Commentary: Efficacy and Safety of Oral Roflumilast for Moderate to Severe Psoriasis—A Randomized Controlled Trial (PSORRO)

Roflumilast is a targeted phosphodiesterase (PDE)-4 inhibitor that reduces pro-inflammatory cytokines. Oral roflumilast was approved for treating severe COPD over a decade ago, and generic, low-cost versions are available in many countries. The present study evaluates the efficacy and safety of oral roflumilast in treating patients with moderate to severe plaque psoriasis. It is a company-independent, multicenter, randomized, double-blind, placebo-controlled trial conducted at three major Danish university hospitals between January 1, 2021, and December 12, 2022. Patients included had to be ≥18 years old, had chronic stable plaque psoriasis, PASI ≥8, a body mass index (BMI) ≥20 kg/m2, and should have an indication for systemic treatment. Concomitant topical treatments were not allowed except in case of significant flare-ups, where topical steroids or calcineurin inhibitors could be prescribed.

After randomization, patients were assigned by site investigators to monotherapy with either placebo or oral roflumilast 500 μg once daily for 12 weeks. All patients received open-label treatment from week 12 to 24 with oral roflumilast 500 μg once daily. The study enrolled 46 patients, of which 42 patients completed week 12 and 38 patients the week 24 visit. In roflumilast and placebo groups, the median PASI at randomization was 10.9 and 10.6.

At week 12, the efficacy primary endpoint evaluation, PASI75 was achieved by 8 (35%) patients in the roflumilast group compared to 0 (0%) patients in the placebo group (p = 0.014), and PASI50 was achieved by 70% of patients in the roflumilast group vs 4% in the placebo. During the open-label period (weeks 12 to 24), PASI75 and PASI50 were achieved in 39% and 57% of patients initially assigned to a placebo. In patients assigned to roflumilast from week 0, 44% and 65% achieved PASI75 and PASI50, respectively, and 22% achieved PASI90. There were no serious adverse events in either group or significant biochemical changes during the trial period. The most common side effects were gastrointestinal symptoms, like diarrhea, náusea, and abdominal pain.

Psoriasis has many treatment options today, but innovative oral medications with low costs are still lacking. Methotrexate is usually the only option for systemic treatment in low-income countries, despite the low rate of PASI75 responses, contraindications, and frequent side effects. Although this was not a head-to-head study, roflumilast appears to have a similar or better efficacy profile than apremilast, another approved PDE4 inhibitor. About 30% of patients reach PASI75 responses on apremilast, and gastrointestinal symptoms may be encountered more frequently.

The present study is interesting since it raises the following considerations:

1. Oral roflumilast might help treat psoriasis and comorbidities such as COPD, obesity, and type 2 diabetes.
2. The drug appears to be a safe and inexpensive oral option that could be used in combination with other drugs.

The study’s main limitation is that this was a small phase 2 study, with an overrepresentation of male patients. The study was only 24 weeks, so longer-term outcomes with oral roflumilast are still unclear. Nevertheless, since the drug has been approved for COPD for over a decade, extensive safety data are available from non-psoriasis populations. With the convenience of once-daily oral treatment, roflumilast may be an inexpensive alternative to other systemic treatments in patients lacking access to effective psoriasis therapies.