Background Apremilast (APR), an oral phosphodiesterase 4 inhibitor, regulates immune activity in psoriatic arthritis (PsA) patients. Safety data were pooled from the phase 3 PALACE 1, 2, and 3 studies.
Objectives Evaluate the long-term safety of APR treatment for up to 4 years in patients with active PsA despite prior conventional DMARDs and/or biologics.
Methods Patients were randomized at baseline (1:1:1) to placebo (PBO), APR 30 mg BID (APR30), or APR 20 mg BID (APR20). PBO patients were re-randomized to APR30 or APR20 at Week 16 (early escape) or Week 24. Double-blind APR treatment continued to Week 52; patients could continue APR during an open-label, long-term treatment phase for up to 5 years treatment. Visits in years 2, 3, and 4 were scheduled at 13-week intervals. Safety was assessed at each visit throughout the study, and results are summarized here by exposure.
Results A total of 1493 patients were randomized and received ≥1 dose of study medication (PBO: n=495; APR30: n=497; APR20: n=501). At the 4-year data cut, the numbers of patients receiving APR30 and APR20 in each exposure period were 1441 in Weeks 0 to ≤52, 1028 in Weeks >52 to ≤104, 865 in Weeks >104 to ≤156, and 767 in Weeks >156 to ≤208. During the 0- to ≤52-week APR-exposure period, adverse events (AEs) occurring in ≥5% of APR30-exposed patients were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis (Table). Most diarrhea and nausea AEs were reported within the first 2 weeks of treatment and usually resolved within 4 weeks; the frequency of gastrointestinal AEs decreased with longer APR30 exposure, and the frequency of other common AEs either decreased or remained stable with prolonged exposure (Table). Most AEs were mild/moderate in severity. During Weeks >156 to ≤208 of APR exposure, the discontinuation rate due to AEs was 1.7% with APR30, and the rate of serious AEs (SAEs) was 7.0%, consistent with earlier periods; most SAEs occurred in 1 patient each. Rates were very low for major cardiac events, malignant neoplasms, and serious opportunistic infections, comparable to the first year of treatment. Rates of depression remained very low in Weeks >156 to ≤208. Marked laboratory abnormalities were infrequent, and most returned to baseline with continued treatment.
Conclusions APR30 demonstrated a favorable safety profile and was well tolerated for up to 208 weeks, marked by the lack of accumulation of immunosuppression or need for specific laboratory monitoring. The incidence of AEs remained stable or decreased with long-term exposure to APR30.
Disclosure of Interest P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Genentech, Janssen, Eli Lilly, Novartis, Pfizer, Roche, UCB, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Genentech, Janssen, Eli Lilly, Pfizer, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, J. Gomez-Reino Grant/research support from: Roche and Schering-Plough, Consultant for: BMS, Pfizer, Roche, Schering-Plough, UCB, S. Hall Consultant for: Boehringer Ingelheim, MSD, Roche, Schering-Plough, Servier, Wyeth, Paid instructor for: Amgen, AstraZeneca, Boehringer Ingelheim, Centocor, GSK, MSD, Pfizer, Sanofi Aventis, Sanofi Pasteur, Schering-Plough, Serono, Wyeth, Speakers bureau: Boehringer Ingelheim, GSK, MSD, Pfizer, Roche, Sanofi Aventis, Schering-Plough, Wyeth, A. Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, E. Lespessailles Grant/research support from: Amgen, Eli Lilly, Novartis, Servier, Speakers bureau: Amgen, Eli Lilly, Novartis, Servier, G. Schett Grant/research support from: Abbott, Celgene Corporation, Roche, UCB, Consultant for: Abbott, Celgene Corporation, Roche, UCB, M. Paris Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, J. Wollenhaupt Grant/research support from: Abbott, BMS, MSD, Pfizer, UCB, Consultant for: Abbott, BMS, MSD, Pfizer, UCB