocitinib cream 20 mg/g as an effi -

cacious and well-tolerated topical treatment in this patient population with a

high disease burden and unmet treatment needs,” said Giménez-Arnau.

A new topical option?

“The completion of the DELTA

FORCE study marks a signifi cant milestone in our understanding of moderate-to-severe CHE treatment,” said

LEO Pharma Chief Development Offi cer

Kreesten Meldgaard Madsen, in a news

release. “With the full results now available, we have gained a new understanding of how topical treatment with delgocitinib cream compares with alitretinoin.”

“[These] data not only enhance our

knowledge of CHE management but also

potentially pave the way for a new topical option in clinicians’ therapeutic arsenal,” added LEO Pharma Head of Global

Medical Aff airs Alexander Egeberg.

*HECSI: Hand Eczema Severity Index; HECSI-90:

≥90-percent improvement in HECSI

**IGA-CHE TS: Investigator’s Global Assessment for

CHE Treatment Success, defi ned as IGA-CHE score

of 0/1 (clear/almost clear)

***HESD: Hand Eczema Symptom eDiary

#

DLQI: Dermatology Life Quality Index score

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Risankizumab eases symptoms of nonpustular

palmoplantar psoriasis

Finally, observed cases were used

to summarize the 52-week effi cacy of

risankizumab for continuous pain endpoints.

Overall, 174 patients with nPPP were

enrolled and randomized to receive either risankizumab (n=87, mean age 56.9

years, 46 percent female) or placebo

(n=87, 53.9 years, 51.7 percent female).

The mean PSS was 10.5 in the risankizumab arm and 8.9 in the placebo arm,

while the mean PGA-SP was 6.8 and

5.3, respectively. [EADV 2004, abstract

4722]

Better than placebo

In patients with baseline PGA-SP

≥4, the change from baseline in PGA-SP

at week 16 was ?3.3 with risankizumab and ?0.9 with placebo, and at week

52 was ?4.9 for patients who stayed on

risankizumab and ?4.8 for those who

switched to risankizumab from placebo.

The percent change from baseline was

?40.9 percent and ?9.7 percent at week

16 and ?62.3 percent and 69.9 percent

at week 52, respectively.

At week 16, the proportion of patients who achieved MCID of pain in

the palms of hands or soles of feet was

67.2 percent with risankizumab relative

to 45.1 percent with placebo. At week

52, this proportion was 70.3 percent

for patients who maintained the use of

risankizumab and 88.9 percent for those

who switched to risankizumab.

PSS 0/1 at week 16 was achieved by

52.1 percent (risankizumab) vs 40.5 percent (placebo) for pain, 49.3 percent vs

25.7 percent for redness, 42.5 percent

vs 25.7 percent for itching, and 56.2

percent vs 44.6 percent for burning, respectively.

By week 12, the proportion of patients achieving PSS 0/1 increased to

64.4 percent and 75.4 percent for pain,

61.6 percent and 69.6 percent for redness, 56.2 percent and 68.1 percent for

itching, and 65.8 percent and 71 percent

for burning among patients who stayed

on risankizumab therapy and those who

switched from placebo, respectively.

“Risankizumab is an approved, interleukin-23 inhibitor targeting the p19

subunit with high affi nity and specifi city,

for the treatment of moderate-to-severe psoriasis, psoriatic arthritis, and

Crohn’s disease,” according to

Lebwohl.

DOCTOR | NOVEMBER

38

STEPHEN PADILLA

I

n patients with nonpustular palmoplantar psoriasis (nPPP), treatment

with risankizumab relieves disease

symptoms, such as skin pain in palms

or soles of feet, by week 16, in a post

hoc analysis of the phase IIIb IMMprint

study. These improvements persist up

to week 52.

A chronic immune-mediated disease, nPPP “manifests as localized

plaques on palms and soles, accompanied by pain that negatively impacts

the quality of life,” said lead author Dr

Mark Lebwohl from the Icahn School of

Medicine at Mount Sinai, New York, US.

Lebwohl and his team conducted

this phase IIIb multicentre, randomized,

double-blind, placebo-controlled study

to assess the safety and effi cacy of risankizumab vs placebo in nPPP patients.

In this post hoc analysis, the research team compared item level results on the Patient Global Assessment

of Skin Pain (PGA-SP; measures of

skin pain on the palms of hands and

soles of feet) and Psoriasis Symptom

Scale (PSS; measures of pain, itching,

redness, and burning) between risankizumab and placebo at 16 weeks and

improvements through week 52.

Lebwohl and colleagues then evaluated treatment outcomes, including change from baseline

and achievement of Minimum

Clinically Important Diff erence

(MCID) of PGA-S in patients with

baseline PGA SP ≥4, as well as the

achievement of PSS by individual

symptom of 0/1 (PSS 0/1; none/

mild for pain, redness, itch, and

burning).

NOVEMBER ISSUE

26

DOCTOR | NOVEMBER ISSUE

27

CONFERENCE COVERAGE

European Academy of Dermatology and Venereology (EADV) Congress 2024 ? September 25-28

Data support abrocitinib use beyond 2 years

in adolescents with AD

MIKE NG

Treating adolescents with moderate-to-severe atopic dermatitis (AD)

with the Janus kinase 1-selective

inhibitor abrocitinib has demonstrated an

acceptable long-term safety profi le and

maintained effi cacy for up to 112 weeks,

as shown in an adolescent-focused post

hoc analysis of fi ve phase III trials.

As for treatment-emergent adverse

events (TEAEs) of special interest, no

deaths or adjudicated events of malignancies were reported. There were

incidents of serious infections and herpes zoster (HZ) infections. However, few

adjudicated opportunistic HZ infections

were noted (three patients on abrocitinib

200 mg and one on 100 mg).

The risk of thrombotic vascular events

was also monitored as TEAEs of special

interest, with a single pulmonary embolism (PE) event occurring in an adolescent

receiving abrocitinib 200 mg who had a

family history of PE and one nonserious

major adverse cardiovascular event in an

adolescent receiving the 100-mg dose.

[EADV 2024, abstract 2323]

“This analysis of adolescents with

moderate-to-severe AD treated for up to

4.6 years supports the acceptable longterm safety profi le of abrocitinib, with no

new safety signals observed,” said Professor Amy Paller, a paediatric dermatologist

at the Northwestern University Feinberg

School of Medicine in Chicago, Illinois, US.

The effi cacy of both doses of abrocitinib, measured by response rates of

75 percent or 100 percent improvement

on the Eczema Area and Severity Index

(EASI-75/-100), an Investigator’s Global

Assessment (IGA) score of 0 or 1 with a

≥2-point improvement, among other metrics, was maintained for >2 years.

Safety results: median

exposure of 2.4 years

Patients aged 12 to <18 years who

received ≥1 dose of abrocitinib while participating in JADE MONO-1, MONO-2,

TEEN, REGIMEN, and/or their extension,

JADE EXTEND, were pooled in this integrated analysis. [Lancet 2020;396:255-

266; JAMA Dermatol 2020;156:863-873;

JAMA Dermatol 2021;157:1165-1173;

J Am Acad Dermatol 2022;86:104-

112; J Eur Acad Dermatol Venereol

2023;37:2056-2066] Only those who

maintained the same abrocitinib dose

throughout the entire exposure period

were included in the safety analysis.

The median duration of abrocitinib

exposure was 882 days for the 200-mg

dose (n=289) and 863 days for the 100-

mg dose (n=201).

Serious TEAEs were reported at a

numerically higher incidence rate (IR)

with the 200-mg dose vs the 100-mg

dose (5.47 vs 3.45 patients with events

per 100 patient-years [PY]), as were TEAEs leading to abrocitinib discontinuation

(6.78 vs 5.39 per 100 PY). However, the

IRs of severe TEAEs were similar (4.67 vs

4.98 per 100 PY).

The only TEAE of special interest with

an IR >1 for both doses was “all HZ infections” (2.17 vs 1.47 per 100 PY).

“So far, we haven’t seen any of the

longer-term side eff ects we’re concerned

about. However, there are some AEs we

need to be on the lookout for, particularly

HZ,” concluded Paller.

Effi cacy results: median

exposure of ≥2.5 years

Only adolescents who were randomly

assigned to abrocitinib and subsequently

enrolled in JADE EXTEND were included

in the effi cacy analysis. The median duration of exposure was 971 days for abrocitinib 200 mg (n=170) and 899 days for

the 100-mg dose (n=187).

At 112 weeks, the EASI-75 response

rates for abrocitinib 200 mg and 100 mg

were 84.8 percent and 83.3 percent, respectively, with the corresponding IGA

0/1 rates of 57.1 percent for both.

Notably, the proportion of adolescents

achieving the more stringent EASI-100

response at 112 weeks was numerically

higher with the higher dose of abrocitinib

(30.3 percent vs 18.9 percent).

HFSA 2024

September 27-30

Cardiac biomarker profi le in ATTR-CM

looks good with vutrisiran

28

DOCTOR | NOVEMBER ISSUE

ing stabilizer therapy with tafamidis at

baseline (monotherapy population).

Maurer pointed out that the changes

in cardiac biomarkers in the monotherapy population and in the subgroup of

patients who were receiving tafamidis at

baseline further demonstrated the benefi cial eff ect of vutrisiran.

“The relative reduction with vutrisiran

vs placebo was 43 percent for NT-proBNP [p<0.000001] and 45 percent for

troponin I [p<0.000001] in the monotherapy population at month 30. On top of

tafamidis, the relative reduction with the

siRNA vs placebo was 18 percent and

10 percent for NT-proBNP [p=0.0045]

and troponin I [p=0.0849], respectively,”

he said.

Long-term stability

“Vutrisiran maintained the long-term

stability of NT-proBNP and troponin I,”

Maurer noted, adding that the median

change from baseline to month 30 in

both biomarkers was minimal and “not

really clinically relevant” compared with

the larger increases seen with placebo

across the overall population, monotherapy population, and the baseline tafamidis subgroup.

Maurer emphasized that elevated

baseline levels of NT-proBNP and troponin I were predictive of adverse clinical

events, and the favourable eff ects of vutrisiran on these biomarkers aligned with its

positive eff ects on cardiovascular events

and all-cause mortality, which were reported in the main results of HELIOS-B.

JAIRIA DELA CRUZ

I

n the treatment of patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), the use of the small

interfering ribonucleic acid (siRNA) vutrisiran helps reduce and maintain the

stability of NT-proBNP and troponin I —

biomarkers associated with increased

mortality in this population, as reported

in a late-breaking clinical research presentation at HFSA 2024.

Exploratory analyses of biomarker

data from the phase III HELIOS-B trial

showed that at month 30, vutrisiran

yielded a 32-percent relative reduction in

NT-proBNP (geometric mean fold-change

ratio, 0.68, 95 percent confi dence interval [CI], 0.61–0.76; p<0.000001) and in

troponin I (geometric mean fold-change

ratio, 0.68, 95 percent CI, 0.62–0.75;

p<0.00001) compared with placebo.

[Maurer M, et al, HFSA 2024]

The favourable treatment eff ect of

vutrisiran on cardiac biomarkers was observed as early as 6 months (NT-proBNP: p=0.0127; troponin I: p=0.0098),

with a progressive improvement over

time, noted fi rst study author Dr Mathew

Maurer from Columbia University Irving

Medical Center, New York, New York,

US.

Additionally, vutrisiran consistently

improved cardiac biomarkers across various subgroups, as defi ned by age, ATTR

type, NYHA class, and baseline NT-proBNP levels, both in the overall population

and in the cohort of patients not receiv-

[N Engl J Med 2024;doi:10.1056/NEJMoa2409134]

HELIOS-B showed that “vutrisiran

rapidly knocked down TTR, lowered the

risk of all-cause mortality and cardiovascular events compared with placebo,

and preserved functional capacity and

quality of life in a contemporary population with ATTR-CM, including [individuals with] substantial use of background

therapy,” he continued. [N Engl J Med

2024;doi:10.1056/NEJMoa2409134]

The siRNA had “acceptable safety

and tolerability profi le, as previously established,” Maurer said.

A total of 665 patients with ATTR-CM

participated in HELIOS-B. At baseline,

approximately 40 percent of patients

were receiving tafamidis, 3 percent were

receiving SGLT2 inhibitors, and 80 percent had substantial use of diuretics. The

patients were randomly assigned to receive vutrisiran 25 mg or placebo subcutaneously every 12 weeks for up to 36

months.

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

29

CONFERENCE COVERAGE

ELVIRA MANZANO

Semaglutide improves exercise

function in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) in a

secondary analysis of the prespecifi ed

pooled STEP-HFpEF and STEP-HFpEF

DM trials presented at HFSA 2024.

“The greatest improvements were

observed in patients with the most

weight loss at 52 weeks,” reported study

author Dr Mikhail Kosiborod, a cardiologist at Saint Luke’s Mid-America Heart

Institute and professor of medicine at

the University of Missouri-Kansas City

School of Medicine, Missouri, US.

“HFpEF represents the majority of

HF cases in the community, and among

those with the condition, the majority are

also living with overweight or obesity,”

he said. “Previous studies have shown

that patients with obesity-related HFpEF

experience worse burden of symptoms,

physical limitations, and a greater degree

of exercise impairment.”

Semaglutide impact

on 6MWD

Kosiborod and colleagues sought to

evaluate the effi cacy of semaglutide 2.4

mg once weekly in relation to improving patients’ 6-minute walking distance

(6MWD). “Specifi cally, we wanted to

know the change in 6MWD according to

the magnitude of weight loss.”

The pooled trials included 1,145

adult patients with HFpEF and a BMI of

≥30 kg/m2

with (STEP-HFpEF DM) or

without diabetes (STEP-HFpEF).

Participants were randomly assigned

to semaglutide 2.4 mg once weekly or

placebo. The dual primary endpoints

were changes in the Kansas City CardioEvidence supports semaglutide

for obesity-related HFpEF

myopathy Questionnaire (KCCQ) score

and body weight from baseline to 52

weeks. The main fi ndings reported previously showed that semaglutide 2.4 mg

improved HF-related symptoms and

physical limitations and reduced

body weight vs placebo. [Lancet

2024;403:1635-1648]

In the current subanalysis,

researchers evaluated semaglutide 2.4 mg for 20- and

52-week changes in 6MWD

across subgroups based on

weight loss and the impact of baseline

walk distance on the primary and key

secondary endpoints.

Participants were grouped into one

of three tertiles of increasing 6MWD at

baseline. The lowest tertile on 6MWD

at baseline was older with higher waist

circumference, BMI, C-reactive protein

and N-terminal pro-B-type natriuretic

peptide levels. This group had a higher

NYHA class and lower KCCQ score. The

left ventricular ejection fraction was not

signifi cantly diff erent between tertiles of

baseline walk distance.

“Early improvement in 6MWD was

observed in patients assigned to semaglutide 2.4 mg vs placebo at 20 weeks

[diff erence of 14.6 m] and was sustained

out to 52 weeks [diff erence of 17.1 m;

p<0.0001 for both],” Kosiborod said.

“Improvement in walk distance was consistent across all subgroups.”

The diff erence in 6MWD increased

further in patients with proportionately larger decreases in body weight with

semaglutide from baseline to week 52

(0.1 m for <5 percent decrease, 17.1 m

for a 5–10 percent decrease, 22.2 m for

a 10–15 percent decrease, 24.3 m for a

15–20 percent decrease, and 34.7 m for

≥20 percent decrease).

The hierarchical composite endpoint

and C-reactive protein ratio were also

consistent across all tertiles of baseline

6MWD, with fewer serious and cardiac

adverse events.

Multiple benefi ts

for patients

“In patients with obesity-related HFpEF, baseline impairment in exercise

function was associated with greater

infl ammation, congestion and adiposity,” said Kosiborod. “In this secondary

analysis, semaglutide improved 6MWD

as early as 20 weeks, preceding maximal

weight loss, with a sustained eff ect at 52

weeks.”

This was in addition to improving

HF-related symptoms, physical limitations and exercise function. Reductions

in infl ammation, congestion, and body

weight were all consistent regardless of

baseline exercise function, he added.

Evidence supports semaglutide

for obesity-related HFpEF

myopathy Questionnaire (KCCQ) score

and body weight from baseline to 52

weeks. The main fi ndings reported previously showed that semaglutide 2.4 mg

improved HF-related symptoms and

physical limitations and reduced

body weight vs placebo. [Lancet

In the current subanalysis,

researchers evaluated semaglutide 2.4 mg for 20- and

“Semaglutide improved

6MWD as early as

20 weeks, preceding

maximal weight loss,

with a sustained eff ect

at 52 weeks”

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

CONFERENCE COVERAGE

Novel HU6 reduces weight without muscle loss

in patients with obesity-related HFpEF

bo for 19 weeks. Majority of the participants

were female with a mean BMI of 39 kg/m2

and a peak V02

of 13.4 mL/kg/minute.

In terms of safety, the most common

adverse events (AEs) reported in the HU6

and placebo arms were diarrhoea (18.2

percent vs 6.3 percent), COVID-19 (15.2

percent vs 3.1 percent), and dyspnoea

(12.1 percent vs 0 percent).

Although more serious AEs occurred

in the HU6 group than the placebo group

(12.1 percent vs 3.1 percent), they were

all deemed unrelated to the study drug

as per the blinded investigator team, said

Pandey.

“HU6 appeared safe and well tolerated [in this patient population],” he added.

“Overall, the phase IIa HuMAIN results showing signifi cant reductions in

body fat and visceral fat in patients with

obesity-related HFpEF, who typically

have excess fat throughout their cardiovascular system and systemic infl ammation, are extremely promising given that

the study participants had obesity, were

older, and with multiple medical conditions,” Pandey said in a press release.

“We were also encouraged to see the

preservation of lean muscle mass, which

is particularly important for older patients

with HFpEF, who are often frail and have

reduced muscle mass.”

However, as the HuMAIN-HFpEF trial was considered a small study with a

short study duration, “future larger trials

with longer-term follow-up are needed to

evaluate whether HU6 can improve functional status and clinical outcomes in the

growing population of patients with obesity-related HFpEF,” he noted.

*HuMAIN-HFpEF: Hepatic Uncoupler Mitochondrial

Accelerator IN HFpEF

DOCTOR | NOVEMBER ISSUE

30

ELAINE SOLIVEN

Treatment with HU6, a novel, fi rst-inclass controlled metabolic accelerator, signifi cantly reduces body

weight while preserving lean body mass

in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), according to the HuMAIN-HFpEF*

trial presented at HFSA 2024.

From baseline to week 19, patients

treated with HU6 achieved a signifi cant

weight loss of 2.9 kg (p=0.003), with a

mean percentage change in body weight

of -2.7 percent (p=0.003), compared

with placebo. [HFSA 2024, Late Breaking Clinical Research Session II]

In terms of changes in body composition between baseline and week 19,

using the InBody Scale, HU6-treated patients had a signifi cant reduction of 6.9

percent in total body fat (p=0.0001) than

placebo-treated patients.

In particular, visceral fat decreased by

6.6 percent (p=0.001) in the HU6 arm,

but no signifi cant diff erence in lean body

mass was observed between the treatment arms (diff erence of 0.8 percent;

p=0.30).

Taken together, “the weight loss

eff ect of HU6 [also led to] favourable

changes in body composition, including

signifi cant reductions in overall fat mass

and visceral adiposity and preservation

of lean body mass,” said lead author Dr

Ambarish Pandey from the Department

of Internal Medicine, Division of Cardiology and Geriatrics at the University of

Texas Southwestern Medical Center in

Dallas, Texas, US.

In previous studies, “the GLP-1 receptor agonist semaglutide signifi cantly

reduced body weight … However, concerns have been raised about loss of

muscle mass with GLP-1 receptor agonists in older patients with HFpEF who

have sarcopenic obesity and signifi cant

skeletal muscle dysfunction,” Pandey

noted.

Based on the current fi ndings of the

HuMAIN-HFpEF study, it was demonstrated that HU6 therapy selectively

reduced body fat while simultaneously

preserving skeletal muscle mass in older

patients with obesity-related HFpEF, thus

meeting the need for novel weight loss

interventions.

This multicentre, double-blind,

dose-escalation, phase IIa HuMAIN-HFpEF trial analysed 66 patients (mean age

64 years) with obesity-related HFpEF who

were randomized in a 1:1 ratio to receive

either HU6 (150, 300, or 450 mg) or place

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

CONFERENCE COVERAGE

DOCTOR | NOVEMBER ISSUE

31

STEPHEN PADILLA

Treatment with mavacamten improves cardiac biomarkers of wall

stress and injury, as shown by reduced NT-proBNP and troponin levels,

without sustained left ventricular ejection

fraction (LVEF) reductions, according

to the preliminary fi ndings of the EMBARK-HFpEF trial.

“This is the fi rst experience with cardiac myosin inhibition in patients with

heart failure with preserved ejection fraction [HFpEF],” said lead author Dr Sanjiv Shah from Northwestern University

Feinberg School of Medicine, Chicago,

Illinois, US.

“Twenty-six-week treatment with mavacamten improved cardiac biomarkers

of wall stress (NTproBNP) and injury (troponin),” he said. In addition, “[t]here was

a good safety profi le with no sustained

LVEF reductions and no LVEF <30 percent.”

Shah and his team conducted EMBARK-HFpEF, a phase IIa, open-label,

single-arm, multicentre trial, to examine

the eff ects of myosin inhibition with mavacamten in patients with HFpEF.

Those aged ≥50 years, with LVEF

≥60 percent, and objective evidence of

HF (ie, hospitalization for HF, elevated

LV fi lling pressure, elevated historical

NT-proBNP or BNP, elevated E/e’ ratio,

or left atrial enlargement with chronic

loop diuretic use) were included in the

trial.

“At screening, elevated NT-proBNP,

LVEF ≥60 percent, and LV wall thickness

≥12 mm or elevated LV mass index were

required,” Shah said. “Key exclusions

were prior hypertrophic cardiomyopathy (HCM) or infi ltrative cardiomyopathy,

signifi cant valve disease, and prior LVEF

<45 percent.”

Eligible patients received mavacamten for 26 weeks, beginning

at a dose of 2.5 mg and titrated

up to 5 mg at week 14 based on

LVEF and NT-proBNP. The investigators did week 34 “end-ofstudy labs” 8 weeks after treatment cessation. Changes in

NT-proBNP and troponin were

the primary effi cacy endpoints,

while safety outcomes included

LVEF and adverse events.

Cardiac biomarkers

Thirty patients (mean age 75 years,

53 percent female, 10 percent Black)

met the inclusion criteria and were enrolled across 14 sites in the US and Canada. Their geometric mean NT-proBNP

was 520 pg/mL and mean LVEF was 67

percent, with high-sensitivity troponin T

(hsTnT) of 0.017 ng/mL and high-sensitivity troponin I (hsTnI) of 8.35 pg/mL.

Many patients also had comorbidities.

Use of mavacamten resulted in a

reduction in NT-proBNP by 26 percent

(95 percent confi dence interval [CI], ?44

to ?4), hsTnT by 13 percent (95 percent

CI, ?23 to ?3), and hsTnI by 20 percent

(95 percent CI, ?32 to ?6). [Shah S, et al,

HFSA 2024]

After discontinuation of mavacamten, biomarker values returned to baseline levels. NYHA class improved in 42

Mavacamten improves cardiac

biomarkers in patients with HFpEF

“These results

support further

investigation

of myosin inhibition

for HFpEF”

percent of patients and remained unchanged in the rest. Diastolic function

parameters also improved, while mean

LVEF decreased by 3.2 percent during

treatment.

Three patients (10 percent) had

treatment interruption due to LVEF <50

percent (n=2) or >20 percent relative

decrease from baseline (n=1; LVEF=58

percent). The lowest LVEF at interruption

was 40 percent. All three patients had

LVEF recovery, and one restarted and

completed treatment.

No deaths occurred during the treatment-emergent period, and one patient

had worsening HF, which was deemed

unrelated to mavacamten treatment.

“These results support further investigation of myosin inhibition for HFpEF,”

Shah said.

“The AURORA HFpEF phase II [randomized controlled trial] of a next-generation myosin cardiac inhibitor (ie,

BMS-98645/MYK-224) is currently well

underway to further validate and expand

upon the EMBARK-HFpEF fi ndings,” he

added.

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

32

CONFERENCE COVERAGE

Mitral TEER clips hold benefi ts at 1 year

in patients with atrial SMR

MIKE NG

An analysis of the EXPANDed patient-level pooled cohort presented

at HFSA 2024 demonstrates clinical benefi ts in patients with atrial secondary mitral regurgitation (SMR) at 1 year following a mitral transcatheter edge-to-edge

repair (TEER) procedure using newer-generation clip devices. These included a signifi cant reduction in MR and substantial improvements in patient-reported outcomes.

From 3.8 percent of patients with atrial

SMR having an MR grade ≤1+ per independent echocardiography core laboratory

assessment at baseline, the proportion increased to 95.2 percent 1 year after TEER.

The improvement in functional capacity, as evidenced by a shift in New

York Heart Association (NYHA) functional

classes, was also signifi cant. The proportion of patients with atrial SMR categorized into class I or II increased from

26.2 percent at baseline to 79.5 percent

at 1 year. [HFSA 2024, abstract P2424]

Quality of life, measured using the Kansas City Cardiomyopathy Questionnaire

overall summary (KCCQ-OS) scores, improved by 19 points from baseline to 1 year

after TEER (p<0.001). “This is considered

a clinically signifi cant improvement,” said

lead author Professor Mark Ricciardi, Chair

of Cardiology at the NorthShore University

HealthSystem in Evanston, Illinois, US.

“Importantly, the all-cause mortality

rate was low at 9 percent after 1 year.

This compares favourably with other patients with SMR in the EXPANDed cohort

and patients in previous clinical trials of

SMR,” stated Ricciardi.

Outcomes comparable

to ‘all SMR’ patients

The EXPANDed cohort was examined

to study the characteristics and outcomes

of patients with atrial SMR (n=160), defi ned

as SMR with a history of atrial fi brillation (AF)

and a left ventricular (LV) ejection fraction

≥45 percent, along with evidence of left

atrial (LA) enlargement based on cutoff s for

LA volume and/or diameter parameters.

On average, patients in the atrial

SMR subgroup had 1.4 clips implanted,

the same as in the overall SMR cohort

(‘all SMR’; n=967). Acute procedural

success rates were high in both patient

groups (97.5 percent vs 95.8 percent),

with no procedural deaths.

For the comparison of outcomes at

1 year, the proportions of patients in the

all SMR cohort with an MR grade of ≤1+

and in NYHA class I or II were 94.3 percent and 77.9 percent, respectively. The

improvement in KCCQ-OS scores from

baseline (19 points; p<0.001) was identical to the atrial SMR subgroup.

The magnitude of reduction in annualized HF hospitalization rates after

the procedure was similar between atrial

SMR patients and all SMR patients (56

percent vs 60 percent reduction).

All-cause mortality may represent a

slight discrepancy, as the Kaplan-Meier

1-year estimates were 9 percent for atrial

SMR patients vs 15.7 percent for all SMR

patients.

Few single-leafl et device attachment

events were reported at 1 year, with one

event occurring in the atrial SMR subgroup

(0.6 percent vs 0.5 percent in all SMR).

EXPAND and EXPAND G4

EXPANDed was established by pooling

patient-level data from two global, prospective, single-arm, post-market observational

studies, EXPAND and EXPAND G4, which

collected safety and eff ectiveness data on

third- and fourth-generation clip devices,

respectively, in the real world. [JACC Cardiovasc Interv 2023;16:589-602; JACC

Cardiovasc Interv 2023;16:2600-2610]

Atrial SMR, which has emerged as

a topic of interest, is characterized by a

dilated left atrium and mitral annulus with

preserved LV systolic function. [J Am Coll

Cardiol 2011;58:1474-1481] However,

the exact defi nition of atrial SMR is not

consistent across studies, and the presence of AF may not be a prerequisite for

an atrial SMR diagnosis. [JAMA Netw

Open 2024;7:e2428032]

The defi nition of atrial SMR in the current analysis follows a previous analysis

of EXPAND alone. [JACC Cardiovasc Interv 2022;15:1723-1730]

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

33

CONFERENCE COVERAGE

AUDREY ABELLA

The use of SGLT2 inhibitors nearly

halves the risk of all-cause mortality at 3 years in patients with

wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) and type 2 diabetes (T2D), fi ndings from an observational

study suggest.

For the primary endpoint of risk of

all-cause mortality, the Kaplan-Meier

survival curve refl ected a hazard ratio

of 0.53 (95 percent confi dence interval,

0.36–0.74; p<0.001) with SGLT2 inhibitor use in wild-type ATTR-CM patients,

as opposed to those who were not on

SGLT2 inhibitor therapy.

The risks were similar for the secondary endpoints of atrial fi brillation, endstage renal disease, ventricular tachycardia/fi brillation, and stroke at 3 years

between participants on SGLT2 inhibitor

therapy and those who were not.

High mortality

“Wild-type ATTR-CM is a progressive

restrictive cardiomyopathy characterized by deposition of misfolded transthyretin in the myocardium, resulting in

high mortality. This disease burden and

clinical trajectory is further worsened by

concomitant T2D,” noted the group of

researchers from the Division of Cardiovascular Disease at the University of Alabama at Birmingham in the US, in their

poster presented at HSFA ASM 2024.

SGLT2 inhibitors have shown benefi t

for heart failure hospitalizations in T2D

patients and have now been recommended for use across the spectrum of

left ventricular ejection fraction.

“[However,] limited data exist regarding SGLT2 inhibitor use in wild-type ATTR-CM patients,” said the researchers.

“[Hence, we conducted] a retrospective cohort study … using federated real-world electronic health record (EHR)

data assimilated from large academic

medical centres across the US.”

The researchers characterized 1,531

T2D patients as also having wild-type

ATTR-CM. Of these, 596 (38.9 percent)

were on SGLT2 inhibitors. After propensity score matching, each study group

comprised 534 participants (mean age

at index 75 years). The cohort was stratifi ed based on SGLT2 inhibitor use at the

time of diagnosis of wild-type ATTR-CM.

[Parcha, V, et al, HFSA 2024]

“Limited data exist

regarding SGLT2

inhibitor use in

wild-type ATTR-CM

patients”

Are SGLT2 inhibitors cardioprotective

for wild-type ATTR-CM patients?

About 80 percent of the overall participants had hypertension, over half had

ischaemic heart disease, and 50 percent had chronic kidney disease. Other

comorbidities were neoplasms, obesity,

chronic obstructive pulmonary disease,

depression, cerebral infarction, asthma,

and nicotine dependence. Roughly a

third of participants were on background

tafamidis.

More studies needed

to validate cardioprotective

eff ect

However, the fi ndings may have been

limited by the retrospective nature of the

study, the investigators noted. “EHRbased, real-world data utilizing standardized codes was used to defi ne study

variables and outcomes, which are subject to coding errors and cannot quantify

the severity of the outcomes.”

Moreover, residual confounding from

unmeasured variables may have contributed to the observed associations with

the outcomes despite propensity score

matching, they added.

The researchers called for prospective randomized clinical trials to further

evaluate the cardioprotective effi cacy of

SGLT2 inhibitors in wild-type ATTR-CM

patients with T2D.

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

34

CONFERENCE COVERAGE

Acoramidis boosts clinical outcomes

in ATTR-CM

ELAINE SOLIVEN

Treatment with the investigational

agent acoramidis signifi cantly reduces all-cause mortality (ACM)

and recurrent cardiovascular-related

hospitalizations (CVH) at 30 months

in patients with transthyretin amyloid

cardiomyopathy (ATTR-CM), according

to a post hoc analysis of the phase III

ATTRibute-CM trial presented at HFSA

2024.

Based on the negative binomial

regression and Andersen-Gill analyses, acoramidis signifi cantly reduced

the risk of the composite outcome of

ACM and recurrent CVH by 42 percent

(p=0.0005) and 30.5 percent (hazard

ratio [HR], 0.695; p=0.0008), respectively, at month 30 compared with

placebo. [Judge, et al, HFSA

2024]

Additionally, patients treated with

acoramidis had lower rates of ACM

(19.3 percent vs 25.7 percent) and

CVH (26.7 percent vs 42.6 percent)

than those treated with placebo, resulting in fewer patients having ACM

or CVH by month 30 in the acoramidis

arm (36 percent vs 51 percent).

Acoramidis is an investigational,

next-generation, orally administered,

high-affi nity transthyretin (TTR) stabilizer that acts to inhibit dissociation of

tetrameric TTR and leads to more than

90-percent stabilization across the

dosing interval as measured ex vivo. [N

Engl J Med 2024;390:132-142]

“This post hoc analysis

provides further evidence

that near-complete TTR

stabilization with acoramidis can improve clinical outcomes

for patients with ATTR-CM. The reduction of hospitalizations and ACM

seen in ATTRibute-CM heightens the

case for acoramidis as a fi rst-line therapy given its potential to improve the

overall quality of life for patients,” said

lead author Dr Daniel Judge from the

Medical University of South Carolina,

Charleston, South Carolina, US, in a

press release.

The study included 611 patients

(mean age 77 years) with ATTR-CM

who were randomized 2:1 to receive

either acoramidis (n=409) or placebo

(n=202). All baseline characteristics

were similar in both groups.

In terms of safety, the incidence of

serious treatment-emergent adverse

events (TEAEs) was lower in the acoramidis arm than the placebo arm (54.6

percent vs 64.9 percent). However,

more treatment-related AEs were observed with acoramidis (11.9 percent

vs 5.2 percent).

“As previously reported, no safety signals of potential clinical concern

were identifi ed in the ATTRibute-CM,”

Judge noted.

In light of the positive results of the

ATTRibute-CM trial, a new drug application has been submitted to the US

FDA. Decision is expected in 2025.

“As previously

reported, no safety

signals of potential

clinical concern

were identifi ed in the

ATTRibute-CM”

ACM and recurrent CVH by 42 percent

(p=0.0005) and 30.5 percent (hazard

ratio [HR], 0.695; p=0.0008), respectively, at month 30 compared with

placebo. [Judge, et al, HFSA

2024]

“This post hoc analysis

provides further evidence

that near-complete TTR

stabilization with acoroverall quality of life for patients,” said

lead author Dr Daniel Judge from the

Medical University of South Carolina,

Charleston, South Carolina, US, in a

press release.

The study included 611 patients

(mean age 77 years) with ATTR-CM

who were randomized 2:1 to receive

either acoramidis (n=409) or placebo

(n=202). All baseline characteristics

were similar in both groups.

In terms of safety, the incidence of

serious treatment-emergent adverse

events (TEAEs) was lower in the acoramidis arm than the placebo arm (54.6

percent vs 64.9 percent). However,

more treatment-related AEs were observed with acoramidis (11.9 percent

vs 5.2 percent).

“As previously reported, no safety signals of potential clinical concern

were identifi ed in the ATTRibute-CM,”

Judge noted.

In light of the positive results of the

ATTRibute-CM trial, a new drug application has been submitted to the US

FDA. Decision is expected in 2025.

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

35

CONFERENCE COVERAGE

Thumbs up for HeartMate 3 in cohorts

with high perioperative risk

Patients with advanced CKD

French and colleagues examined

patients with advanced CKD, defi ned

based on eGFR levels measured in the

morning of LVAD implantation. Of the patients, 157 had eGFR ≥30 mL/min/1.73

m2

(stage 4-5 CKD) and 36 had eGFR

≤29 mL/min/1.73 m2

(control).

The 30-day mortality was similar

between the stage 4-5 CKD and control groups (p=0.1), as was mortality at

1 year (p=1) and 2 years (p=0.5). [HFSA

2024, poster 4145394;214]

The length of ICU stay postimplantation was 13.5 days in the stage 4-5 CKD

group vs 10.3 days in the control group

(p=0.2), and the length of total hospitalization was 25.8 vs 23.7 days, respectively (p=0.5). Patients with advanced CKD

were readmitted 1.47 times per year,

while those in the control group were readmitted 1.92 times per year (p=0.3).

Life-saving therapy

“LVADs are a life-saving therapy for

patients with severe heart failure. The

only currently commercially available

LVAD is the HeartMate 3, which features

an intrathoracic, fully magnetically levitated, centrifugal-fl ow pump. Currently,

there is minimal evidence on the eff ectiveness of the HeartMate 3 in patients

with class III obesity and those with advanced CKD,” French noted.

He emphasized that the fi ndings

from the subgroup analyses indicate that

HeartMate 3 should be considered in all

patients with morbid obesity who have

no contraindications to LVAD implantation and that stage 4-5 CKD should not

be regarded as a contraindication to device implantation.

The study was limited by its retrospective nature, use of data from a single

medical centre, and the relatively small

sample size. French acknowledged that

while the patients included in the study

were primarily admitted or transferred to

their institution, some admissions may

have possibly occurred outside their system and were not accounted for in the

readmission data.

JAIRIA DELA CRUZ

The HeartMate 3 left ventricular

assist device (LVAD) can off er

a lifeline to patients with severe

heart failure, including those with morbid obesity and advanced chronic kidney disease (CKD), medical conditions

that carry increased perioperative risks,

as suggested in a retrospective cohort

study.

In a cohort of 193 patients who received a HeartMate 3 LVAD, “we found

no signifi cant diff erence in any measured

outcomes [following HeartMate 3 implantation] for severely obese patients

and those with stage 4 or 5 CKD when

compared with controls,” said fi rst study

author Dr Benjamin French from the Emory University School of Medicine in Atlanta, Georgia, US.

Patients with morbid

obesity

Of the patients, 27 had an average

BMI of 45.0 kg/m2

and 166 had a BMI of

<40 kg/m2

(control). Survival was similar

between the two patient groups at the

following timepoints: 30 days (p=0.3), 1

year (p=0.8), and 2 years (p=0.9). [HFSA

2024, poster 4145193;012]

The length of ICU stay after implantation was 10.1 days in the severely

obese group vs 11.6 days in the control

group (p=0.5), and the length of total

hospitalization was 22.9 vs 24.2 days,

respectively (p=0.7). Patients in the severely obese group were readmitted 1.6

times per year, while those in the control group were readmitted 1.9 times per

year (p=0.5).

Finally, the incidence of new driveline

infections at 2 years after implantation

did not signifi cantly diff er between the

two groups (p=0.14).

Heart Failure Society of America (HFSA) Annual Scientifi c Meeting 2024 ? September 27-30

DOCTOR | NOVEMBER ISSUE

36

CONFERENCE COVERAGE

Afi camten improves clinical outcomes

in obstructive HCM

STEPHEN PADILLA

Patients with obstructive hypertrophic cardiomyopathy (oHCM) can

derive broad clinical benefi ts from

treatment with afi camten, which include

complete haemodynamic response and

improved exercise capacity among others, as shown in the SEQUOIA-HCM

study.

“Over a relatively short treatment period, nearly all patients (97 percent) on

afi camten experienced a clinically meaningful improvement in one or more clinically relevant outcome measures, including complete haemodynamic response,

relief in limiting symptoms, enhanced

exercise capacity, and signifi cant decrease in NT-proBNP,” said lead author

Dr Martin S Maron from Lahey Hospital

and Medical Centre, Burlington, Massachusetts, US.

In the study, Maron and his team randomized symptomatic oHCM patients

in a 1:1 ratio to receive either afi camten

(n=142) or placebo (n=140) daily for 24

weeks.

The following outcomes were assessed at 24 weeks and compared with

baseline: (1) improvement in the burden

of limiting symptoms with ≥1 change in

NYHA class and/or ≥10-point increase in

the Kansas City Cardiomyopathy Questionnaire-Clinical Summary score (KCCQ-CCS), (2) complete haemodynamic

response (resting and Valsalva gradient

of <30 and <50 mm Hg, respectively), (3)

≥1.5 mL/kg/min change in peak oxygen

consumption (pVO2

), and (4) ≥50-percent

decrease in serum NT-proBNP levels.

In addition, the research team also

evaluated the eligibility of patients with

oHCM for septal reduction therapy (SRT).

[Maron MS, et al, HFSA 2024]

Of the patients randomly allocated to afi camten, 84 percent achieved

a ≥50-percent reduction in NT-proBNP

levels, 71 percent showed improvements

in limiting symptoms, 68 percent had a

complete haemodynamic response, and

47 percent exhibited better exercise capacity at week 24. Of note, all these improvements were markedly greater than

those seen with placebo (p≤0.002).

Moreover, 97 percent of patients who

received afi camten demonstrated improvements in one or more of the above

clinically relevant outcome measures,

which included 23 percent who had improvements in all four measures. These

rates were signifi cantly higher than those

seen in the placebo group (59 percent

and 0 percent, respectively; p<0.001 for

both comparisons).

SRT eligibility

Notably, 88 percent of patients in the

afi camten group who were initially eligible

for SRT no longer met the criteria for such

therapy at week 24. In comparison, this

rate was signifi cantly higher than the 52

percent in the placebo group (p=0.002).

“The combined eff ect of afi camten on

improving symptomatic status and haemodynamics converted most of those patients who were guideline eligible for SRT

at baseline to no longer meeting those

criteria at week 24,” Maron said.

“These fi ndings underscore the

broad clinical effi cacy of afi camten for the

treatment of patients with symptomatic

oHCM, including those eligible for SRT,”

he added.

Afi camten is a novel cardiac myosin inhibitor that reduces outfl ow gradients and

improves functional capacity in oHCM. [N

Engl J Med 2024;390:1849-1861]

In patients with oHCM, “l(fā)eft ventricular

outfl ow tract obstruction is the predominant mechanism responsible for limiting

symptoms and other adverse consequences,” according to Maron.

37

DOCTOR | NOVEMBER ISSUE

PHARMACISTS IN FOCUS

At the forefront of primary

healthcare

The WHO defi nes primary healthcare as

a “whole-of-society approach” to eff ectively

achieve the highest possible level of health

for everyone. This approach comprises

three components: comprehensive integrated health services, multisectoral policies,

and personal health empowerment. [https://

www.who.int/news-room/fact-sheets/detail/primary-health-care]

Mr Sinclair emphasized pharmacists’

versatility, noting their ability to off er various

health services within primary healthcare,

including optimizing medication and paI

n celebration of World Pharmacists Day on September 25, Kenvue brought together a panel of experts to discuss

how pharmacists are contributing in signifi cant ways to delivering eff ective, accessible healthcare and improving

patient outcomes. Mr Paul Sinclair, President of the International Pharmaceutical Federation, identifi ed the roles

pharmacists play in primary healthcare. Dr Angeline Yong, Consultant Dermatologist and Dermatological Laser

Surgeon, Angeline Yong Dermatology Clinic, Singapore, described pharmacists as trusted advisors guiding good

skincare practices. Dr Giridhar Sethuraman, Chief Consultant Neonatologist at Neolife Children’s Hospital, Chennai,

India, focused on the role of pharmacists in managing atopic dermatitis in children. Dr Edwin Heng, Periodontist at

Farrer Park Medical Centre, Singapore, discussed the critical connection between oral health and overall well-being.

Professor Mohammad Haniki from the Kulliyyah of Pharmacy, International Islamic University of Malaysia, emphasized

the importance of training pharmacists to support smoking cessation eff orts.

tient safety, managing noncommunicable

diseases, and preventing common infectious diseases. “Many of these are currently

being delivered through community pharmacies worldwide.”

He added that pharmacists can help

empower individuals and communities to

take charge of their own health by promoting equitable access to healthcare services,

advocating for antimicrobial stewardship,

improving health literacy, preventing risk

factors, and encouraging self-care.

“Interprofessional collaboration is the

way going forward for an eff ective primaI

n celebration of World Pharmacists Day on September 25, Kenvue brought together a panel of experts to discuss

how pharmacists are contributing in signifi cant ways to delivering eff ective, accessible healthcare and improving

Beyond medication dispensing:

The expanding role of pharmacists in healthcare

Mr Paul Sinclair

ry healthcare model,” he said,” adding that

pharmacists must be fairly compensated

for their contributions to primary healthcare.

Dr Angeline Yong

“Skin collagen is essential for maintaining skin health,” Dr Yong said. “Collagen

loss, due to intrinsic and extrinsic factors,

leads to wrinkles and visible signs of ageing.”

She put emphasis on retinoids, vitamin

C, and growth factors as critical ingredients

that can help boost collagen production.

According to Dr Yong, pharmacists are

uniquely positioned to educate patients

about best practices in skin care. “These

include using sun protection and incorporating key ingredients into their daily routine

based on their specifi c needs, whether for

sensitive skin or anti-ageing purposes.”

Drugstores off er a platform for pharmacists to engage directly with consumers, and

each of these encounters is an opportunity

to recommend safe and eff ective options,

ensuring products are not just trendy but

genuinely benefi cial, Dr Yong pointed out.

“This is especially crucial in today’s era of

social media, which is saturated with confl icting skincare information,” she added.

“Pharmacists are more than just dispensers of medication. They are valuable

partners in skin care, off ering education,

guidance, and support to patients seeking to improve their skin health,” Dr Yong

emphasized.

Trusted advisors in skincare

Collagen-boosting

skincare ingredients

Retinoids

These vitamin A derivatives are

known for their ability to boost

collagen production, reduce fi ne lines,

and improve skin texture. [J Drugs

Dermatol 2022;21:s4-s10; J Cosmet

Dermatol 2016;15:49-57]

Vitamin C

A potent antioxidant that can

help brighten the skin, reduce

hyperpigmentation, and enhance

collagen synthesis. [J Cosmet

Dermatol 2022;21:2349-2359]

Growth factors

These signalling molecules can

stimulate collagen production and

improve skin elasticity. [Dermatol Ther

2023;13:169-186]

38

DOCTOR | NOVEMBER ISSUE

PHARMACISTS IN FOCUS

Dr Giridhar Sethuraman

Partners in paediatric AD

management

Atopic dermatitis (AD), a chronic skin

condition prevalent in infants and young

children, is characterized by impaired

skin barrier function. [Indian J Pediatr

2014;81:381-390; Dermatol Res Pract

2012:2012:198789] When the skin barrier is compromised, irritants and allergens enter the skin, causing infl ammation.

[Nat Genet 2006;38:399-400] Infl ammation triggers itching, causing the patient

to scratch, and creating a vicious cycle

called the “itch-scratch-itch” cycle, said Dr

Sethuraman.

“The key principle in AD management

is to ensure that the skin barrier is not

disrupted and, in case of disruptions, to

allow repair,” he pointed out. He added

that emollients can help maintain the skin

barrier, increasing and locking in moisture,

and reducing infl ammation.

Partners in paediatric AD

management

Disrupted skin barrier

leads to atopic-prone skin

Pharmacists can help physicians select the right emollients for preventing

and managing AD fl ares in children. “This

will go a long way in reducing the disease

burden and improving the quality of life of

these children … it will also ensure treatment adherence because they’re happy

with the results,” said Dr Sethuraman.

He added that pharmacists can use

their knowledge of AD and emollient ingredients to educate and counsel patients

on the proper use of those emollients,

help identify early signs of fl are-ups, and,

if warranted, refer patients to paediatricians.

Allies in smoking cessation

“Given the global and regional prevalence and burden of tobacco use, particularly as a risk factor for noncommunicable

diseases, the pharmacists’ role in this area

must be expanded and consolidated,” Prof

Haniki pointed out.

Studies on pharmacist-led smoking

cessation programmes conducted largely

in Malaysia have shown that counselling

alone, even when delivered in under 3 mins,

can signifi cantly motivate smokers to kick

the habit and yield positive economic benefi ts. [J Gen Intern Med 2024;39:1721-1734;

Pharm World Sci 2007;29:101-103] The

success rates vary between 29.1 percent

and 42.6 percent, indicating that the road to

smoking cessation is rarely a straight line. [J

Prof Mohammad Haniki

Guardians of oral health

Periodontal diseases, such as gingivitis

and periodontitis, can lead to a cascade of

problems, such as diabetes, cardiovascular disease, adverse pregnancy outcomes,

osteoporosis, and respiratory diseases. [J

Pharm Bioallied Sci 2012;4:S280-S282;

Front Cardiovasc Med 2021:7:625579;

Healthcare 2023;11:1372 Jpn Dent

Sci Rev 2021:57:201-208; J Med Life

2013;6:244-248]

“There are about 800 species of

bacteria in the mouth,” Dr Heng shared.

“If the bacteria move into the bloodstream, the bloodstream itself will bring

the bacteria to all body parts.”

To prevent periodontal diseases, Dr Heng

underscored the importance of brushing the

teeth properly, fl ossing or using an interdental brush, and rinsing with an antimicrobial

mouthwash. “Visit the dentist regularly, at

least once every 6 months. With professional

cleaning, stubborn tartar and plaque can be

removed from the teeth, which can be diffi cult

to do with a toothbrush.”

Building upon the foundation of good

oral hygiene, he said pharmacists can play

a role in promoting oral health and preventing dental caries and periodontal diseases.

They provide dietary recommendations

and advice on topical fl uorides and soft

fi lament toothbrushes, including the

benefi ts of dental services and preventive therapeutic measures. [Br Dent J

2015;218:E10; Pharm Times 2006;2:65-

67; Dent Update 2008;35:460-462]

Brush,

fl oss, rinse

Clin Diagn Res 2016;10:LC11-LC15; Can

Pharm J (Ott) 2016;149:303-312]

Prof Haniki stressed the complexities

of smoking cessation, which is often infl uenced by multiple factors, including smokers’ commitment to quitting, the availability

of medications such as nicotine replacement therapy, medication cost, the zoning of

community pharmacies, and public awareness, among others. [J Pharm Health Serv

Res 2017;8:201-208; BMC Health Sev Res

2021;21:822] Given these factors, he said

continuous education and training of pharmacists are imperative to provide the most eff ective support to smokers in their quit journey.

39

DOCTOR | NOVEMBER ISSUE

FOCUS ON ANTIMICROBIAL RESISTANCE

Antimicrobial resistance (AMR) is a global public health concern

that threatens the ability to treat bacterial infections successfully.

When bacteria, fungi, and parasites no longer respond to

antimicrobial agents, treatments become infective and infections

become increasingly diffi cult or impossible to treat, increasing the

risk of severe illness and death.

The World AMR Awareness Week, celebrated from November

18–24 every year, aims to encourage best practices to reduce

the further emergence and spread of AMR. This year’s theme is

“Educate. Advocate. Act now.”

MIMS Doctor joins the global medical community in raising

awareness and understanding of AMR to reduce drug-resistant

infections.

World

Antimicrobial

Resistance

Awareness Week

November 18-24

40

DOCTOR | NOVEMBER ISSUE

FOCUS ON ANTIMICROBIAL RESISTANCE

Over 39M people could die

from superbugs by 2050

ELVIRA MANZANO

More than 39 million people

worldwide could die from antibiotic-resistant infections from

2025 to 2050 as the superbug crisis intensifi es, according to a new global analysis of antimicrobial resistance.

By 2050, annual death tolls attributed to or associated with antibiotic resistance will reach 1.91 million and 8.22

million, respectively, if remediation measures are not put in place. [Lancet 2024;

404(10459):1199-1226]

“Those numbers represent increases

of nearly 68 percent and 75 percent per

year, respectively, compared with death

tolls attributed to antibiotic resistance in

2022,” said researchers who conducted

the study. “Older people are most at risk,

roughly driving the increase in fatalities.”

They forecasted the increase in

death tolls would strain health systems

and national economies and contribute

to annual gross domestic product losses

of $1 trillion to $3.4 trillion by 2030.

Resistant microbes

Antimicrobial resistance (AMR) occurs when pathogens like bacteria, fungi, and parasites evolve and no longer

respond to medications that

kill them, making infections

more challenging to treat.

“It’s a big problem that

is here to stay,” said senior author of the study, Dr

Christopher Murray, director of the Institute for Health

Metrics and Evaluation at the

University of Washington in

Seattle, Washington, US.

The study, conducted as part

of the Global Research on Antimicrobial Resistance Project, involved 500 researchers and is the fi rst to analyse global AMR trends over time. Estimates were

made for 22 types of disease-causing

organisms, 84 combinations of drugs vs

bacteria, and 11 infectious syndromes

such as meningitis and sepsis.

About 520 million datasets were

examined, including hospital discharge

records, insurance claims, and death

certifi cates from 204 countries and territories. Using statistical modeling, they

found that more than 1 million deaths

related to AMR occurred each year from

1990 to 2021. Forecasts are running

through 2050.

3 deaths every minute

Professor Kevin Ikuta, lead author of

the study and clinical infectious diseases physician at the University of California Los Angeles in California, US, said

the projected 39 million deaths equate

to about three per minute. An estimated 11.8 million deaths will be in South

Asia. Deaths from AMR will also be high

in eastern Asia and sub-Saharan Africa.

“Between 1990 and 2021, children

≤5 years saw a more than 50 percent

decrease in AMR deaths, whereas seniors aged ≥70 saw an increase of more

than 80 percent,” he shared. “Deaths

among children will continue to decline,

halving by 2050, but deaths will double

among seniors over the same period.”

As the global population ages, AMR

deaths among seniors may soon outpace those in other age groups, Ikuta

warned.

Over 39M people could die

from superbugs by 2050

respond to medications that

kill them, making infections

more challenging to treat.

is here to stay,” said senior author of the study, Dr

Christopher Murray, director of the Institute for Health

Metrics and Evaluation at the

University of Washington in

Seattle, Washington, US.

The study, conducted as part

of the Global Research on Antimicrobial Resistance Project, involved 500 re-

“Increasingly, we’re seeing that antibiotics are being overused or misused,

which puts more pressure on bacteria

to become more resistant with time,” he

added.

In one study, for example, 1 in 4

hospitalized children in the US was prescribed antibiotics suboptimally. Reasons for inappropriate use included a

bug-drug mismatch, surgical prophylaxis, overly broad empiric therapy, and

unnecessary treatment. [Clin Infect Dis

2020;71:e226-e234]

The WHO said AMR makes common

infections harder to treat and medical interventions, such as chemotherapy and

caesarean sections, riskier.

Hence, the researchers advocate for

better access to healthcare, new vaccines and antibiotics, and judicious antibiotic use protocols to stem the tide of

AMR and save lives globally.

Murray said fi ghting AMR will require teamwork. “We can’t do this on a

piecemeal. We need a concerted global

eff ort.”

“Increasingly, we’re

seeing that antibiotics

are being overused or

misused, which puts

more pressure on

bacteria to become more

resistant with time”

NEWSBITES

41

DOCTOR | NOVEMBER ISSUE

STEPHEN PADILLA

I

ntense rainfall appears to contribute

to a higher risk of death from all causes and cardiovascular or respiratory

causes, suggests a study. This association varies with local climate and urban

infrastructure.

“The signifi cant eff ects of extreme

events were modifi ed by climate types

and were most pronounced in locations

characterized by low variability in precipitation or scarce vegetation coverage,”

the investigators said.

More than 600 locations across

34 countries or regions were included

in this two-stage time series analysis.

Using daily mortality data consisting of

109,954,744 all-cause, 31,164,161 cardiovascular, and 11,817,278 respiratory

deaths from 1980 to 2020, the investigators examined the association between daily mortality and rainfall events

with return periods of 1, 2, and 5 years,

with a 14-day lag period.

Return period was defi ned as the

expected average time between occurrences of an extreme event of a certain

magnitude. A continuous relative intensity index was applied to create intensity-response curves that estimated mortality risks on a global scale.

There were 50,913 rainfall events

with a 1-year, 8,362 events with a 2-

year, and 3,301 events with a 5-year

return period identifi ed during the study

period. [BMJ 2024;387:e080944]

A day of extreme rainfall with a 5-

year return period signifi cantly correlated with an elevated daily all-cause (cumulative relative risk [RR] across 0–14

lag days, 1.08, 95 percent confi dence

interval [CI], 1.05–1.11), cardiovascular

(RR, 1.05, 95 percent CI, 1.02–1.08),

and respiratory (RR, 1.29, 95 percent

CI, 1.19–1.39) mortality.

On the other hand, rainfall events

with a 2-year return period correlated

with respiratory deaths only, while no

signifi cant associations were observed

for rainfall events with a 1-year return

period.

In nonlinear analysis, the protective eff ects (RR <1) seen with moderate-to-heavy rainfall turned into adverse

eff ects (RR >1) when rainfall intensity

became extreme.

Notably, climate type, baseline variability in rainfall, and vegetation coverage appeared to modify the mortality

risks associated with extreme rainfall

events. On the contrary, population

density and income level showed nonsignifi cant moderating eff ects. Additionally, locations with lower variability

of baseline rainfall or scarce vegetation

were at increased risks.

Mechanism

“Although the biological mechanisms linking rainfall intensity with

health outcomes are not fully elucidated, several plausible explanations may

be helpful to clarify the complex association observed in our study,” the investigators said.

For instance, moderate-to-high rainfall intensity may have protective eff ects

because of the improvement in air quality (rainfall can reduce concentrations

of PM2.5 particles in the atmosphere)

and changes in the behaviour (rainfall

may alter people’s daily pattern, leading to more time spent indoors). [Earth

Space Sci 2019;6:1915-1925; PLoS

One 2013;8:e81153]

“This reduction in direct exposure

to outdoor air pollution and nonoptimal

temperatures could explain the protective eff ect observed on various health

outcomes when intensity is not extreme,” the investigators said.

Moreover, as rainfall intensity increases, the initial protective eff ects

may be infl uenced by several negative

impacts, namely critical disruptions to

resources, physiological impacts, and

indirect eff ects.

“These fi ndings underscore the need

for comprehensive public health strategies, developed through collaboration

among meteorological, public health,

and urban planning sectors,” the investigators said.

“Such strategies are crucial to mitigate the broad health eff ects of extreme

rainfall. This is especially important considering the well-established trend of increasing short-term rainfall intensity as a

result of climate change,” they added.

Extreme rainfall puts people’s lives at risk

NEWSBITES

In utero exposure to fl u spells increased risk

of childhood seizures

DOCTOR | NOVEMBER ISSUE

JAIRIA DELA CRUZ

I

nfants born to mothers who contracted

infl uenza infection during pregnancy are

at heightened risk of seizures, particularly febrile seizures, during childhood,

according to a large study.

Analysis of data from more than 1

million mother-off spring pairs from Taiwan’s Maternal and Child Health Database showed that the cumulative risk

of seizures was elevated among off -

spring whose mothers had prenatal infl uenza infection than among off spring

whose mothers had not been exposed

to such infection during pregnancy (all

seizures: adjusted hazard ratio [aHR],

1.09, 95 percent confi dence interval [CI],

1.05–1.14; p<0.001). [JAMA Netw Open

2024;7:e2434935]

When stratifi ed by seizure type, in

utero exposure to infl uenza raised the risk

of febrile convulsions by 11 percent (aHR,

1.11, 95 percent CI, 1.06–1.17; p<0.001)

but not the risk of epilepsy (aHR, 1.04, 95

percent CI, 0.97–1.13; p=0.27).

Looking at the timing of infl uenza infection, the investigators noted a slight

increase in the risk of all seizures, febrile

convulsions, and epilepsy during the third

trimester, although this risk increase was

not signifi cant.

Several factors infl uenced the risk

of all seizures among children born to

mothers who had infl uenza during pregnancy. These included maternal age

(25–29 vs <25 years: aHR, 0.90, 95 percent CI, 0.86–0.94; p<0.001), gestational hypertension (aHR, 1.78, 95 percent

CI, 1.18–2.69; p<0.001), mode of delivery (caesarean delivery: aHR, 1.09, 95

percent CI, 1.05–1.14; p<0.001), male

off spring sex (aHR, 1.28, 95 percent

CI, 1.23–1.32; p<0.001), birth weight

(2,000–2,499 vs ≥2,500 g: aHR, 1.27,

95 percent CI, 1.17–1.38; p<0.001), and

gestational age (32–36 vs ≥37 weeks:

aHR, 1.23, 95 percent CI, 1.14–1.33;

p<0.001).

The fi ndings were robust to sensitivity

analyses adjusted for maternal age, family income, urbanization, or pregnancy-related complications.

This study aligns with an international

study wherein prenatal exposure to infl uenza infection was also associated with

increased risk of childhood seizures (HR,

1.17, 95 percent CI, 1.07–1.28), including febrile seizure (HR, 1.20, 95 percent

CI, 1.07–1.34) but not epilepsy (HR,

1.07, 95 percent CI, 0.81–1.41), according to the investigators. [Arch Dis Child

2022;107:153-159]

“During pregnancy, it is broadly believed that a state of generalized immunosuppression develops, which makes

the mother more susceptible to certain

infectious diseases. These pathogens

may have unfavourable foetal and neonatal consequences, due to intrauterine

transmission via the placenta,” the investigators noted.

In animal studies, “general infl ammatory changes in vessels, vascular

dysfunction, with increased proinfl ammatory cells and cytokines were found

in pregnant mice with infl uenza A virus

infection. This phenomenon can lead

to poor placental maturation, restricted

foetal growth, and molecular evidence of

foetal brain hypoxia … Hypoxia-aff ected

grey matter is more electrosensitive and

could precede a seizure attack,” they

pointed out. [Proc Natl Acad Sci U S A

2020;117:24964-24973]

The investigators highlighted the mentioned evidence as a possible explanation

for the higher risk of seizures observed

among children born to mothers who

contracted infl uenza during pregnancy.

“Further studies are needed to elucidate the mechanisms underlying childhood

neurological development,” they said.

The study included 1,316,107 mother-off spring pairs, 75,835 off spring (51.9

percent male) of whom were born to mothers (predominant maternal age 25–29

years) who had infl uenza during pregnancy. Compared with mothers without a history of prenatal infl uenza infection, those

who did had a slightly higher prevalence

of placenta praevia or placental abruption

(1.6 percent vs 1.4 percent; p<0.001).

42

NEWSBITES

43

DOCTOR | NOVEMBER ISSUE

Happiness key to a healthy heart

AUDREY ABELLA

An analysis using the UK Biobank

dataset shows a robust inverse

association between well-being and risk of cardiovascular diseases (CVDs), underpinning the protective

eff ect of higher well-being on the four

major CVDs evaluated: coronary heart

disease, myocardial infarction (MI), heart

failure (HF), and stroke.

“Emerging evidence suggests a potential protective role of well-being in

reducing CVD risk … [As such,] we assessed the well-being of participants using

a well-being index derived from baseline

questionnaires,” said the researchers.

The well-being index is a validated, reliable measure of subjective well-being.

[Transl Psychiatry 2022;12:113]

“[Our study showed that the] well-being index longitudinally predicts CVDs …

[E]ach 1-SD increase in the well-being

index [was] associated with a reduced

risk of CVDs,” they said.

In model 1*, a higher well-being index

was tied to reduced CVD risk, with hazard ratios (HRs) ranging from 0.79 to

0.86. This inverse association was upheld

in models 2* (HRs from 0.81 to 0.88) and

3* (HRs from 0.83 to 0.90). [J Am Heart

Assoc 2024;13:e035225]

A sex-based comparison revealed a

marginally higher average score in women

vs men (0.023 vs ?0.029; Wilcoxon

p=1.140×10?16). “We observed that happiness, while acting as a protective factor

against almost all four CVD outcomes,

showed a reduced eff ect in men. This

could be linked to the generally lower baseline levels of happiness in men compared

with women,” the researchers explained.

“Sociocultural norms and expectations regarding sex roles might play a

signifi cant role here,” they added. Men

may be emotionally withdrawn owing to

the societal construct depicting men as

more impassive than women. [The Gendered Landscape of Suicide: Masculinities, Emotions, and Culture 2019:61–95]

In the latent class analysis that identifi ed four distinct well-being classes (low,

moderate-to-high, high, variable satisfaction), higher satisfaction levels generally correlated with lower risk of CVDs

than the low-satisfaction group (HRs

from 0.44 to 0.56).

Of note, participants in the moderate-to-high-satisfaction group – despite

occasionally achieving the ‘extremely

happy’ level – did not consistently sustain

high satisfaction across all dimensions of

well-being. They had higher CVD risks

than the high-satisfaction group, who

were generally in a ‘very happy’ state

across a more balanced range of dimensions. “This fi nding highlights the importance of a holistic approach to well-being, considering multiple dimensions to

assess an individual’s overall state,” the

researchers said.

A viable target for CVD

prevention

The study cohort comprised 121,317

participants (mean age 56.56 years, 55

percent women). Over a median follow-up

period of 11.77 years, various CVD cases

were recorded: chronic ischaemic heart

disease (n=9,177), MI (n=6,462), stroke

(n=5,990), and HF (n=3,323).

“In light of the generally irreversible

nature of most CVDs, primary prevention

has become a critical approach in maintaining CV and cerebrovascular health,”

said the researchers. “The fi ndings underscore the importance of incorporating

well-being enhancement strategies into

public health initiatives aimed at reducing

CVD risk.”

However, some outcomes were

self-reported, which might have introduced biases. The predominantly White

lineage and participants belonging to

more affl uent and healthier UK neighbourhoods also limit the generalizability

of the fi ndings.

Despite the limitations, the large sample size, long follow-up, and several CVD

outcomes evaluated may have contributed to the strong inverse relationship between well-being and CVD risk.

“Understanding this relationship could

aid in identifying at-risk populations and

devising intervention strategies to enhance

well-being, potentially reducing the incidence of CV and cerebrovascular diseases,” the researchers concluded.

*Model 1: adjusted for age, sex, ethnicity, hypertension,

diabetes, dyslipidaemia, estimated glomerular fi ltration

rate, medications; model 2: further adjusted for BMI,

smoking status, alcohol consumption; model 3: additionally adjusted for history of cancer, asthma, bronchiectasis, or chronic obstructive pulmonary disease

RESEARCH REVIEW

44

DOCTOR | NOVEMBER ISSUE

Hearing loss a

red fl ag for PD

Hearing loss appears to raise the

risk of later development of Parkinson’s disease (PD). The good

news is that the risk may be attenuated by

using hearing aids, according to a study.

Researchers used data from the

US Department of Veterans Aff airs of

3,596,365 individuals (mean age 67 years,

96 percent) with audiogram results.

Of the participants, 750,010 (20.8

percent) had normal hearing (<20 dB),

1,080,651 (30 percent) had mild hearing loss (20 to <35 dB), 1,039,785 (28.9

percent) had moderate hearing loss (35

to <50 dB), 568,296 (15.8 percent) had

moderate-to-severe hearing loss (50 to

<65 dB), and 157,623 (4.3 percent) had

severe-to-profound hearing loss (65-

120 dB).

Over a mean follow-up of 7.6 years,

the incidence rate of PD ranged from 3.69

to 11.6 per 10,000 person-years, with

rates increasing as the severity of hearing

loss increased. At 10 years, the number of

additional cases of PD was 6.1 in the mild

hearing loss group, 15.8 in the moderate

hearing loss group, 16.2 in the moderate-to-severe hearing loss group, and 12.1

in the severe-to-profound hearing loss

group vs those who had normal hearing.

When combined with established

prodromal conditions, hearing loss was

associated with 5.7 additional cases of

PD at 10 years vs either condition alone.

However, prompt use of hearing aids

was associated with a reduction in PD

incident cases by 21.6 cases.The fi ndings highlight the importance of widespread screening for hearing loss and

prompt use of hearing aids to reduce the

incidence of PD.

Neilson L, et al. Hearing Loss, Incident Parkinson

Disease, and Treatment With Hearing Aids.JAMA Neurol

2024;doi:10.1001/jamaneurol.2024.3568.

Curcuma supplements

benefi cial for AMD?

Curcuma-based nutritional supplements (CBNS) may help reduce the risk

of incident age-related macular degeneration (AMD) or progression to

the late stages of AMD, as shown in a retrospective study.

Researchers identifi ed patients with a history of AMD in the TriNetX datasets

who had CBNS prescription records and compared them with those without

AMD or CBNS prescription records. Propensity score matching (PSM) was

used to control for baseline demographics and medical comorbidities.

Main outcome measures included the incidence of nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requirement for intravitreal antivascular endothelial growth factor (anti-VEGF) therapy.

A total of 66,804 participants in the CBNS cohort (mean age 64.9 years,

66.1 percent female) and 1,809,440 (mean age 67.0 years, 55.2 percent female) in the comparator cohort were identifi ed. After PSM, 66,799 participants

in each cohort were included in the analyses.

In the subgroup of participants who were 50 years of age, CBNS use was

associated with a lower risk of nonexudative AMD (relative risk [RR], 0.23;

p<0.001), advanced nonexudative AMD or GA (RR, 0.11; p<0.001), exudative

AMD (RR, 0.28; p<0.001), blindness (RR, 0.46; p<0.001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; p<0.001) compared with nonuse. The fi ndings

were similar for the subgroup of participants aged ≥60 and ≥70 years.

In patients with early nonexudative AMD, CBNS use reduced the risk of

progression to advanced nonexudative AMD or GA by 42 percent compared

with nonuse (RR, 0.58; p<0.001).

Alsoudi A, et al. Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration.

JAMA Ophthalmol 2024;doi:10.1001/jamaophthalmol.2024.4400

CLINICAL INSIGHTS | DEVICE

45

DOCTOR | NOVEMBER ISSUE

What educational topics on smartphone

apps matter to RMD patients

STEPHEN PADILLA

A mong the many educational topics and functions available in a

smartphone app, the ones considered most important by patients with

rheumatic and musculoskeletal diseases (RMD) include symptom monitoring

and information about laboratory test

results, medications, and disease, reports a study.

“This guidance can be used to create educational and digital tools to support people living with rheumatic diseases during their disease journey and to be

responsive to data provided by patients

and their doctors,” the investigators said.

Nominal group techniques with RMD

patients were carried out using online

tools to come up with a list of needed

educational topics.

Based on the gathered results, the

investigators administered an online survey with fi nal educational items, along

with questions about desired functions

of a smartphone app for RMD and wearable use, to patients in a community

rheumatology practice-based research

network and the PatientSpot registry.

Finally, diff erences in priorities between groups of respondents with rheumatic infl ammatory conditions (RICs)

and osteoarthritis (OA) and possible

associations using chi-square tests and

multivariate regression models were

looked into.

Nearly four in fi ve respondents

deemed fi nding a rheumatologist, understanding tests and medications, and

quickly recognizing and communicating symptoms to doctors as “extremely

important” educational topics. Specifi -

cally, “knowing when the medication is

not working” was the topic ranked the

highest by both RIC and OA groups. [J

Rheumatol 2024;51:904-912]

“This guidance can

be used to create

educational and digital

tools to support people

living with rheumatic

diseases during their

disease journey”

Among the smartphone app functions, those considered by most respondents as useful were viewing laboratory

results, recording symptoms to share

with their rheumatology provider, and

recording symptoms (eg, pain, fatigue)

or disease fl ares for health tracking over

time. About one in three of the respondents owned and regularly used a wearable activity tracker.

“Among the few diff erences between

respondents with RIC vs OA, those with

RIC were less likely to rate knowing

about all medication or other therapy

options, including alternative treatments

such as acupuncture, as extremely important,” the investigators said.

“This perhaps refl ects the dearth

of available pharmacological therapies

currently available for OA and indicates

a desire among people with OA to be

better informed about options to address the pain and limited mobility that

accompany OA,” they added.

Patient education

“Eff ective patient education with durable benefi ts is important for shared

decision making, patient-centred care,

and involving patients in patient-centred

outcomes research,” they said.

However, more and more people

with chronic diseases, including RMD,

are seeking information online or trying

to educate themselves without the guidance of a healthcare professional. [Digit

Health 2019;5:2055207619888073]

“Ultimately, further research using

these patient-generated topics is warranted to determine whether eff ective

dissemination of patient education using

the words and priorities of people living with rheumatic conditions positively

aff ects outcomes, including treatment

adherence, quality of life, patient-centredness, and health outcomes,” the investigators said.

CLINICAL INSIGHTS | DEVICE

46

DOCTOR | NOVEMBER ISSUE

Handheld skin analysis device delivers

reliable skin age, health readings

JAIRIA DELA CRUZ

A novel handheld device can measure age-related skin parameters,

including facial age, wrinkles, and

skin evenness, with an accuracy similar to that of other well-established skin

analysis devices in a study.

Named Skinly, the device employs a

multiparametric approach to analyse the

skin’s properties, according to Germany-based researchers who developed

the device.

The device equips a moisture sensor and camera with three diff erent light

sources: nondirect, cross-polarized, and

short wavelength light exciting skin fl uorescence. The moisture sensor is calibrated to the maximum range by measuring air and wet tissues (0–100 au) as

well as dry and moisturized skin. Meanwhile, the camera harnesses macro-optics capable of taking close-up images of

the skin, especially the cheek, the corner

of the eye, the forehead, and the area

above the wrist.

An accompanying smartphone software application assists device users

during measurements. The application

can be used to document data regarding

sleep, nutrition, special skin conditions,

or menstrual cycle. It also has a geolocation capability, which allows evaluation

of local environmental conditions that

may infl uence skin health such as temperature, humidity, pollen count, and the

ultraviolet index.

Testing and validation

Computer algorithms facilitate the

measurement of skin parameters. These

algorithms were constructed using data

from participants (18-60 years, 90 percent women), majority of whom were

Caucasians and Asians.

Measurements for facial age (validation dataset, n=9,657), skin evenness

(validation dataset, n=9,597), and wrinkle

depth (validation dataset, n=9,704) were

validated using measurements by device

users at home, whereas those for glossiness, redness, skin tone, and porphyrin

levels were validated using data obtained

from investigator assessment of skin at

the laboratory or in vitro tests.

“To cope with the expected data

volumes and their complexity, we incorporated modern data handling and data

processing infrastructures based on

cloud computing,” the researchers said.

There was a high correlation between the assigned facial age, predicted by the facial age algorithm from the

images taken by Skinly, and the participants’ actual age. [Skin Res Technol

2024;30:e13613]

“It is important to note that the objective of the device is not to predict the

calendric age of a person but the assigned/apparent age such that it is possible to identify slow and fast agers,” the

researchers noted.

Likewise, the device was able to capture an increase in the density and length

of deep wrinkles and a decrease in general evenness of cheek skin with rising age.

Measurements taken with the Skinly device also correlated with those obtained with available well-established

instruments, such as the Glossymeter

for glossiness (r=0.93, n=17), Visiopor for

porphyrin fl uorescence (r=0.96, n=15),

Colorimeter and Spectrophotometer for

skin tone (r=0.99 for both).

Taken together, the fi ndings point to

the potential of Skinly to replace more

expensive, time-consuming diagnostic

tools, according to the researchers, who

believe that the device will prove valuable

in dermatological research, off ering a reliable, versatile tool for comprehensive

skin analysis.

“The fi ndings point to

the potential of Skinly to

replace more expensive,

time-consuming

diagnostic tools”

CALENDAR

47

DOCTOR | NOVEMBER ISSUE

*For updates, please refer to the conference websites.

American Association for the

Study of Liver Diseases (AASLD):

The Liver Meeting

Location: San Diego, California, US

Email: meetings@aasld.org

Website: https://www.aasld.org/the-livermeeting

NOVEMBER

15-19

FRIDAY – TUESDAY

The 25th Congress of the Asian

Society for Vascular Surgery

(ASVS)

Location: Bangkok, Thailand

Email: info@asvs2024.com;

asvs2024secretary@gmail.com

Website: https://asvs2024.com

DECEMBER

3-6

TUESDAY – FRIDAY

European Society for Medical

Oncology (ESMO) Asia Congress

Location: Singapore

Tel: 41 0 91 973 19 00

Fax: 41 0 91 973 19 02

Email: esmo@esmo.org; asiacongress@esmo.

org; registration@esmo.org

Website: https://www.esmo.org/meetingcalendar/esmo-asia-congress-2024

DECEMBER

6-8

FRIDAY – SUNDAY

The 66th American Society

of Hematology (ASH) Annual

Meeting & Exposition

Location: San Diego, California, US | Online

Tel: 202 776 0544; 866 828 1231

Fax: 202 776 0545

Email: customerservice@hematology.org

Website: https://www.hematology.org/

meetings/annual-meeting

DECEMBER

7-10

SATURDAY – TUESDAY

Advances in Infl ammatory Bowel

Diseases (AIBD)

Location: Orlando, Florida, US

Tel: 610 560 0500

Fax: 610 560 0502

Website: https://www.hmpglobalevents.com/

aibd

DECEMBER

9-11

MONDAY – WEDNESDAY

San Antonio Breast Cancer

Symposium (SABCS)

Location: San Antonio, Texas, US

Tel: 210 450 1550

Email: sabcs@uthscsa.edu

Website: https://sabcs.org

DECEMBER

10-13

TUESDAY – FRIDAY

The American Heart Association

(AHA) Scientifi c Sessions 2024

Location: Chicago, Illinois, US

Tel: 1 508 743 8517; 1 888 242 2453;

214 570 5935

Email: sessions@xpressreg.net;

Scientifi cConferences@heart.org

Website: https://professional.heart.org/en/

meetings/scientifi c-sessions

NOVEMBER

16-18

SATURDAY – MONDAY

Asian Pacifi c Digestive Week

(APDW)

Location: Bali, Indonesia

Tel: 65 6346 4402

Email: secretariat@apdw2024bali.com;

registration@apdw2024bali.com

Website: https://www.apdw2024bali.com

NOVEMBER

21-24

THURSDAY – SUNDAY

American Society of Clinical

Oncology Gastrointestinal Cancers

Symposium (ASCO GI)

Location: San Francisco, California, US | Online

Tel: 571 483 1300; 888 788 1522; 703 449 6418;

888 282 2552; 703 299 0158

Email: giregistration@spargoinc.com;

customerservice@asco.org

Website: https://conferences.asco.org/gi/attend

JANUARY 2025

23-25

THURSDAY – SATURDAY

CALENDAR

48

DOCTOR | NOVEMBER ISSUE

*For updates, please refer to the conference websites.

Society for Maternal-Fetal

Medicine (SMFM) 45th Annual

Pregnancy Meeting

Location: Denver, Colorado, US

Email: events@smfm.org; smfm@smfm.org

Website: https://smfm2025.eventscribe.net

JANUARY – FEBRUARY 2025

27-1

MONDAY – SATURDAY

International Master Course

on Aging Science (IMCAS)

World Congress

Location: Paris, France

Tel: 33 1 40 73 82 82

Email: contact@imcas.com

Website: https://www.imcas.com/en/attend/

imcas-world-congress-2025

JANUARY – FEBRUARY 2025

30-1

THURSDAY – SATURDAY

International Stroke

Conference (ISC)

Location: Los Angeles, California, US | Online

Tel: 1 508 743 8517; 1 888 242 2453;

214 570 5935

Email: InternationalStroke@xpressreg.net;

Scientifi cConferences@heart.org

Website: https://professional.heart.org/en/

meetings/international-stroke-conference

FEBRUARY 2025

5-7

WEDNESDAY – FRIDAY

Crohn’s & Colitis Congress

Location: San Francisco, California, US

Tel: 800 932 2423

Email: info@crohnscolitiscongress.org

Website: https://crohnscolitiscongress.org

FEBRUARY 2025

6-8

THURSDAY – SATURDAY

American Academy of Allergy,

Asthma & Immunology (AAAAI)

Annual Meeting / World Allergy

Organization (WAO) Joint Congress

Location: San Diego, California, US

Tel: 414 272 6071

Fax: 414 272 6070

Email: annualmeeting.aaaai.org

Website: https://annualmeeting.aaaai.org

FEBRUARY– MARCH 2025

28-3

FRIDAY – MONDAY

American Academy of

Dermatology (AAD) Annual Meeting

Location: Orlando, Florida, US

Tel: 847 240 1280

Fax: 847 240 1859

Email: mrc@aad.org

Website: https://www.aad.org/member/

meetings-education/am25

MARCH 2025

7-11

FRIDAY – TUESDAY

The 32nd Conference on

Retroviruses and Opportunistic

Infections (CROI)

Location: San Francisco, California, US

Tel: 415 544 9400

Website: https://www.croiconference.org

MARCH 2025

9-12

SUNDAY – WEDNESDAY

ASCO Genitourinary Cancers

Symposium (ASCO GU)

Location: San Francisco, California, US | Online

Tel: 571 483 1300; 888 788 1522; 703 449 6418;

888 282 2552; 703 299 0158

Email: guregistration@spargoinc.com;

customerservice@asco.org

Website: conferences.asco.org/gu/attend

FEBRUARY 2025

13-15

THURSDAY – SATURDAY

The 13th Asia-Pacifi c Breast

Cancer Summit (APBCS)

Location: Singapore

Tel: 971 4 520 8888

Email: info@apbcs.org

Website: https://apbcs.org

FEBRUARY 2025

21-23

FRIDAY – SUNDAY

HUMOUR

49

DOCTOR | NOVEMBER ISSUE

Hey, mister! You dropped

your head back there!”

“You can’t have another coronary

artery bypass operation until you’ve

fi nished paying for the last two!”

“Is it my eyes or your

goiter that is getting bigger?”

“It’s called the widow’s

guide to dating!”

“Give me a hand here, Miss Duval. I think

I caught the bug that’s been going around!”

“OK, one more time and it’s off to sleep ...

Hey tiger, do you want to have some fun?”