Background Apremilast (APR) modulates a network of pro- and anti-inflammatory mediators.
Objectives The PALACE 1 study compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA despite prior DMARDs and/or biologics over 24 wks. At wk 24, all patients were randomized to APR through wk 52.
Methods Patients were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). At wk 16, patients with <20% reduction from baseline in swollen/tender joint counts were re-randomized to APR20 or APR30 (PBO group), or remained on their initial APR dose. At wk 24, all remaining PBO patients were re-randomized to APR20 or APR30 through wk 52.
Results 504 patients were randomized. At wk 16, significantly more APR20 (31.3%; P=0.0140) and APR30 patients (40.0%; P<0.0001) achieved an ACR20 vs PBO (19.4%). At wk 52, all patients had a minimum 28 wks of APR exposure. Response to APR was generally maintained over the treatment period. At wk 52, ACR20 was achieved by 63.0% (APR20) and 54.6% (APR30) of patients (Table). Exposure-adjusted incidence rates for adverse events (AEs), severe AEs, and serious AEs were comparable between 0-24 and 0-52 wks. The proportion of patients remaining on APR to wk 52 who first reported the most common GI disturbances (eg, diarrhea, nausea, and vomiting) after wk 24 was low (ranging from 0.6-3% for APR20 and 0-1.8% for APR30). There were no clinically meaningful laboratory findings with exposure up to 52 wks. No deaths beyond the 1 previously reported in the 0-24 wk period were observed in the 24-52 wk period. No safety signals with respect to major cardiac events, malignancies, and opportunistic infections were observed, consistent with the 0-24 wk period. No cases of lymphoma, tuberculosis, or tuberculosis reactivations were reported for the 52-wk period.
Conclusions Apremilast administered to patients with PsA beyond 24 wks continued to demonstrate meaningful clinical response. For patients who completed 52 wks of the study, ACR20 response rates up to 65% were observed. Apremilast continued to be well tolerated with an acceptable longer-term safety profile.
Disclosure of Interest A. Kavanaugh Grant/research support from: Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Celgene, Centocor-Janssen, Pfizer, Roche and UCB, P. Mease Grant/research support from: Abbvie, Amgen, BiofenIdec, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Glaxo SmithKline, Lilly, Merck, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BiofenIdec, Bristol-Myers Squibb, Genentech, Janssen, Glaxo SmithKline, Lilly, Pfizer, UCB, A. Adebajo: None Declared, J. Wollenhaupt Consultant for: Abbott Laboratories, Bristol-Myers Squibb, MSD, Pfizer and UCB, C. Hu Employee of: Celgene Corporation, K. Shah Employee of: Celgene Corporation, R. Stevens Employee of: Celgene Corporation, J. Gomez-Reino Grant/research support from: Roche and Schering-Plough, Consultant for: Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough and UCB SA, Speakers bureau: Bristol-Myers Squibb, Roche, Schering-Plough and Wyeth