Background/Purpose: ACTIVE is the first apremilast (APR) trial that evaluated time to onset of efficacy beginning at Wk 2 in psoriatic arthritis (PsA) patients (pts) who were biologic-naïve and may have had ≤1 prior conventional disease-modifying antirheumatic drug. We report the study results through Wk 52.

Methods: Pts were randomized (1:1) to APR 30 mg BID or placebo (PBO). At Wk 16, pts whose swollen and tender joint counts (SJC/TJC) had not improved ≥10% were eligible for early escape (investigator discretion): PBO pts received APR, and APR pts continued on APR. At Wk 24, all pts entered the active treatment phase with APR. The primary endpoint was ACR20 response at Wk 16. Other assessments included changes in DAS-28 (CRP), SJC, TJC, and HAQ-DI, morning stiffness duration/severity, and enthesitis, as measured by the Gladman Enthesitis Index (GEI; 0=no enthesitis, 6=all 6 sites active). Along with collection of safety data, tolerability adverse events (AEs) of diarrhea were further characterized.

Results: A total of 219 pts were randomized (APR: n=110; PBO: n=109); 84.5% completed Wk 24 (APR: n=87; PBO: n=98). Separation in the proportion of ACR20 responders to APR vs PBO was noted at Wk 2 (16.4% vs 6.4%; P=0.0252), the first post-baseline (BL) visit. Early onset of response to APR was observed across clinical assessments, with improvements in DAS-28 (CRP), SJC, HAQ-DI, enthesitis, and morning stiffness severity (Table). At Wk 16, APR showed significant reduction in PsA disease activity and manifestations vs PBO, with an ACR20 response rate of 38.2% vs 20.2% (P=0.0040); DAS-28 (CRP) change of −1.07 vs −0.39 (P<0.0001); SJC change of −44.8% vs 1.9%; HAQ-DI change of −0.21 vs −0.06 (P=0.0229); improvement in morning stiffness severity in 46.4% vs 26.6% of pts; and GEI change of −1.5 vs −0.4 (P=0.0014). With continued APR exposure, the Wk 52 ACR20 response rate was 63.3%, ACR50 and ACR70 response rates were 32.4% and 14.0%, and percent change in SJC was −74.5%. Among APR pts with BL enthesitis, 62.8% reached a GEI of 0. Overall incidence of AEs in the PBO-controlled period was generally similar between APR and PBO. The most commonly reported AEs in ≥5% of pts with APR vs PBO were nasopharyngitis (8.3% vs 6.4%), nausea (8.3% vs 1.8%), headache (7.3% vs 3.7%), hypertension (6.4% vs 6.4%), and diarrhea (14.7% vs 11.0%); using a protocol-defined characterization of diarrhea (≥2 watery/liquid stools/day), overall incidence was lower for APR and PBO (11.0% and 8.3%). Serious AEs were lower with APR vs PBO (2.8% vs 4.6%). In general, no increase was seen in AE incidence/severity with longer-term exposure to APR.

Conclusion: In biologic-naïve pts treated with APR, onset of effect was observed starting with Wk 2, with sustained improvements across PsA manifestations, including morning stiffness and enthesitis through Wk 52. AEs were consistent with those reported for other APR phase III PsA and psoriasis studies.