Roflumilast serves up weight-loss benefit for patients with psoriasis

In the treatment of patients with psoriasis, the phosphodiesterase (PDE)-4 inhibitor roflumilast has been found to also induce weight loss.

In the randomized PSORRO trial, one in three patients achieved at least 5-percent weight loss—the scale that endocrinologists consider to be clinically meaningful—with 12 weeks of oral roflumilast therapy, reported senior investigator Dr Alexander Egeberg of Gentofte Hospitalsvej in Hellerup, Denmark.

“Importantly, no patients became underweight during the study,” Egeberg added.

A total of 46 adult patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥8) were included in the trial. The inclusion and exclusion criteria, according to Egeberg, were fairly standard, with a few exceptions. For example, the PASI scores were slightly low, although this should not affect the results, since the study only looked at the cardiometabolic parameters. Also, none of the patients were underweight at baseline.

Half of the patients received roflumilast 500 μg (median age 38 years, 65 percent men, mean body weight 102.0 kg) and half received placebo (median age 39 years, 83 percent men, mean body weight was 105.1 kg). Treatment was administered once a day for 12 weeks. This was followed by active, open-label treatment with roflumilast in both groups through week 24. A total of 13 percent and 9 percent of patients in the roflumilast and placebo group, respectively, had type 2 diabetes. None received bariatric surgery or body weight-lowering medications before or during the study.

Over 12 weeks, the roflumilast group showed a rapid reduction in body weight, with weight loss continuing through week 24. The median weight change was significantly bigger for patients who received roflumilast throughout than for those who initially received placebo (weeks 12: –2.6 percent vs 0.0 percent; week 24: –4 percent vs –1.3 percent). [EADV 2023, abstract 6626]

In the roflumilast group specifically, 57 percent, 30 percent, 17 percent, and 13 percent of patients lost ≥3 percent, ≥5 percent, ≥10 percent, and ≥15 percent, respectively, of their baseline body weight during the 24-week study.

Of note, baseline weight correlated with weight change at week 12. Egeberg highlighted that the higher the weight of the patients at baseline, the greater the weight-loss benefit obtained with roflumilast. Some patients went from a higher weight status to a lower weight status (eg, from obese class 3 to obese class 2 or from overweight to normal weight). There were no reports of patients becoming underweight, suggesting that roflumilast is safe to use in patients with normal weight, Egeberg explained.  

Reduced appetite was the most pronounced adverse event in patients taking roflumilast, which Egeberg said may explain why the patients lost weight. Patients started experiencing loss of appetite early on, and this adverse event persisted later in the study. Meanwhile, other gastrointestinal adverse events such as nausea, abdominal pain, and diarrhoea were marked early on but decreased to placebo levels quickly. There were no changes in blood pressure or laboratory tests observed.

“With low costs, oral administration, favourable safety profile, and proven efficacy in psoriasis, roflumilast may be an attractive therapy, especially in overweight or obese patients,” Egeberg said of the findings of PSORRO.

When asked whether roflumilast could be used for weight loss in individuals without psoriasis, given the cost of the medication, Egeberg noted that new GLP-1 analogues have a much more impressive weight-loss effect.

“I don’t think [roflumilast] will ever outcompete [those GLP-1 analogues]. But for patients with psoriasis and other diseases, such as hidradenitis suppurativa, roflumilast is a good alternative if the patients want to [lose] weight,” he said.