Oral roflumilast treatment may induce weight loss in patients with psoriasis

Key takeaways:

• After 12 weeks of treatment, 35% of patients lost 5% or more of their baseline bodyweight.
• By week 12, the roflumilast group saw a mean weight reduction of 2.6%, whereas the placebo group saw none.

Treating psoriasis with oral roflumilast may induce weight loss, positioning the drug as a potentially attractive alternative for patients with psoriasis, according to a study.

Approved in 2011 for the treatment of severe chronic obstructive pulmonary disease (COPD), oral roflumilast is a phosphodiesterase-4 inhibitor that frequently exhibits a side effect of weight loss — an outcome that may be appealing to patients who suffer from psoriasis and the condition’s accompanying comorbidity of obesity.

“Psoriasis is a common inflammatory skin disease associated with a range of cardiometabolic comorbidities, including obesity,” Mette Gyldenløve, MD, PhD, associate professor in the department of dermatology and allergy at Herlev and Gentofte Hospital at University of Copenhagen, and colleagues wrote. “Obese patients with psoriasis respond less well to systemic psoriasis therapy, and weight loss reduces psoriasis severity.”

Researchers have conducted a post-hoc analysis from the PSORRO study, in which oral roflumilast was evaluated for the treatment of patients with moderate to severe plaque psoriasis, to assess the effects of the drug on body weight and cardiometabolic parameters in these patients.

In PSORRO, 46 patients were randomly assigned 1:1 to receive roflumilast 500 g (the in-label dosage for COPD) or placebo once daily for 12 weeks, followed by an additional 12 weeks where all patients received roflumilast. Of the 46 patients, 42 completed treatment through week 12 and 38 remained through week 24.

In the treatment and placebo arms, mean body weight was 102 kg and 105.1 kg, respectively. Additionally, 13% and 9% of participants also had type 2 diabetes.

By week 12, patients treated with roflumilast saw a mean weight reduction of 2.6% (interquartile range [IQR], –6.3% to –0.7%) from baseline, whereas the placebo group saw no reduction at all.

Through week 24, the roflumilast group continued to lose weight, landing at a mean weight reduction of 4% (IQR, –7.8% to –2%) from baseline to the end of the study. Those that switched from placebo to roflumilast at week 12 saw a mean weight reduction of 1.3% (IQR, –3.4% to –0.3%) by week 24.

“After 12 weeks, a total of 35% of patients treated with roflumilast had lost 5% or more of their baseline bodyweight, which is widely accepted as a clinically meaningful change, compared with 0% in the placebo group,” the researchers wrote. “No patients became underweight during the study.”

Reduced appetite was also reported by more patients in the roflumilast vs. placebo group. However, significance was only observed at week 4 (61% vs. 26%; P = .02). These numbers leveled out by week 24 and no statistical significance was found between treatment arms in terms of decreased appetite.

In addition to reduced appetite, nausea, abdominal pain and diarrhea were present during the first 4 weeks of treatment in up to 39% of patients; however, they diminished with time.

“These findings support that the weight loss accompanying oral roflumilast therapy is driven by other factors than gastrointestinal side effects only,” the authors explained. “With psoriasis being a chronic disease, strongly linked to overweight and obesity, the current findings support the growing evidence of oral roflumilast as a treatment alternative in patients with moderate to severe plaque psoriasis.”

Reference:

• Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022522s003lbl.pdf. Updated August 2013. Accessed March 27, 2024.