Background/Purpose: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to modulate inflammatory mediators. The PALACE 1, 2, and 3 trials compared the efficacy and safety of APR with placebo (PBO) in pts with active PsA despite prior DMARDs and/or biologics. The impact of APR on laboratory measurements was assessed in a pooled analysis of PALACE 1, 2, and 3.

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/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. Pts taking concurrent DMARDs were allowed to continue stable doses (MTX, sulfasalazine, leflunomide, or a combination). The analysis comprises all data from the APR-exposure periods (wks 0-≥52).

Results: 1,493 patients received study drug (PBO, 495; APR20, 501; APR30, 497) and were included in the safety population. The APR-exposure period included 720 pts treated with APR20 (766.4 pt-yrs) and 721 pts treated with APR30 (769.0 pt-yrs). Over the APR-exposure period, there were no clinically meaningful effects on laboratory measurements. Marked abnormalities in hematology and chemistry laboratory variables at any time during the exposure period were infrequent, with no treatment or dose effect evident. All marked hematological abnormalities occurred in a similar percentage of PBO pts vs APR pts during the PBO-controlled phase and continued without any significant changes during the APR-exposure period (wks 24-≥52). Overall, mean changes from BL clinical chemistry parameters were small and not clinically significant; no dose relationships were noted. Median values for both hematological and chemistry labs did not change meaningfully from BL during the trials. Most of the marked abnormal laboratory changes were transient, did not recur in spite of continuation of study drug, did not lead to study discontinuation, and were not clinically significant requiring specific treatment. Most pts had ALT and AST values ≤1 x ULN; ALT and AST values ≥3 x ULN were asymptomatic and transient with increased values returning to normal or BL in most pts despite continued treatment with APR, and similar to hematology parameters, without recurrence. There were no cases of liver function test elevations meeting Hy’s Law (ALT/AST ≥3 ULN along with bilirubin ≥2 ULN without relevant clinical finding may indicate potential for drug-induced liver injury) during the APR-exposure period.

Conclusion: APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks. No clinically meaningful effects on laboratory parameters were noted. These data do not indicate a need for laboratory monitoring.