Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement

Background: The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and longterm control. Objectives: The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. Methods: Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability, and feasibility to be considered for the final COS. Results: At the 4th international HOME meeting there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure (POEM) should be used as the core instrument (87.5% agreed, 9.4% unsure, 3.1% disagreed). Conclusions: All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM

Patients with atopic dermatitis with filaggrin loss-of-function mutations show good but lower responses to immunosuppressive treatment

Filaggrin (FLG) mutations are a strong risk factor to develop atopic dermatitis (AD). However, the relationship between FLG mutations and treatment outcome in AD has not been thoroughly studied. To investigate whether FLG mutations influence immunosuppressive treatment outcome in AD, we studied the effect of FLG mutations in patients with severe AD participating in a single blinded randomized controlled trial (RCT) with methotrexate (MTX) or azathioprine (AZA) during a 24 weeks treatment regimen.((1)) Two years after randomization buccal mucosa swabs were collected from 36 of the 42 RCT patients (86%) to determine the FLG genotype status (R501X, 2282del4, R2447X, S3247X and 3321delA mutations). This article is protected by copyright. All rights reserve

Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo‐controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ)

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely-used, potent immunosuppressant for AD. CsA is not effective in all patients, and side effects limit its use. Dupilumab, a fully human anti-interleukin (IL)-4 receptor-alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, key drivers of type 2/Th2-mediated inflammation, and is approved in the U.S.A. and the E.U. for the treatment of adults with moderate-to-severe AD. OBJECTIVES: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with AD with inadequate response to/intolerance of CsA, or for whom CsA was medically inadvisable. METHODS: In this 16-week, double-blind, randomized, placebo-controlled, phase 3 trial, patients were randomized 1:1:1 to subcutaneous dupilumab 300 mg weekly (qw):every two weeks (q2w):placebo. All received concomitant medium-potency TCS from Week -2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. RESULTS: 390 patients were screened; 325 were randomized and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients on dupilumab qw+TCS/q2w+TCS achieved ≥75% improvement from baseline in Eczema Area and Severity Index at Week 16 vs placebo+TCS (primary endpoint) (59.1%/62.6% vs 29.6%; P<0.0001 vs placebo+TCS, both doses). Dupilumab qw+TCS/q2w+TCS significantly improved other clinical outcomes and AD symptoms, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QOL). Treatment groups had similar overall rates of adverse events (69.1%/72.0%/69.4%; qw+TCS/q2w+TCS/placebo+TCS) and serious adverse events (1.8%/1.9%/1.9%). Conjunctivitis was more frequent with dupilumab+TCS; skin infections were more frequent with placebo+TCS. CONCLUSIONS: Dupilumab+TCS significantly improved signs and symptoms of AD and QOL in adults with history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified

Novel systemic therapies in atopic dermatitis : what do we need to fulfil the promise of a treatment revolution?

Patients with atopic dermatitis (AD) who do not adequately respond to topical therapy and phototherapy often need systemic immunomodulatory treatment to control their symptoms. Conventional systemic agents, such as ciclosporin, azathioprine, and methotrexate, have been used for decades, but there are concerns about their safety profile. There are now many novel systemic agents emerging through clinical trials, which may have great potential in the treatment of AD. Despite this, there are very few data comparing the performance of these drugs against each other. The purpose of this article is to review the current systemic therapies in AD and present an indirect comparison of systemic AD treatments using effectiveness and safety data from published randomised controlled trials, highlighting important remaining gaps in knowledge. Although the latest developments in systemic AD treatments are exciting and dearly needed, further work is required before the promise of a therapeutic revolution becomes reality