Oral Apremilast Showing Promise in Psoriatic Arthritis

Alice Goodman

June 13, 2013

MADRID, Spain —The investigational oral drug apremilast (Celgene Corporation) continues to demonstrate meaningful clinical improvement in the signs and symptoms of psoriatic arthritis, physical function, and skin improvement at 52 weeks, according to updated results from the PALACE-1 trial.

Up to 65% of patients with active psoriatic arthritis despite treatment achieved at least a 20% improvement at the end of the study.

"Durability of response is important to patients with psoriatic arthritis," said lead investigator Arthur Kavanaugh, MD, from the University of California at San Diego. "This relatively large study shows that apremilast maintains its efficacy and safety for over a year in patients previously treated with disease-modifying anti-rheumatic drugs [DMARDs] and biologic agents," he said.

"The results suggest that apremilast will become a therapeutic option for psoriatic arthritis patients," said Dr. Kavanaugh. "The longer the data we have, the better."

Apremilast is an inhibitor of phosphodiesterase-4 that modulates a network of pro- and anti-inflammatory intracellular mediators.

Dr. Kavanaugh noted that because very few laboratory abnormalities were seen over the 52 weeks, patients taking apremilast might not need to be monitored as often as with anti-tumor necrosis factor inhibitors.

PALACE-1, part of a large development program for apremilast, is a phase 3, multicenter, double-blind, placebo-controlled, parallel-group study that enrolled 504 patients with active psoriatic arthritis despite treatment with DMARDs and biologics.

Investigators randomized patients to apremilast 20 mg or 30 mg twice daily or placebo for 24 weeks. At week 16, patients were permitted early escape if their disease was uncontrolled. At week 24, patients in the placebo group were rerandomized to one of the apremilast groups.

At baseline, all patients had psoriatic arthritis for more than 6 months and had failed on previous therapy. If they were taking a DMARD, they could remain on it for the duration of the trial. In all, 76% of patients were biologic-naïve, and more than two thirds were taking nonsteroidal anti-inflammatory drugs. A total of 48% had more than 3% of their body surface covered with psoriatic plaques.

Week 16 data, presented in 2012 and reported at the time by Medscape Medical News, showed that apremilast was superior to placebo in meeting American College of Rheumatology 20 (ACR20) criteria.

At week 16, the ARC20 end point was achieved by more patients in the 20 mg group than in the placebo group (31.3% vs 19.4%; P =.014); the same was true for the 30 mg group (40.0% vs 19.4%; < .0001).

The rate was higher at 52 weeks.

Table. Patients Meeting ACR20 Criteria at 52 Weeks

Apremilast Percent
20 mg 63.0
30 mg 54.8


Dr. Kavanaugh reported that about 10% to 20% of patients had even better responses.

Patients treated with apremilast had clinically meaningful improvements in baseline function, as indicated by a decrement of 0.35 on the Health Assessment Questionnaire Disability Index (HAQ-DI).

Of the 48% of patients with the involvement of more than 3% body surface area at baseline, a 75% improvement on the Psoriasis Skin Index (PASI-75) was achieved by 37% of patients in the 30 mg group and by 25% in the 20 mg group.

"These results show that the skin can be improved with this therapy," Dr. Kavanaugh said.

Adverse Events

Apremilast had a good safety profile at week 24 and at week 52. The incidence of adverse events was low and comparable between groups, with no observed malignancy or opportunistic infection. Gastrointestinal toxicity was the most common adverse event. No new severe diarrhea or nausea was seen after 6 months of treatment, and no patients withdrew after 6 months because of this adverse effect.

At week 16, the incidence of laboratory abnormalities was quite low and similar between the placebo and apremilast groups; it remained low at 52 weeks.

"Success breeds success. We are very happy with these data," Dr. Kavanaugh said. "We still need to see where its role will be. Perhaps it will be useful for patients who are not refractory to other treatments."

Ulf Müller-Ladner, MD, from the University of Giessen in Germany, who was asked by Medscape Medical News to comment on the findings, explained that "an oral drug is quite convenient for patients. We don't have as many good options for treating psoriatic arthritis as we do for rheumatoid arthritis, so any new drug that is approved will be used."

"The studies include patients who are not that sick. In real life, patients are sicker and have organ involvement and more comorbidities. The signals from the studies thus far are that apremilast could be useful in real-life circumstances," Dr. Müller-Ladner noted.

This study was funded by Celgene. Dr. Kavanaugh reports receiving grant and research support from the company and from Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Centocor-Janssen, Pfizer, Roche, and UCB. Dr. Müller-Ladner reports receiving consultant and research grants from every company that makes biologics for the treatment of rheumatic diseases.

European League Against Rheumatism (EULAR) Congress 2013: Abstract LB0001. Presented June 12, 2013.


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