<>Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate pro- and anti-inflammatory mediators. PALACE 2 compared the efficacy and safety of APR with placebo (PBO) in pts with active PsA despite prior DMARDs and/or biologics. <>Methods: Pts were randomized 1:1:1 to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30) stratified by baseline (BL) DMARD use. At wk 16, pts with <20% reduction from BL in swollen and tender joint counts qualified for protocol-defined early escape; those on PBO were re-randomized to APR20 or APR30 and those on APR remained on the initial APR dose. At wk 24, all remaining PBO pts were re-randomized to APR20 or APR30 through wk 52. Patients taking concurrent DMARDs were allowed to continue stable doses (MTX, sulfasalazine, leflunomide, or a combination). <>Results: 484 pts were randomized and received ≥1 dose of study drug (PBO, 159; APR20, 163; APR30, 162). At wk 16 (primary endpoint), a significantly greater proportion of pts treated with APR20 (38.4%; P=0.0002) and APR30 (34.4%; P=0.0024) achieved an ACR20 response vs PBO (19.5%). For those pts originally randomized to APR and completing 52 wks of study, improvements were maintained or increased over 52 wks for multiple endpoints, including: (1) ACR20 response of 52.9% (APR20) and 52.6% (APR30) (Figure); (2) HAQ-DI mean change from BL (SD) of -0.192 (0.573) for APR20 pts and -0.330 (0.509) for APR30 pts; (3) SF-36 Physical Functioning domain score mean change from BL (SD) of 5.05 (7.96) for APR20 pts and 6.35 (8.67) for APR30 pts; and (4), in these pts with BL BSA ≥3%, PASI-75/PASI-50 achievement of 27.1%/49.2% in APR20 pts and 39.3%/58.9% in APR30 pts. Pts randomized to APR at wks 16 and 24 demonstrated results consistent with those originally randomized to APR. APR was generally well tolerated. Adverse events (AEs) occurring in ≥5% of all pts exposed to APR through wk 52 were diarrhea, nausea, upper respiratory tract infection, headache, and nasopharyngitis. The majority of AEs were mild or moderate in severity and predominantly did not lead to discontinuation. Serious AEs (SAEs) occurred in 4.7% (APR20) and 5.1% (APR30) of pts as treated. No new safety findings were identified and the incidence of pts experiencing any AE was comparable over the 0-24 and 0-52 wk periods. No imbalance in the exposure-adjusted incidence rates of major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies between APR and PBO was observed. No cases of TB (novel or reactivation) were reported in the APR treatment groups; TB screening was not required per protocol. <>Conclusion: Over 52 wks, APR demonstrated long-term efficacy in the treatment of PsA, including clinically meaningful improvements in signs and symptoms and physical function. APR had an acceptable safety profile and was generally well tolerated for up to 52 wks.