Background/Purpose: Apremilast (APR) is a phosphodiesterase 4 inhibitor that helps regulate the immune response that causes inflammation and skin disease associated with psoriatic arthritis (PsA). PALACE 4 compared the efficacy and safety of APR with placebo (PBO) in patients with active PsA who were DMARD-naïve. We evaluated the impact of APR treatment over 52 weeks on enthesitis and dactylitis among PALACE 4 patients.

Methods: Patients were randomized (1:1:1) to PBO, APR 20 mg BID (APR20), or APR 30 mg BID (APR30). Patients whose swollen and tender joint counts had not improved by ≥20% at Week 16 were considered non-responders and were required to be re-randomized (1:1) to APR20 or APR30 if initially randomized to placebo, or continued on their initial apremilast dose. At Week 24, all remaining PBO patients were re-randomized to APR20 or APR30. The analysis comprises data from Weeks 0 to 52. Enthesitis was evaluated based on MASES (range 0-13), which indicates the number of painful entheses out of 13 entheses sites. The dactylitis count (range 0-20) is the number of digits (hands and feet) with dactylitis present; each digit is rated as 0 (no dactylitis) or 1 (dactylitis present).

Results: At Week 16, a significantly greater proportion of patients receiving APR20 or APR30 achieved the modified ACR20 response vs PBO (primary endpoint). In patients initially randomized to APR and with enthesitis (n=228) or dactylitis (n=173) at baseline, APR was associated with improvements in enthesitis and dactylitis over 52 weeks, as evidenced by reductions in MASES and dactylitis count. At Week 16, median percent changes in MASES were 0.0% (PBO), -20.0% (APR20; P=0.2948), and -50.0% (APR30; P=0.0008). In patients initially randomized to APR and completing 52 weeks, median percent changes in MASES were -66.7% (APR20) and -75% (APR30) (Table); 39.6% (APR20) and 45.9% (APR30) of patients achieved a score of 0, indicating no pain at any of the entheses assessed. Median percent changes in dactylitis count at Week 16 were -50.0% (PBO), -70.8% (APR20; P=0.0691), and -69.2% (APR30; P=0.1494). In patients initially randomized to APR and completing 52 weeks, both doses resulted in a median 100% decrease in the dactylitis count; a dactylitis count of 0 was achieved in 68.6% (APR20) and 68.8% (APR30) of patients. The most common adverse events reported during the PBO-controlled period were nausea (12.6%), diarrhea (9.4%), and headache (6.0%). The safety profile of APR for up to 52 weeks was similar to that observed with APR for up to 24 weeks of treatment (PBO-controlled period).

Conclusion: Among patients continuously treated with APR through 52 weeks, sustained improvements in both enthesitis and dactylitis were observed in patients with active PsA, who had enthesitis or dactylitis at baseline. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 weeks.