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roflumilast, seborrheic dermatitis, phase 3 trial, tolerability
Introduction: Seborrheic dermatitis (SD) is a common, chronic, inflammatory dermatosis that affects patients of all ages with a global prevalence ≥5%. Treatments usually consist of topical therapies, including antifungals and low potency corticosteroids; however, current treatments have limitations such as side effects with long-term use and/or vehicles that can be difficult to use on both hair-bearing and non-hair-bearing areas. Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor once-daily foam under investigation for the treatment of SD. Efficacy, safety, and local tolerability of roflumilast foam 0.3% in patients with SD were demonstrated in a phase 2a and subsequent open-label trial (NCT04091646 and NCT04445987, respectively). Here, we present efficacy, safety, and local tolerability in a phase 3 trial of roflumilast foam 0.3% in patients with SD (NCT04973228).
Methods: This phase 3 randomized, parallel group, double blind, vehicle-controlled trial was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or non-scalp areas. Patients were randomized 2:1 to apply once-daily roflumilast foam 0.3% (n=304) or vehicle (n=153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) Success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included IGA score of Clear at Week 8, achievement of ≥4-point improvement from baseline in Worst Itch Numeric Rating Score (WI-NRS) among patients with baseline score ≥4 (WI-NRS Success), Overall Assessment of Erythema score of 0, and Overall Assessment of Scaling score of 0. Safety and local tolerability were also evaluated.
Results: Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved the primary efficacy endpoint of IGA Success (79.5% vs. 58.0%; P<0.0001) and IGA status of Clear (50.6% vs. 27.7%; P<0.0001) at Week 8. Percentages of patients achieving IGA Success and IGA Clear at Weeks 2 and 4 were also greater with roflumilast. Significantly greater percentages of roflumilast- than vehicle-treated patients achieved secondary endpoints of WI-NRS success at Weeks 2, 4, and 8 (62.8% vs. 40.6%; P<0.0001); Overall Assessment of Erythema score of 0 (57.8% vs. 32.0%; P<0.0001) at Week 8; and Overall Assessment of Scaling score of 0 (58.1% vs. 36.5%; P<0.0001) at Week 8. Local tolerability was favorable, with ≥98.9% of patients having no evidence of irritation at Weeks 4 and 8 on investigator-rated assessments and ≥92.3% of patients reporting a score of 0 (no sensation) or 1 (slight warm, tingling sensation; not really bothersome) after application on patient-rated tolerability. Overall incidence of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation were low, with similar rates between roflumilast and vehicle.
Conclusion: Once-daily roflumilast foam provided improvement across multiple efficacy endpoints vs vehicle while demonstrating favorable safety and tolerability in patients ≥9 years old with SD affecting scalp and/or non-scalp body areas.
Sponsored by Arcutis Biotherapeutics, Inc.
2. Dong C, et al. J PharmacolExp Ther. 2016;358:413–422.
3. ZirwasM, et al. 30th Congress of the European Academy of Dermatology and Venereology (EADV) Virtual, September 29–October 2, 2021.