Abrocitinib efficacy dose-dependent, comparable in all AD age teams

The response to abrocitinib treatment in patients with moderate to severe atopic dermatitis (AD) showed dose-dependent consistency across age groups and was comparable in patients 51 years and older, according to the results of a post hoc analysis of four studies.

Abrocitinib (Cibinqo) is a once-daily orally selective Janus kinase 1 inhibitor that has shown good efficacy and safety as monotherapy or in combination with topical therapy for the treatment of patients with moderate to severe AD. The compound was approved in Europe this week for the treatment of moderate to severe AD in adults who are candidates for systemic therapy and is currently under review by the US Food and Drug Administration.

“We know that responses to systemic therapies and adverse events can be different for patients of different ages,” said Andrew F. Alexis, MD, MPH, during a recent abstract session at the Revolutionizing Atopic Dermatitis virtual symposium. “The efficacy and safety of abrocitinib monotherapy were previously evaluated in controlled clinical trials in patients with moderate to severe AD in adolescent and adult subpopulations, in patients with moderate to severe AD.”

Alexis, Professor of Clinical Dermatology at Weill Cornell Medicine, New York City, and colleagues performed a post-hoc analysis of four randomized, double-blind studies that were stratified by age group: 12-17 years, 18-40 years, 41 – 50 years and 51 years and older. The efficacy data were assessed separately for patients in the monotherapy pool and in the JADE COMPARE study. The monotherapy pool comprised patients from a phase 2b study and two phase 3 studies who received abrocitinib 200 mg, abrocitinib 100 mg or placebo as monotherapy for 12 weeks (JADE-MONO-1 and JADE-MONO-2).

The JADE COMPARE pool included patients who received abrocitinib 200 mg, abrocitinib 100 mg, or placebo plus drug-based topical therapy for 16 weeks. Data from patients in all four studies were pooled for analysis of treatment-related adverse reactions. The analyzed efficacy points were the Investigator Global Assessment (IGA) score of 0/1 (clear or almost clear), a 75 percent reduction compared to the baseline value in the Eczema Area and Severity Index (EASI-75) or the Peak Pruritus Numeric Rating Scale Score (PP-NRS4) at week 12 for the monotherapy pool and at week 16 for COMPARE.

In the monotherapy pool, the proportion of patients aged 12–17 years, 18–40 years, 41–50 years and 51 years and older who achieved an IGA 0/1 response after 12 weeks was 31.3%, 40.2%, 43.8%. , and 50.8% (abrocitinib 200 mg); 22%, 23.7%, 22.4% and 40.8% (abrocitinib 100 mg); and 8.7%, 8%, 3.3% and 10% (placebo).

In JADE COMPARE, the proportions of patients aged 18–40 years, 41–50 years, and 51 years and older who achieved an IGA 0/1 response were 50%, 53.2%, and 34.8% (abrocitinib 200 mg); 36.9%, 37.1% and 26.1% (abrocitinib 100 mg); and 12%, 11.8% and 16.7% (placebo) after 16 weeks. Similar trends were observed for EASI-75 and PP-NRS4 responses at 12 weeks.

In all age groups, the most common treatment-related side effects were infection / infestation and gastrointestinal effects; most of the cases were mild or moderate. Nausea was more common in the two younger age groups and was dose-dependent: for abrocitinib 200 mg and abrocitinib 100 mg, the nausea rates were 18.8% and 7.8% in patients aged 12 to 17 years; 17.1% and 6.4% in patients aged 18 to 40 years; and 7.1% and 3.3% in patients 51 years of age and older.

“The efficacy responses in patients 51 years of age and older were similar to those in other age groups,” concluded Alexis, who is also vice chair of diversity and inclusion in the Department of Dermatology at Weill Cornell. “The safety profile was consistent across all age groups and was similar to that previously reported.”

Researchers found that treatment response to abrocitinib “in the absence or presence of drug-based topical therapy was fairly consistent across all age groups, had a similar dose-dependency, and most importantly showed no decreased efficacy in older adults as measured by lesion severity,” the extent of itching and itching after 4 months, “said Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois, who was asked to comment on the study.

“Also, the safety profile was consistent across all adults, although nausea, in particular, was more common in younger age groups, highlighting an area that needs future research,” he added. “Overall, these data show that abrocitinib is associated with similar short-term responses in adulthood and underscores the importance of the JAK-STAT signaling pathway in the underlying pathophysiology of AD in different age groups. It will be interesting to see how these data compare the practice environment with both short- and long-term outcomes in a heterogeneous patient population. “

In the interview, Chovatiya commented that “The next frontier in personalized therapy for AD involves deeper clinical phenotyping of our patients and a better understanding of how efficacy and safety vary between patient populations.” For example, he noted, “AD in earlier than later adulthood may be associated with different clinical signs, symptoms, comorbidities, and other measures of patient exposure and thus with different treatment responses to systemic therapy.”

Alexis announced that he has worked as a consultant for Leo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Valeant, L’Oreal, BMS, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan or has received consulting fees, Almirall, AbbVie, Sol-Gel, and Amgen.

Chovatiya announced that he is an advisor, speaker and / or member of the advisory boards of AbbVie, Arena, Arcutis, Incyte, Pfizer, Regeneron and Sanofi-Genzyme.

Revolutionizing Atopic Dermatitis Symposium: Presented December 13, 2021. Abstract 584, poster

Doug Brunk is a San Diego-based, award-winning reporter for MDedge and Medscape who began reporting on healthcare in 1991. He is the author of two books on the University of Kentucky Wildcats men’s basketball program.