WASHINGTON – A substantial proportion of , Andrew F. Alexis, MD, MPH, reported in a late-breaker abstract session at the annual Revolutionizing Atopic Dermatitis conference.
The analysis stratified patients by age – 18-50 and over 50 years – and found that the sustained improvement with the JAK-1 selective inhibitor as monotherapy was seen regardless of age. “In practice, patients who are older tend to have had AD for a longer period of time and tend to be more difficult to treat so it’s reassuring to see that even in the over-50 age group, they show substantial responses, even with more stringent endpoints,” said Dr. Alexis, professor of clinical dermatology at Weill Cornell Medical College, New York.
Dr. Andrew F. Alexis
At week 96, for instance, the proportion of patients who achieved at least a 75% improvement from baseline on the Eczema Area and Severity Index (EASI-75) was 73% with the 100-mg dose and 85% with the 200-mg dose in the younger age group, and 86% and 89%, respectively, in the older age group.
An EASI-90 response – one of the more stringent outcomes – was achieved by 45% and 58% in the 18-50 group and 58% and 73% in the over 50 group (for 100-mg and 200-mg doses, respectively), Dr. Alexis reported.
The interim analysis also showed dose-dependent efficacy overall up to 96 weeks in the younger age group but only up to 48 weeks in the older age group. Response to some outcome measures in patients over age 50 years was “less clearly dose dependent after week 48” than earlier, Dr. Alexis said.
The ongoing JADE EXTEND trial enrolled patients who had participated in the phase 3 JADE clinical trials. This analysis covered 1,309 patients who were enrolled by a September 2021 cutoff. The patient population leaned young: Eighty percent (1,046) were aged 18-50, and 20% (263) were over 50.
Patients who were randomly assigned to abrocitinib 200 mg or 100 mg in the parent trials continued to receive the same dose in JADE EXTEND with blinding maintained. Those who received placebo in the qualifying trial were randomly assigned to abrocitinib 200 mg or 100 mg. And patients from JADE DARE continued with their dosing of 200 mg. Grouping by age for the analysis was made based on the age recorded at the screening visit of the qualifying trial.
IGA, PP-NRS, and DLQI results
At week 96, the proportion of patients 18-50 years of age who achieved the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with at least a 2-grade improvement from baseline was 44% in the 100-mg group and 55% in the 200-mg group. Among patients over 50, these proportions were 51% and 58%, respectively.
The proportion of patients who achieved at least a 4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale (PP-NRS) score was 54% and 66% (on 100 mg and 200 mg, respectively) among those aged 18-50, and 79% and 80%, respectively, among those over 50.
Looking at more stringent outcomes, 26% and 38% in the 18-50 group on 100 mg and 200 mg, respectively, achieved a PP-NRS of 0/1, as did 54% and 44% in the over-50 group.
Lastly, a score of less than 2 on the Dermatology Life Quality Index (DLQI 0/1) was achieved by 32% and 41% of patients aged 18-50 and by 51% and 48% of patients over 50, for the 100-mg and 200-mg doses, respectively.
The decline in dose-dependent efficacy in the older age group after 48 weeks may be due to the smaller sample of older patients and/or the fact that a higher proportion of older patients had moderate baseline disease per their IGA score, versus severe disease, compared with the younger patients, Dr. Alexis said. “We see a skewing toward a bit more severe [disease] in the younger age group compared to the older,” he noted.
Abrocitinib (Cibinqo) is approved for the treatment of moderate to severe AD in adolescents aged 12 and up and adults whose disease is not adequately controlled with other systemic treatments or those for whom the use of these drugs is not advised. It is available in a 50-mg dose for dose adjustments in special populations, but this dose was not studied in the clinical trials, Dr. Alexis noted. The interim analysis did not include safety data.
In a separate presentation in which he reviewed long-term data on AD medications, Raj Chovatiya, MD, PhD, assistant professor of dermatology at Northwestern University, Chicago, said that most patients who meet defined endpoints at week 12 of treatment with abrocitinib maintain that response over time. “By and large, there’s a steep initial rise that flattens over the long run, which is what you want to see. People getting that response are generally staying there over the course of treatment,” he said, referring to the JADE EXTEND data up to week 48.
Dr. Raj Chovatiya
It’s important to also appreciate, however, that the proportion of patients meeting efficacy outcomes in the trials of abrocitinib has grown well beyond 12 weeks, Dr. Chovatiya said.
Pointing to data presented at a 2021 RAD meeting depicting the proportion of 12-week nonresponders achieving a response at weeks 24 and 48 on IGA 0/1, EASI-75, and PP-NRS, Dr. Chovatiya said the level of response grew at both time points. “You’re capturing a chunk of people well beyond the primary endpoint if you keep them on therapy continuously, suggesting that ... we may need to reframe how we’re thinking about oral JAK inhibitors,” he said. “Not only are they rapidly acting, but they are medications that can provide good control and changes in the long run.”
Dr. Alexis and Dr. Chovatiya disclosed ties with Pfizer, which funded the study.