Topical Roflumilast 0.3% Effective, Safe in Systematic Review of Psoriasis Data

Treatment of psoriasis with topical roflumilast 0.3% is an effective and safe option for patients, with new data showing the drug outperforms vehicle across clinician- and patient-reported outcomes.1

Bibek Shrestha, MBBS, from Tribhuvan University Institute of Medicine in Nepal, led a team of other investigators in authoring the systematic review and meta-analysis leading to these findings. The investigators highlighted the promise of roflumilast, a selective phosphodiesterase-4 (PDE-4) inhibitor, as a therapeutic agent addressing concerns over cutaneous inflammation.2

“While individual randomized trials have demonstrated clinical improvement with topical roflumilast, there is no systematic review that summarizes evidence on efficacy and safety in patients…” Shrestha et al wrote.1 “Thus, we performed this systematic review and meta-analysis to evaluate the efficacy and safety of topical roflumilast 0.3% in patients with plaque psoriasis.”

Design and Findings on Topical Roflumilast

The investigative team systematically searched, from their inception through May 2025, the Embase, Cochrane CENTRAL, ClinicalTrials.gov, and PubMed databases. They had sought to identify eligible RCTs for their analysis. Two independent reviewers were asked to screen all RCT titles and abstracts. They would determine which research fulfilled predetermined criteria for full-text evaluation. Any notable disagreements were resolved by the team through consultation with a third reviewer.

In their analysis, Shrestha and coauthors focused on several clinical endpoints in these RCTs, including Investigator’s Global Assessment (IGA) or body-IGA success, which was defined as attainment of clear or almost clear skin with a minimum 2-grade improvement from baseline. They also looked at data related to Psoriasis Area and Severity Index thresholds (PASI-50, PASI-75, PASI-90), to scalp-IGA (S-IGA), to intertriginous-IGA (I-IGA), and to PSSI-75, a score suggesting a 75% Psoriasis Scalp Severity Index improvement.

Additional outcomes highlighted by the investigative team included Numeric Rating Scale (WI-NRS) success attainment, Worst Itch, 8-week Psoriasis Symptoms Diary (PSD) scores, and reported occurrences of adverse events (AEs). The team's statistical calculations were done via Review Manager. They measured heterogeneity across RCTs with the Higgins I² statistic.

Across a set of 5 RCTs, involving 1835 study participants, Shrestha et al pointed to results suggesting topical roflumilast 0.3% led to significant increases in the rates of IGA/body-IGA improvement at the 8-week mark (RR 4.19; 95% CI 2.49–7.04; P < .00001).1 They also noted substantial increases in S-IGA success (RR 3.37; 95% CI 1.57–7.25; P = .002) as well as I-IGA success (RR 3.32; 95% CI 2.11–5.22; P < .00001).

Superior outcomes resulting from treatment with roflumilast were observed in PASI-50, PASI-75, PASI-90, and PSSI-75 scores.1 Relative risks were shown by the investigators to range from 2.55 to 4.32 (all P < .00001). PSD score improvements (MD –25.34; 95% CI –31.77 to –18.92) and WI-NRS improvements (RR 2.12; 95% CI 1.74–2.60) were likewise found to be significant. AEs were identified more frequently among individuals being treated with topical roflumilast (RR 1.29; 95% CI 1.08–1.54; P = .004).

While Shrestha and colleagues' findings in this systematic review and meta-analysis provide strong evidence suggesting topical roflumilast 0.3% psoriatic signs and symptoms improvements compared with vehicle, additional research was described as necessary to fill remaining gaps in the data. Future assessments were highlighted as needed to prioritize direct comparisons between roflumilast and other established topical drugs, with the aim being more clearly defining any distinctions in efficacy and safety across various psoriasis therapies.

“Combined with the favorable tolerability profile of topical 0.3% roflumilast, these key findings highlight topical roflumilast's potential to effectively and safely address the therapeutic needs of psoriasis patients,” Shrestha and coauthors concluded.1

References

1. AA Khattak, A Javed, UA Rahman, et al. Clinical Efficacy and Safety of Topical Roflumilast in Psoriasis: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. JEADV Clinical Practice 0 (2025): 1-13, https://doi.org/10.1002/jvc2.70253.

2. Hatzelmann A, Morcillo EJ, Tenor H, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2010 Aug;23(4):235-56. doi: 10.1016/j.pupt.2010.03.011. Epub 2010 Apr 7. PMID: 20381629.