Initial results from the PALACE--1 trial show that the oral phosphodiesterase-4 inhibitor apremilast safely and effectively relieves symptoms of psoriatic arthritis.
Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al., Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis (2014) Published online first 4 March 2014. doi:10.1136/annrheumdis-2013-205056.
Some of the results for a drug with a new mechanism against psoriatic arthritis (PsA), originally reported at last fall's American College of Rheumatology annual meeting, are now available online in full text. The oral phosphodiesterase-4 inhibitor apremilast safely and effectively improves signs, symptoms, and the physical functioning of patients with active psoriatic arthritis (PsA), according to the first of four phase 3 clinical trials.
The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) trial compared apremilast with placebo in 504 patients whose PsA remained active despite treatment with a traditional disease-modifying antirheumatic drug (DMARD) and/or a biologic therapy.
In the initial 24-week, placebo-controlled phase of the PALACE 1 trial, conducted in 13 countries, patients were first randomized to placebo, apremilast 20â mg twice a day (BID), or twice-daily doses of 30â mg. Most patients were white women under age 65.
After 16 weeks, patients in the placebo or the lower-dose groups who did not achieve a reduction of 20% in the American College of Rheumatology response criteria (ACR20) were re-randomized to apremilast 20 mg or 30 mg. At 24 weeks all patients were re-randomized to either dose of apremilast.
Those patients who were taking concurrent DMARDs -- methotrexate, leflunomide, and/or sulfasalazine -- continued on stable doses of those drugs.
At week 16, 40% of the 30 mg apremilast group reached ACR20 criteria, a highly significant difference (p=0.0001) from results for those on the 20â mg BID dose (31%) or placebo (19%) -- although the effect of the lower dose was itself significantly better (p=0.016) than placebo.
Although the study was not designed to make dose comparisons for secondary outcomes, it appeared that high-dose PALACE 1 patients showed significantly greater and more consistent responses in measures such as physical function and skin psoriasis compared to those on placebo.
Apremilast was generally well-tolerated over 24 weeks and had an acceptable safety profile, with the most common adverse events being early, self-limiting gastrointestinal episodes, which only infrequently led to discontinuation.
There were no differences between the groups in major adverse cardiac events, serious or opportunistic infections, malignancies, or laboratory abnormalities. The safety phase is continuing to 52 weeks and the open-label phase to five years.