Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators. PALACE 4 compared the efficacy/safety of APR with placebo (PBO) in patients (pts) with active PsA who were DMARD-naïve.
Objectives Assess safety and tolerability of APR for up to 52 wks.
Methods Pts were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Pts with <20% reduction from baseline (BL) in SJC or TJC at Wk 16 were required to be re-randomized to APR20 or APR30 if initially randomized to PBO, or continued on their initial APR dose. At Wk 24, all remaining PBO pts were re-randomized to APR20 or APR30. The analysis reports data from the APR-exposure period (Wks 0 to 52).
Results 526 pts received PBO, APR20, or APR30 and were included in the safety population;. In the APR-exposure period, 252 pts received APR20 (192.8 pt-yrs) and 252 received APR30 (196.8 pt-yrs). Through Wk 52, AEs occurring in ≥5% of APR-exposed pts were nausea, diarrhea, headache, and URTI (Table). The nature, incidence, and severity of AEs were comparable over the 24-wk and 52-wk periods. Nearly 90% of AEs were mild/moderate in severity. Serious AEs (SAEs) occurred in 6.3% (APR20) and 2.4% (APR30) over 52 wks with no change in the type of SAEs reported between the 24-wk and 52-wk exposure periods. Through Wk 52, serious infections were reported by 1 pt receiving APR20 (chronic tonsillitis) and 2 pts receiving APR30 (gallbladder empyema; acute pyelonephritis); none were opportunistic infections. No deaths occurred. Discontinuation due to AEs in combined APR-exposed pts was 5.2% over 52 wks. No SAEs of diarrhea or nausea were reported. Most diarrhea and nausea events were generally reported within the first 2 wks of treatment and usually resolved in 4 wks without medical intervention. Discontinuation due to diarrhea and nausea was <2% in the combined APR group. Three cases of cancer were reported during the study: 2 cases of skin cancer (PBO, 1; APR30, 1) and 1 case of prostate cancer (APR20). The mean baseline BMI was 28.6 kg/m2 for the study population. Observed weight measurements were prospectively collected at selected study visits. At the end of the 52-wk APR-exposure period, the mean (median) weight loss was 0.91 kg (0.25 kg) in the APR20 and 1.19 kg (1.30 kg) in the APR30 group. Marked laboratory abnormalities generally were infrequent and returned to BL with continued treatment or were associated with a concurrent medical condition.
Conclusions APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks; the nature, incidence, and severity of AEs were comparable over the 24-wk and 52-wk periods. Similar to data from other phase 3 trials assessing pts previously treated with DMARDs, these data do not indicate a need for laboratory monitoring.
Disclosure of Interest A. Adebajo: None declared, A. Wells Grant/research support: Celgene Corporation, C. Edwards Grant/research support: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Consultant for: Celgene Corporation, Pfizer Inc, Roche, and Samsung, Speakers bureau: Abbott, Glaxo-SmithKline, Pfizer Inc, and Roche, A. Kivitz Grant/research support: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Consultant for: Amgen, Janssen, Eli Lilly, Novartis, Pfizer Inc, and UCB, Speakers bureau: Pfizer Inc, P. Bird Grant/research support: Celgene Corporation, K. Shah Employee of: Celgene Corporation, C. Hu Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, J. Aelion Grant/research support: Ardea, Astra Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer Inc, Roche, UCB Biosciences, Sanofi-Aventis, Takeda, Consultant for: Ardea, Astra Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Eli Lilly, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer Inc, Roche, UCB Biosciences, Sanofi-Aventis, Takeda, Speakers bureau: AbbVie, Amgen, and UCB