529 - Worsening of itch before flaring in patients with moderate-to-severe atopic dermatitis treated with abrocitinib: a post hoc analysis of the phase 3 JADE REGIMEN trial

Abstract

Abstract Background Patients with atopic dermatitis (AD) often experience a disease course that fluctuates in severity over time, with periods of remission interrupted by flares. Abrocitinib, an oral, once-daily Janus kinase-1 selective inhibitor is approved for the treatment of patients with moderate-to-severe AD. In the phase 3 JADE REGIMEN (NCT03627767) trial, patients achieved an initial response with abrocitinib 200 mg, which was maintained with continued treatment with abrocitinib 200 mg, reduced-dose treatment with abrocitinib 100 mg, or placebo (treatment withdrawal). Following an initial efficacy response, over the 40-week maintenance period some patients across all treatment groups, but predominantly those who switched to placebo, experienced flares, defined as ≥50% loss of Eczema Area and Severity Index response at week 12 and Investigator’s Global Assessment score ≥2, and received rescue therapy. The utility of itch response as a predictor of an upcoming flare in these patients has not yet been determined. Objective To assess itch response before flaring in patients treated with abrocitinib who experienced a flare during the maintenance period of JADE REGIMEN. Methods In JADE REGIMEN, patients aged ≥12 years with moderate-to-severe AD who responded to abrocitinib 200 mg during open-label induction for 12 weeks were randomly assigned 1:1:1 to receive abrocitinib 200 mg, abrocitinib 100 mg, or placebo for up to 40 weeks (maintenance period). Patients who experienced a flare during maintenance received rescue treatment with abrocitinib 200 mg plus topical medicated therapy in an open-label 12-week period. This post hoc analysis evaluated mean itch scores in subsets of patients who did or did not experience flares during the maintenance period. Itch was assessed using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; © 2016 Pfizer Inc. All rights reserved.) itch numerical rating scale (NRS) item which asked patients, “How itchy was your skin over the past 24 hours?” on a scale from 0 (not itchy) to 10 (extremely itchy). PSAAD scores were collected daily via an e-diary during the screening period and from day 1 through the end of study. Daily itch scores were analyzed at baseline (day of randomization to maintenance treatment groups), from 14 days prior to flaring (from day –14 to day –1), and on the day of flare (day 0) in patients who experienced a flare, and at baseline through 274 days post-randomization in patients who did not experience a flare. Results Of 1233 patients treated with abrocitinib 200 mg in the open-label induction period, 798 (65%) achieved response at week 12 and were randomized to abrocitinib 200 mg (n=266), abrocitinib 100 mg (n=265), or placebo (n=267) in the maintenance period. Across all treatment groups, 442 (55%) patients did not experience a flare and 356 (45%) patients experienced a flare during maintenance. Among patients who did not experience a flare, mean PSAAD itch NRS score remained consistently around 2, with a mean score of 1.5 on day 1 of randomization and 2.1 on day 274 post-randomization. Among patients who experienced a flare, mean PSAAD itch NRS score at baseline was 1.8, which increased to 4.4 on day –14 (14 days before flaring) and continued to increase up to the day of flare (day 0 mean score: 6.4). Conclusions After a successful initial response with abrocitinib, mean itch scores remained stable over time among patients who did not flare. Patients who experienced a flare had worsening of itch from 2 weeks before until the onset of flare. Monitoring of itch may predict onset of flares in patients with moderate-to-severe AD and help inform treatment management or optimization to achieve disease control.