What is Roflumilast (Daxas) indicated for on the skin?

Roflumilast in Dermatology: Topical Applications for Skin Conditions

Roflumilast is FDA-approved as a topical 0.3% cream for the treatment of plaque psoriasis and seborrheic dermatitis in patients 12 years and older. It is not indicated for oral use in dermatological conditions.

Mechanism of Action and Formulation

Roflumilast is a phosphodiesterase-4 (PDE4) inhibitor that works by:

• Inhibiting PDE4 enzyme, leading to accumulation of cyclic adenosine monophosphate (cAMP)
• Suppressing inflammatory mediators including interferon-γ and tumor necrosis factor-α 1
• Providing potent anti-inflammatory effects in the skin with minimal systemic exposure

The topical formulation (0.3% cream) is designed for once-daily application and demonstrates:

• High skin concentrations (61.8-126 fold higher than plasma levels) 2
• Low systemic bioavailability of approximately 1.5% 2
• Steady state reached by day 15 with a half-life of approximately 4 days 2, 1

FDA-Approved Dermatological Indications

1. Plaque Psoriasis

   • Approved for patients 12 years and older
   • Particularly effective for treating sensitive areas including intertriginous regions 1
   • Clinical trials (DERMIS-1 and DERMIS-2) showed Investigator Global Assessment success rates of 42.4% and 37.5% with roflumilast 0.3% cream compared to 6.1% and 6.9% with vehicle 1

2. Seborrheic Dermatitis

   • Approved for mild to moderate cases 3
   • Once-daily application

Emerging Evidence for Other Dermatological Uses

Recent research suggests potential off-label uses for roflumilast in:

• Atopic dermatitis 4
• Nummular eczema (case reports) 3
• Lichen planus (case reports) 3

Safety Profile and Adverse Effects

Topical roflumilast has a favorable safety profile:

• Low discontinuation rate (1%) in clinical trials 1
• Most common adverse reaction leading to discontinuation was urticaria at application site (0.3%) 1
• No significant reports of diarrhea, headache, or insomnia with topical application 2
• Significantly fewer systemic side effects compared to oral PDE4 inhibitors

Advantages Over Other Topical Treatments

• Effective in treating sensitive areas including skin folds where corticosteroids may be problematic 1
• Once-daily application improves adherence
• No tachyphylaxis or skin atrophy concerns that are associated with topical corticosteroids
• More potent PDE4 inhibition than crisaborole (another topical PDE4 inhibitor), with in vitro IC50 of 0.7 nM for roflumilast versus 0.24 μM for crisaborole 4

Important Considerations

• While oral roflumilast is approved for COPD management, its oral formulation is not FDA-approved for dermatological conditions
• A recent randomized controlled trial (PSORRO) did evaluate oral roflumilast for moderate-to-severe psoriasis, showing 35% of patients achieved PASI75 at week 12 versus 0% with placebo 5, but this remains an off-label use
• Topical application should be prioritized for dermatological conditions to minimize systemic exposure and side effects

Roflumilast represents an important non-steroidal topical option for inflammatory skin conditions, particularly for sensitive areas where corticosteroids may be contraindicated or problematic.