Oral roflumilast trims weight in patients with psoriasis

Treatment with oral roflumilast results in reduced body weight and appetite after 24 weeks in patients with psoriasis, a study has shown.

“With psoriasis being a chronic disease strongly linked to overweight and obesity, the current findings support the growing evidence of oral roflumilast as an alternative treatment in patients with moderate-to-severe plaque psoriasis,” the investigators said.

Post hoc analyses were performed on the PSORRO study, in which 46 patients with moderate-to-severe plaque psoriasis were randomly assigned 1:1 to receive either oral roflumilast 500 μg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups.

The investigators recorded the changes in body weight, blood pressure (BP), gastrointestinal symptoms, and laboratory tests. They did not apply any lifestyle or dietary interventions.

Baseline characteristics did not differ significantly between the treatment groups. Participants had a mean weight of 103.6 kg. [J Am Acad Dermatol 2024;91:64-71]

Patients who received oral roflumilast had a median weight loss of ‒2.6 percent at week 12 and ‒4 percent at week 24. For those treated with placebo, the corresponding weight changes were 0.0 percent and 1.3 percent. In addition, the roflumilast group had more frequent decrease in their appetite.

There were no changes seen in BP or laboratory tests.

Mechanism

The summary of product characteristics states that oral roflumilast therapy is associated with weight reduction. [www.ema.europa.eu/en/documents/product-information/daxas-epar-product-information_en.pdf]

Use of roflumilast, however, may be accompanied by gastrointestinal side effects such as diarrhoea, but patients experiencing this consequence may even have greater weight loss. [Lancet 2009;374:685-694]

“The mode of action is sparsely investigated, but some evidence point towards increased energy expenditure or glucagon-like peptide 1 (GLP-1)-mediated mechanisms, the latter supported by the observations of reduced appetite in the current trial,” the investigators said. [Diabetes Obes Metab 2017;19:496-508; Br J Pharmacol 2011;163:261-271; Diabetologia 2012;55:2779-2788]

GLP-1 is an incretin hormone secreted from enteroendocrine cells in response to food intake. It plays a major role in regulating satiety. GLP-1 analogs, therefore, may serve as a treatment option for obesity. [Mol Cell Endocrinol 2009;297:127-136]

“In the current trial, gastrointestinal symptoms, that is, nausea, abdominal pain, and/or diarrhoea, were reported in up to 39 percent of patients during the first 4 weeks after initiation of oral roflumilast, but thereafter diminished,” the investigators said.

“These findings support that the weight loss accompanying oral roflumilast therapy is driven by other factors than gastrointestinal side effects only,” they added.

In a 2009 study, patients with chronic obstructive pulmonary disease (COPD) treated with roflumilast lost an average of 2 kg of body weight at 1 year compared with placebo. [Lancet 2009;374:685-694]

“In contrast to COPD, where malnutrition and underweight are common and even a small weight loss may be critical, weight reduction is often favourable in patients with psoriasis,” the investigators said. [J Clin Diagn Res 2015;9:BC01-BC04; Eur Respir J 2002;20:539-544; Am J Clin Nutr 2005;82:53-59]

The current study was limited by its design and small sample size.