AMSTERDAM – One in five psoriasis patients lost more than 5% of baseline body weight while on oral apremilast for 52 weeks in the phase III ESTEEM 1 and ESTEEM 2 trials.
Patients taking apremilast not only experienced marked improvement in their psoriasis, but also much-needed weight loss, Dr. Kristian Reich observed in presenting the ESTEEM trials analysis at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Kristian Reich
“You could see the weight loss in these studies as a side effect. But I think many of us would think that, in a psoriasis population with a mean baseline weight greater than 90 kg, that’s a very good thing to have,” said Dr. Reich of Dermatologikum Hamburg (Germany).
The mechanism for this weight loss remains unclear, Dr. Reich said. The important point is that it proved completely unrelated to the diarrhea, nausea, and vomiting that are common, albeit mild and transient, side effects associated with apremilast, a phosphodiesterase 4 inhibitor. That is, patients who lost significant weight did not have an increased incidence of these GI adverse events. Nor was there any correlation between baseline body weight and weight loss on the drug, he added.
Apremilast (Otezla) was approved by the Food and Drug Administration earlier in 2014 for the treatment of psoriatic arthritis, and in late September for psoriasis, and is the only systemic psoriasis drug that requires no tuberculosis screening or laboratory monitoring. The drug also is being developed as a medication for rheumatoid arthritis and ankylosing spondylitis.
The prospective ESTEEM I and II trials totaled 1,250 patients with moderate to severe psoriasis and a mean baseline weight of 92.6 kg. They were initially randomized 2:1 to 16 weeks of double-blind apremilast at 30 mg twice daily or placebo. At 16 weeks, everyone was placed on apremilast 30 mg b.i.d. through week 32, when a randomized treatment withdrawal phase began that lasted through week 52.
The weight loss associated with apremilast was progressive. Patients continued to lose weight while taking the drug until approximately week 65 of therapy, when weight loss has plateaued in long-term extension studies.
At 16 weeks in the ESTEEM trials, patients on apremilast had a mean 1.51-kg weight loss compared to baseline, while the mean body weight in placebo-treated controls remained unchanged. Also at week 16, 13.7% of the apremilast group and 5.5% of controls demonstrated a greater than 5% weight reduction from baseline.
The 564 patients on apremilast for the full 52 weeks had a mean weight loss from baseline of 1.99 kg, and 19.2% of patients had a weight loss in excess of 5%.
“I would call a 2-kg weight loss over a 1-year period a moderate weight loss. But a greater than 5% weight loss is generally classified by experts as clinically meaningful,” Dr. Reich noted.
While weight loss increased with time on apremilast, the drug’s GI side effects peaked during the first 2 weeks of therapy and tailed off after the first month.
Weight loss in apremilast-treated patients did not lead to any overt medical sequelae. Only 0.2% of patients discontinued the drug because of weight loss.
The ESTEEM analysis showed no sign of any increased risks of major adverse cardiovascular events, malignancies, serious infections, depressive symptoms, or suicidality in apremilast-treated patients, according to Dr. Reich.
“This is a drug known for having a very good safety profile,” he said.
The ESTEEM trials were funded by Celgene, which markets apremilast. Dr. Reich reported receiving research grants from and serving as a consultant to the company.