Oral Roflumilast Shows Promise for Moderate to Severe Psoriasis

Sixty-three percent of patients with moderate to severe psoriasis showed significant improvements in their psoriasis severity, and more than half experienced weight loss after treatment with oral roflumilast, according to one study.

Roflumilast demonstrates effectiveness and safety in treating psoriasis with added benefits for patients with comorbidities. | Image credit: Pawel - stock.adobe.com

This prospective cohort study is published in The Journal of Dermatological Treatment.

“Evidence from randomized controlled trials and real-world studies supports the efficacy of oral roflumilast in treating moderate to severe plaque psoriasis, scalp psoriasis, and palmoplantar psoriasis,” wrote the researchers of the study. “However, real-world evidence for oral roflumilast remains limited. This study aims to evaluate oral roflumilast in a real-world prospective cohort of patients with plaque psoriasis, focusing on clinical effectiveness and safety profile.”

Roflumilast was initially approved by the FDA in 2011 as oral treatment for patients with severe chronic obstructive pulmonary disease (COPD) with recurrent exacerbations.² In 2022, topical roflumilast 0.3% cream was FDA-approved for the treatment of plaque psoriasis in patients 12 years and older, marking it as the first topical PDE4 inhibitor for this condition. Building on its success, in 2023, the FDA also approved roflumilast 0.3% foam for the treatment of seborrheic dermatitis in patients 9 years and older, broadening its potential for managing various dermatologic conditions.

The study was conducted at a single center in Portugal between April 2023 and April 2024, involving adult patients with moderate to severe psoriasis who were treated with oral roflumilast 500 mcg once daily.¹ Disease severity was assessed using the Psoriasis Area and Severity Index (PASI), and effectiveness was measured through absolute PASI scores and changes from baseline. Additionally, a modified nonresponder imputation (mNRI) analysis was used to classify patients as nonresponders if they discontinued treatment due to lack of response, while an NRI intent-to-treat (NRI-ITT) analysis classified all patients who discontinued treatment as nonresponders.

Safety outcomes, including adverse events and reasons for discontinuation, were monitored throughout the study.

A total of 58 patients were included in the study. The baseline mean (SD) PASI score was 13.7 (5.5), and 72.8% of patients were classified as overweight or obese. By week 24, 63% of patients achieved PASI less than 5, 47.8% achieved PASI less than 3, and 21.7% achieved PASI less than 1. PASI75 and PASI90 response rates at week 24 were 67.4% and 45.7%, respectively.

PASI less than 5 was achieved in 50% of patients at week 24, with PASI75 and PASI90 rates of 53.4% and 36.2%. Throughout the study, 50% of patients discontinued treatment, primarily due to primary failure (24.1%), safety-related concerns (17.2%), or secondary failure (5.2%).

Mild gastrointestinal symptoms were common (44.8%), but no serious adverse events were reported. Notably, 53.4% of patients experienced weight loss, with an average reduction of 13.2 lb.

However, the researchers acknowledged some limitations. First, the study’s real-world design lacked the controlled conditions of randomized trials. It also had a small cohort size and a short follow-up period. Additionally, the study did not include direct comparisons with other oral psoriasis therapies, including alternative PDE4 inhibitors.

Despite these limitations, the researchers believe with its favorable safety profile and potential advantages over traditional treatments, roflumilast may become a valuable option for managing psoriasis, especially in those with comorbidities or limited access to biologic therapies.

“Roflumilast presents as a widely accessible, cost-effective, efficacious, and safe option for the treatment of plaque psoriasis,” the researchers wrote. “Its oral administration, favorable safety profile, and lack of required blood monitoring make it highly convenient for both patients and clinicians. Its efficacy and safety, comparable to that of apremilast, render it particularly useful for patients with mild to moderate psoriasis for whom topical therapies are no longer adequate.”

References

1. Lé AM, Yilmaz O, Luz M, Torres T. Oral roflumilast for psoriasis: a real-world 24-week prospective cohort study. J Dermatolog Treat. 2025;36(1):2464107. doi:10.1080/09546634.2025.2464107

2. Whittaker L. Roflumilast. DermNet. January 2023. Accessed February 13, 2025. https://dermnetnz.org/topics/roflumilast