Eczema Review: Studies Look at New and Promising Atopic Dermatitis Treatments
Study: Promising Data Presented on Investigational Therapy in Atopic Dermatitis
New positive results from a phase 2b dose-ranging study evaluating upadacitinib, an investigational, once-daily oral Janus kinase1-selective inhibitor, in adult patients with moderate to severe atopic dermatitis (AD) were presented during the “Late-Breaking Research: Clinical Trials” session at the 2018 American Academy of Dermatology (AAD) Annual Meeting in San Diego, California.
In September 2017, positive top-line results from this phase 2b study, including an evaluation of the primary endpoint—mean percent change in Eczema Area and Severity Index (EASI) score at week 16 vs placebo, were released. At the recent AAD session, Emma Guttman-Yassky, MD, PhD, professor of dermatology and immunology, Icahn School of Medicine at Mount Sinai Medical Center, and lead study investigator, noted that across all doses (30/15/7.5 mg once daily), additional exploratory results showed significant reduction of select symptoms of AD in upadacitinib patients, including reduction in itch (pruritus) at week 1 and improvement in the extent and severity of skin lesions at week 2. In addition, the safety profile for upadacitinib was consistent with previously reported results.
“Patients living with atopic dermatitis are seeking relief from the intense itching and skin lesions, which can have a profound impact,” she said. “For this patient population, given the severity of their disease and available targeted therapies, additional options are needed.”
The dose-ranging study is an ongoing 88-week phase 2b, randomized, double-blind, parallel-group, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of upadacitinib in adult patients with moderate to severe AD not adequately controlled by topical treatments, or for whom topical treatments were not medically advisable.
In Period 1, patients were randomized 1:1:1:1 to 1 of 4 treatment groups (3 dosing groups, 30/15/7.5 mg once daily, and 1 placebo group) for 16 weeks. The primary endpoint of the study was mean percentage change from baseline in EASI score at 16 weeks in comparison with placebo. Secondary endpoints included proportion of patients achieving EASI 90, EASI 75, and Investigator’s Global Assessment (IGA) of 0 or 1 and percent change in pruritus/itch Numerical Rating Scale (NRS) from day 1 (baseline) to week 16 in comparison with placebo.
In an exploratory analysis, results at week 2 of treatment with upadacitinib showed all dose groups (30/15/7.5 mg once daily) achieved significant improvement in extent and severity of AD, as measured by the mean percent change in EASI score. Also, results at week 1 showed reduction in itch in patients treated with upadacitinib, as measured by the NRS, Dr Guttman-Yassky reported.
The most common adverse events were upper respiratory tract infection, AD worsening, and acne. Serious adverse events across treatment groups occurred in 0/1/2 patients in the 30/15/7.5 mg groups compared with 1 patient on placebo. No herpes zoster, malignancies, deaths, or cases of pulmonary embolism or deep vein thrombosis occurred in the first 16 weeks of this phase 2b study.
Phase 3 trials of upadacitinib in rheumatoid arthritis, psoriatic arthritis, and Crohn disease are ongoing. It is also being evaluated as a potential treatment for ankylosing spondylitis. According to AbbVie, registration-enabling studies in AD, ulcerative colitis, and giant cell arteritis will begin this year.
In January 2018, the FDA granted Breakthrough Therapy Designation for upadacitinib in adult patients with moderate to severe AD who are candidates for systemic therapy. Breakthrough Therapy Designation is intended to expedite the development and review of medicines with preliminary clinical evidence that indicate that the investigational treatment may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Dr Guttman-Yassky spoke on numerous topics at the AAD meeting including Therapeutic Approach to Severe Chronic Hand and Foot Eczema; The Immune Pathogenesis of AD and Relevance to Therapeutics; and The Translation Revolution in Atopic Dermatitis. She noted, “We are now beginning an exciting path for a new treatment paradigm for our patients with atopic dermatitis.”
Guttman-Yassky, E, Silverberg JI, Thaçi, D, et al. Primary results from a phase 2b, randomized, placebo-controlled trial of upadacitinib for patients with atopic dermatitis. Presented at: 2018 American Academy of Dermatology Annual Meeting; February 16-20, 2018; San Diego, CA.
Biologic Treatment Rapidly Reduces Pruritus
Dupilumab (Dupixent) quickly improved daily pruritus among patients with atopic dermatitis (AD), according to a recent poster study presented at the 2018 American Academy of Dermatology Annual Meeting.
Jonathan I. Silverberg, MD, PhD, MPH, and colleagues conducted a post-hoc analysis using data from 2 identical, randomized clinical trials—SOLO-1 and SOLO-2. In both trials, a total of 1375 adults with moderate to severe AD were randomized to either 300 mg of dupilumab every week or every 2 weeks or placebo. The proportion of patients who achieved a 3-point or greater or 4-point or greater improvement in peak pruritus Numerical Rating Scale (NRS) from baseline to day 28 was assessed as the main outcome.
Compared with placebo, a significantly greater proportion of participants who received dupilumab achieved a 3-point or more or 4-point or more improvement in the pruritus NRS. This response to dupilumab was seen as early as day 3 or 4. In addition, each dupilumab treatment group had a significantly higher proportion of responders compared with placebo through day 28.
At day 28, 38.9% of participants who received dupilumab every week and 38.6% of participants who received dupilumab every 2 weeks achieved a 3-point or more improvement in NRS compared with 14.3% of those who received placebo. Similarly, 28.7% and 24.7% of participants who received dupilumab every week and every 2 weeks, respectively, achieved a 4-point or more improvement in NRS compared with 7.9% of those who received placebo.
The most common adverse events were AD exacerbation, nasopharyngitis, and injection site reaction.
“Based on improvement in worst itch scores, a greater proportion [of participants] with moderate to severe AD treated only with dupilumab monotherapy showed onset of clinically meaningful improvement as early as day 3 or 4 (ie, 2 to 3 days after initiation of treatment) when compared with placebo,” the researchers concluded.
Silverberg JI, Eckert L, Ardeleanu M, et al. Dupilumab treatment induces rapid clinical improvement of itch in patients with moderate to severe atopic dermatitis. Presented at: 2018 American Academy of Dermatology Annual Meeting; February 16-20, 2018; San Diego, CA.
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