Phase 2 Randomized Trial Supports Roflumilast as a Potential Treatment for Seborrheic Dermatitis
1. Erythema, scaling, and itching caused by seborrheic dermatitis (SD) significantly decreased with roflumilast treatment.
2. Roflumilast treated for SD resulted in favourable local tolerability and safety profile.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Seborrheic dermatitis (SD) is a chronic dermatosis characterized by erythematous, scaly, and pruritic patches and plaques in areas of high sebaceous gland concentration. The patches and plaques often appear yellow, with dyspigmentation in patients with darker skin tones. First-line treatments include topical antifungals, corticosteroids, sulfur/sulfacetamide, and topical calcineurin inhibitors (off-label); however, they are all limited in their efficacy and/or safety. Therefore, this randomized control trial evaluated the safety profile and efficacy of 0.3% roflumilast foam, used once daily, in adult patients with scalp, face, and/or trunk SD. Roflumilast is a phosphodiesterase-4 inhibitor that can potentially suppress pro-inflammatory cytokines that contribute to SD. Currently, roflumilast is used to treat chronic obstructive pulmonary disease and is being investigated for other dermatological conditions such as atopic dermatitis, scalp psoriasis, and chronic plaque psoriasis. Of the 226 participants, roflumilast-treated patients had significantly higher rates of IGA success at week 2 and the end of treatment. Mean SD reductions were also significantly greater for the roflumilast-treated patients, and no serious adverse events occurred. Some limitations include the short treatment period (i.e., 8 weeks) and the small patient size.
Click to read the study in JAMA Dermatology
In-Depth [randomized control trial]: This phase 2, randomized parallel-group, double-blinded, vehicle-controlled clinical trial was conducted between November 12, 2019, and August 21, 2020, across 24 sites in the US and Canada. The safety and efficacy of 0.3% roflumilast foam in adult patients with SD on their scalp, face, and/or trunk were investigated. The primary objective was the Investigator Global Assessment (IGA) success. IGA success was defined by an IGA score of clear or almost clear plus 2-grade improvement from baseline at week 8. There were seven secondary objectives: (1) IGA success at weeks 2 and 4, (2) an erythema score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8, (3) a scaling score of 0 or 1 plus 2-grade improvement from baseline at weeks 2, 4, and 8, (4) a change in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline, (5) 4-point or greater WI-NRS score improvement in patients with a baseline WI-NRS score of 4 or greater, (6) safety profile, and (7) tolerability. Participant inclusion criteria included being 18 years or older, having a clinical diagnosis of SD for at least 3 months, and having an IGA score of 3 or greater, affecting 20% or less body surface area. SD areas included the scalp, face, trunk, and/or intertriginous areas. A requirement for participation in the study was the cessation of topical antifungals, corticosteroids, topical calcineurin inhibitors, sulfur-based treatments, medical devices, crisaborole, azelaic acid, and/or metronidazole use for two or more weeks before randomization. Rules for nonmedicated emollients, moisturizers, and sunscreens included once-daily use and application at least 3 hours after the study treatment to untreated areas only. The study included 4 phases: (1) screening (up to 4 weeks), (2) randomization, (3) 8-week treatment, and (4) 1-week follow-up. Patients were randomized to roflumilast or vehicle foam (2:1 ratio) using a computer-generated randomization list. The only difference between the vehicle foam and the roflumilast form was the absence of the active ingredient in the vehicle. Each participant received a blinded, unique number of kits (each had 2 blinded 60g of the assigned treatment) based on their body surface area involvement. Participants were instructed to apply the foam once daily, at least 20 minutes before bed. The exception to the application protocol was when the treatment was applied at the study site on day 0 and week 2. For scalp lesions, it was required for the scalp and hair to be dry before application. Furthermore, regardless of clearance, the treatment protocol was followed until the end of the 8 weeks. 328 patients were screened, and 226 were allocated to treatment groups (mean [SD] age, 44.9 [16.8] years; 116 men, 110 women). The roflumilast foam group comprised 154 participants, whereas the vehicle foam group comprised 72 participants. Of the 226, 208 participants (92.0%) completed the study. At baseline, more than 90% of participants had moderate severity of SD (IGA score = 3). IGA success was achieved in 104 (73.8%) roflumilast-treated patients and 27 (40.9%) vehicle-treated patients (P < .001). Furthermore, roflumilast-treated patients had significantly higher rates of IGA success at week 2 than vehicle-treated patients. WI-NRS mean SD reductions were 59.23% (52.5%) for the roflumilast-treated patients and 36.6% (42.2%) for the vehicle-treated patients (P < .001). Lastly, roflumilast and the vehicle foam were tolerated with similar rates of adverse events (e.g., contact dermatitis, insomnia, and nasopharyngitis). No serious adverse events were reported. At the end of the treatment phase, patients who met eligibility requirements were allowed to enroll in an open-label, single-arm, long-term trial, further evaluating the treatment safety. Overall, this randomized clinical trial demonstrated favourable efficacy, safety, and local tolerability for roflumilast SD treatment.
Image: PD
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