Concomitant use of apremilast and dupilumab may be effective for patients with moderate to severe atopic dermatitis, according to the results of a study outlined in a letter to the editor published in the Journal of the European Academy of Dermatology and Venereology.
According to the study authors, “While apremilast monotherapy in AD was unsuccessful at significantly improving patients at the FDA approved dose of 30 milligrams (mg) twice daily, a trend toward Eczema Area and Severity Index (EASI) improvement was observed at week 12,” as reported in a previous study. They therefore conducted an open-label, prospective, phase 2 study (ClinicalTrials.gov Identifier: NCT04306965) to assess the potential benefit of combined treatment with dupilumab and apremilast among patients with moderate to severe atopic dermatitis.
Study investigators enrolled 10 patients with moderate to severe atopic dermatitis — as determined by an Investigator’s Global Assessment [IGA] score of 3 or greater after initiating treatment with dupilumab — that was not adequately controlled at study initiation (as indicated by an IGA ≥2).
Participants received apremilast 30 mg orally twice daily (after a 5-day titration period) added to dupilumab 300 mg administered via subcutaneous injection (9/10 patients received dupilumab every 2 weeks, and 1 patient received dupilumab weekly). The patients could continue their stable topical atopic dermatitis treatment and over-the-counter products. All patients were required to be receiving dupilumab for at least 12 weeks before enrollment in the study.
The primary endpoint was the proportion of patients who achieved an IGA score of 0 (clear) or 1 (almost clear) at week 16. In addition to the IGA, Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), itch as measured via the Numerical Rating Scale (NRS), and Eczema Area and Severity Index (EASI) assessments were also performed. The patients received an additional 8 weeks of combination treatment to evaluate the clinical benefit with continued use (ie, up to 24 weeks after initiation of apremilast).
The mean age of study participants was 42±21.7 years, and 80% were men. An intention-to-treat analysis was conducted with use of last observation carried forward and included all participants who received apremilast at week 0.
The primary endpoint of IGA 0 or 1 by week 16 was achieved by 2 participants; by 24 weeks, 3 patients had achieved IGA 0. Four patients achieved BSA ≤3% by week 16. BSA decreased by an average of 4.5±5.2% (mean±SD, 95% CI, 0.8-8.2), DLQI decreased by 3.9±3.1 points (95% CI, 1.7-6.1), pruritus as measured by the NRS decreased by 2.1±1.1 points (95% CI, 1.3-2.9), and EASI decreased by 3.02±2.8 (95% CI, 1.0-5.0).
By week 16, the participants were noted to have experienced a mean percentage change from baseline in BSA of -37.6±26.6% (95% CI, -56.7 to -18.6), in DLQI of -36.9±54.8% (95% CI, -76.3 to 2.3), in pruritus as measured by NRS of -45.9±17.8% (95% CI, -58.6 to -33.1), and in EASI of -32.6±42.6% (95% CI, -63.1 to -2.1). The study authors commented that when apremilast was evaluated as monotherapy for atopic dermatitis in the aforementioned study, the mean percentage change in EASI was -20.6%±40.1 (95% CI, -34.5 to 4.5).
Mild treatment-related adverse events — with nausea, diarrhea, and headache being the most common — were reported by 80% of the study participants. No serious adverse events were reported. The investigators report that 4 patients completed the study through week 16, with no discontinuations owing to lack of efficacy.
Study limitations include its open-label design, the small sample size, the high drop-out rate, and the use of other medications for atopic dermatitis.
“This study suggests that concomitant apremilast and dupilumab may be a promising combination for AD patients with an inadequate response to dupilumab,” the investigators concluded.
Disclosure: This study was financially supported by Celgene/Amgen. One of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Cunningham KN, Alsukait S, Cohen SR, et al. Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate-to-severe atopic dermatitis. J Eur Acad Dermatol Venereol. Published online January 23, 2023. doi:10.1111/jdv.18906