Durability of Response to Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis After Treatment Discontinuation in a Phase 2b Trial

INTRODUCTION: Multiple clinical trials showed that 12 weeks of abrocitinib monotherapy was safe and effective for the treatment of moderate-to-severe atopic dermatitis (AD). The reversibility of pharmacologic activity after abrocitinib discontinuation was not described. METHODS: This post hoc analysis used data from a phase 2b study to evaluate maintenance of disease control during a 4-week drug-free follow-up period in patients with moderate-to-severe AD treated with once-daily abrocitinib (200 mg/100 mg) or placebo for 12 weeks. Proportions of patients who achieved and maintained 50% or 75% improvement in Eczema Area and Severity Index (EASI-50/EASI-75), an Investigator’s Global Assessment (IGA) score of 0/1, or at least a 4-point improvement in the pruritus numeric rating scale (pruritus NRS4) were determined. Biomarkers of Janus kinase inhibition and AD disease were measured in blood samples. RESULTS: Among week 12 responders to abrocitinib 200 mg, 77.4%, 42.3%, 21.1%, and 42.9% maintained their EASI-50, EASI-75, IGA, and pruritus NRS4 response at week 16; corresponding proportions of week 12 responders maintaining response to abrocitinib 100 mg were 51.9%, 35.0%, 33.3%, and 43.5%, respectively. Four weeks after abrocitinib discontinuation, all AD biomarkers reverted toward baseline levels, with high-sensitivity C-reactive protein and eosinophil percentage demonstrating the most complete recovery in patients treated with abrocitinib versus placebo. CONCLUSION: Abrocitinib discontinuation resulted in rapid reversal of disease control consistent with reversal of suppression of pharmacodynamic and AD-specific biomarkers during the drug-free follow-up period. Maintenance of response was inversely related to the threshold of improvement. Patients with moderate-to-severe AD using continuous abrocitinib therapy would likely have the best long-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02780167. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13555-022-00764-4.