Ruxolitinib Cream in Adolescents/Adults with Atopic Dermatitis Meeting Severity Thresholds for Systemic Therapy: Exploratory Analysis of Pooled Results from Two Phase 3 Studies.

ABSTRACT

INTRODUCTION: Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52 weeks was assessed in a subset of patients with moderate and/or more extensive disease. METHODS: This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. RESULTS: Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week 8 (continuous-use), IGA-treatment success (IGA 0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use week 8) to 18/23 patients (78.3%; as-needed use week 52) in patients applying ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. CONCLUSION: Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. TRIAL REGISTRATION NUMBER NCT03745638/NCT03745651.

Atopic dermatitis (AD) is a skin condition that causes itchy, dry, and inflamed skin. For many people AD is controlled with medication that is applied to the skin. However, for some people medication that is taken orally or injected (i.e., systemic treatment) may be needed. Systemic treatment can sometimes be challenging. Doctors use a variety of tools to measure AD severity and apply standard criteria to help determine if a person should receive systemic treatment. In the TRuE-AD1/TRuE-AD2 clinical trials, itch and inflammation improved in people with mild to moderate AD after they applied ruxolitinib cream twice daily for 8 weeks. When people then applied ruxolitinib cream to areas of AD only when it was needed for another 44 weeks, ruxolitinib cream provided long-term control of their AD. The aim of this analysis was to assess disease control with ruxolitinib cream in people with AD severe enough to meet the standard criteria indicating a need for systemic treatment. In this group, the majority had clear or almost clear skin after applying ruxolitinib cream twice daily for 8 weeks. After 44 weeks of as-needed application of ruxolitinib cream, most people still had clear or almost clear skin. In this group of people who may have otherwise needed treatment with systemic therapy, ruxolitinib cream twice daily for 8 weeks and then as-needed was generally well tolerated. These results show that as-needed ruxolitinib cream may provide long-term control of AD in people who may otherwise have needed systemic therapy.