Alvin F. Wells, MD, PhD, Rheumatology and Immunotherapy Center, Franklin, Wisconsin, USA, reported results from the Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis (PsA) [PALACE4; NCT01307423]. Up to week 104, apremilast (APR) monotherapy produced clinically relevant improvements in the symptoms, physical function, and skin manifestations of PsA in patients who had not taken disease-modifying antirheumatic drugs (DMARDs).

PsA occurs in about 30% of patients with psoriasis and is prevalent in an estimated 0.3% to 1.0% of the general population [Gladman DD et al. Ann Rheum Dis. 2005]. The manifestations of PsA, including enthesitis, dactylitis, swollen and tender joints, and psoriasis, are associated with impaired physical function and health-related quality of life [Carneiro S et al. J Rheumatol. 2013; Sakkas LI et al. Semin Arthritis Rheum. 2013; Strand V et al. Health Qual Life Outcomes. 2013; Gladman DD et al. Ann Rheum Dis. 2005].

APR is an oral phosphodiesterase 4 inhibitor that regulates inflammatory mediators associated with the pathogenesis of PsA [Schafer PH et al. Br J Pharmacol. 2010]. PALACE4 was a phase 3, double-blind, randomized, placebo-controlled, parallel-group study designed to evaluate the long-term efficacy and safety of APR treatment compared with placebo over 104 weeks. The study consisted of 3 treatment phases with a planned overall study duration of up to 5 years.

To be eligible, patients were required to be DMARD-naïve adults with documented PsA with a duration ≥ 3 months and with ≥ 3 swollen joints and ≥ 3 tender joints. Patients with active tuberculosis or a history of incompletely treated tuberculosis, malignancy, or joint disease other than PsA were excluded. Participants were randomized (1:1:1) to receive placebo (n = 176), APR 20 mg BID (n = 175), or APR 30 mg BID (n = 176).

Efficacy assessments included the American College of Rheumatology 20%/50%/70% improvement response criteria (ACR20/50/70) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Safety assessments included adverse events (AEs) and clinical laboratory parameters at scheduled visits during each treatment phase (weeks 0, 4, 16, and 24 during the placebo-controlled phase; weeks 28, 40, and 52 during the blinded active treatment phase; and weeks 65, 78, 91, and 104 during the long-term open-label phase). There were no significant differences in baseline demographics and clinical characteristic among the groups.

At week 52, patients receiving APR 20 mg BID had ACR20/50/70 responses of 55.4%, 28.3%, and 12.0%, respectively. Patients receiving APR 30 mg BID had ACR20/50/70 responses of 58.0%, 29.8%, and 15.5%, respectively. The modified ACR20/50/70 responses were sustained through week 104.

Mean reductions from baseline in swollen tender joint count at week 104 for APR 20 mg and APR 30 mg were −8.7 and −9.5, respectively, and for tender joint count for APR 20 mg and APR 30 mg, −12.4 and −13.0, respectively. HAQ-DI scores improved for both doses of APR and at week 52 and week 104. The mean change from baseline to week 104 was −0.33 for APR 20 mg and −0.38 for APR 30 mg. The manifestations of PsA, including enthesitis, dactylitis, and psoriasis, were improved with both APR doses.

Most AEs were mild or moderate in severity in both APR doses and exposure periods. Diarrhea and nausea were the most often reported AEs. Discontinuations due to AEs were low. Marked laboratory abnormalities were similar in both APR and exposure periods, were generally infrequent, and returned to baseline with discontinued treatment. APR continued to demonstrate an acceptable safety profile and was generally well tolerated for up to week 104.