Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate‐to‐severe atopic dermatitis

Abstract

Apremilast 30 mg twice daily combined with dupilumab for the treatment of recalcitrant moderate-to-severe atopic dermatitis Dear Editor, The pathogenesis of atopic dermatitis (AD) is primarily due to overactive type 2 inflammation, 1 but the Th1 and Th17 pathways can also be activated in lesional skin. [2][3][4] Dupilumab, an interleukin (IL)-4 receptor alpha antagonist that blocks IL-4 and IL-13 cytokine signalling, is an FDAapproved treatment that has revolutionized the treatment of AD. 1 Nevertheless, many patients are still not fully controlled on dupilumab combined with topical therapy. Apremilast, an oral phosphodiesterase-4 inhibitor, is FDA approved for psoriasis, psoriatic arthritis and Behcet's disease. Apremilast can block multiple inflammatory mediators, including tumour necrosis factor-alpha, interferon-gamma, IL-2, IL-12, IL-13 and IL-17. 5,6 While apremilast monotherapy in AD was unsuccessful at significantly improving patients at the FDAapproved dose of 30 milligrams (mg) twice daily, a trend toward Eczema Area and Severity Index (EASI) improvement was observed at Week 12. 6 Therefore, we investigated whether apremilast used in combination with dupilumab would give added benefit to patients.This IRB-approved, open-label, prospective phase 2 study evaluated apremilast 30 mg orally twice daily (after 5-day titration) when added to dupilumab 300 mg b for 10 patients with moderate-to-severe AD, classified as an Investigator's Global Assessment (IGA) score of 3 or greater upon beginning dupilumab, that was not adequately controlled at study initiation (IGA 2 or greater). Patients were permitted to continue their current stable topical AD prescription and over-the-counter regimens and had to be on dupilumab for a minimum of 12 weeks prior to enrolment. b The primary endpoint was the proportion of patients who after starting apremilast, achieved an IGA score of 0 (clear) or 1 (almost clear) at Week 16. Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), itch on Numerical Rating Scale (NRS) and EASI were also recorded. An additional 8 weeks of study drug was administered to assess clinical benefit with continued use, up to 24 weeks after the introduction of apremilast.Patient demographics, clinical characteristics and efficacy outcomes are summarized in Table 1. An intention-to-treat analysis was performed using last-observation-carriedforward and included all enrolled patients who received apremilast at Week 0. Two patients reached the primary endpoint of IGA 0 or 1 by Week 16, and by 24 weeks, this increased to 3 patients. At 16 weeks, BSA ≤3% was achieved in 4/10 patients. BSA, DLQI, NRS pruritus and EASI decreased by an average of 4.5 ± 5.2% (mean ± standard deviation, 95% confidence interval [CI] 0.8-8.2), 3.9 ± 3.1 points (95% CI 1.7-6.1), 2.1 ± 1.1 points (95% CI 1.3-2.9) and 3.02 ± 2.8 (95% CI 1.0-5.0), respectively. Mean percent change from baseline BSA, DLQI, NRS pruritus and EASI was −37.6 ± 26.6% (95% CI -56.7 to −18.6), −36.9 ± 54.8% (95% CI -76.3 to 2.3), −45.9 ± 17.8% (95% CI -5...