FRI0470 Long-Term (156-Week) Safety Profile of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Pooled Safety Analysis of 3 Phase III, Randomized, Controlled Trials
Authors: P.J. Mease, D.D. Gladman, J.J. Gomez-Reino, S. Hall, A. Kavanaugh, E. Lespessailles, G. Schett, K. Shah, L. Teng, J. Wollenhaupt
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Apremilast (APR), a phosphodiesterase 4 inhibitor, acts to regulate immune activity in psoriatic arthritis (PsA) patients. PALACE 1 (NCT01172938), 2 (NCT01212757), and 3 (NCT01212770) compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA despite prior conventional DMARDs and/or biologics. <h3>Objectives</h3> Assess the long-term safety of APR treatment for patients treated for up to 3 years with APR. <h3>Methods</h3> Patients were randomized (1:1:1) to PBO, APR 30 mg BID (APR30), or APR 20 mg BID (APR20) stratified by baseline DMARD use (yes/no). The PBO-controlled phase continued to Week 24; 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 to receive APR during an open-label, long-term treatment phase. Visits in years 2 and 3 were scheduled at 13-week intervals. <h3>Results</h3> 1493 patients were randomized and received ≥1 dose of study medication (PBO: n=495; APR30: n=497; APR20: n=501). At the studies9 3-year data cut, a total of 1441 (1209.3 patient-years), 1028 (937.8 patient-years), and 865 (790.4 patient-years) patients received APR in the Weeks 0 to ≤52, Weeks &gt;52 to ≤104, and Weeks &gt;104 to ≤156 periods, respectively, relative to the start of APR. During the Weeks 0 to ≤52 APR-exposure period, adverse events (AEs) occurring in ≥5% of APR-exposed patients were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis (Table). Most diarrhea and nausea events were reported within the first 2 weeks of treatment and usually resolved in 4 weeks without medical intervention. The frequency of gastrointestinal AEs decreased with longer exposure (i.e., Weeks &gt;52 to ≤104 or &gt;104 to ≤156; Table); occurrence &gt;5% of other common AEs either decreased in frequency or remained stable with prolonged exposure (Table). Most AEs were mild or moderate in severity up to 156 weeks of APR-exposure. Rates of depression remained very low, consistent with earlier findings. The rate of serious AEs (SAEs) was 8.1% during Weeks &gt;104 to ≤156 of APR exposure; most SAEs occurred in 1 patient each. For SAEs of special interest (major cardiac events, malignant neoplasm, opportunistic infection), rates were very low and comparable to those in the first year of treatment. Discontinuation due to AEs was 1.6% during Weeks &gt;104 to ≤156 of APR exposure. Marked laboratory abnormalities were infrequent, and most returned to baseline with continued treatment. <h3>Conclusions</h3> APR demonstrated a favorable safety profile and was well tolerated for up to 156 weeks. These data continue to support the lack of accumulation of immunosuppression and a need for specific laboratory monitoring with APR. The incidence of AEs remained stable or decreased with long-term exposure to APR. <h3>Acknowledgement</h3> We thank Adewale O. Adebajo for his work on the original abstract. <h3>Disclosure of Interest</h3> P. Mease Grant/research support from: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, Celgene Corporation, Novartis, Roche, Consultant for: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, Celgene Corporation, Novartis, Roche, Speakers bureau: Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Genentech, Janssen, Eli Lilly, Pfizer, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer, Novartis, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer, Novartis, UCB, J. Gomez-Reino Grant/research support from: Roche, Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer Inc, Roche, Schering-Plough, UCB, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough, Wyeth, S. Hall Grant/research support from: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, Consultant for: Celgene Corporation, Pfizer, UCB, Bristol-Myers Squibb, Glaxo-Smith Kline, Roche, Janssen, Novartis, Merck, A. Kavanaugh Grant/research support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, 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, K. Shah Employee of: Celgene Corporation, L. Teng Employee of: Celgene Corporation, J. Wollenhaupt Grant/research support from: Abbott, Bristol-Myers Squibb, MSD, Pfizer, UCB, Consultant for: Abbott, Bristol-Myers Squibb, MSD, Pfizer, UCB