Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream

J Allergy Clin Immunol. 2020 Feb;145(2):572-582. doi: 10.1016/j.jaci.2019.08.042. Epub 2019 Oct 17.

Abstract

Background: Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.

Objective: We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.

Methods: In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks, then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index at week 4.

Results: All RUX regimens demonstrated therapeutic benefit at week 4; 1.5% BID provided the greatest improvement in Eczema Area and Severity Index (71.6% vs 15.5%; P < .0001) and Investigator's Global Assessment responses (38.0% vs 7.7%; P < .001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P < .0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application-site reactions.

Conclusions: RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated.

Keywords: Atopic dermatitis; CCL17; IgE; JAK inhibitor; Janus kinase; itch; ruxolitinib; topical.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / therapeutic use*
  • Dermatitis, Atopic / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 2 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Pyrazoles / therapeutic use*
  • Skin Cream / therapeutic use
  • Triamcinolone / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • INCB018424
  • Pyrazoles
  • Triamcinolone
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2

Associated data

  • ClinicalTrials.gov/NCT03011892