Apremilast provides sustained improvement in patients with psoriatic arthritis

Apremilast demonstrated continued improvements in several disease markers of psoriatic arthritis, with onset of efficacy occurring by Week 2, according to a 52-week analysis of the ACTIVE trial presented at the American College of Rheumatology Annual Meeting.

The ACTIVE trial enrolled biologic-naive patients who were randomly assigned 1:1 to treatment with apremilast (Otezla, Celgene Corporation) 30 mg twice per day or placebo. Patients whose swollen and tender joint counts did not improve by 10% or more were eligible for early escape, per investigator discretion, at Week 16. Patients in the placebo arm were switched to apremilast and patients originally assigned to treatment with apremilast continued receiving the agent. At Week 24, all patients entered active treatment with apremilast.

The primary endpoint of the ACTIVE trial was ACR20 response at Week 16. Other endpoints included changes in DAS28 C-reactive protein score (DAS28-CRP), swollen and tender joint counts, health assessment questionnaire–disability index (HAQ-DI), morning stiffness duration and severity, and enthesitis, as measured by the Gladman Enthesitis Index (GEI). Safety data was collected and the tolerability of diarrhea, an adverse event, was analyzed.

In total, 219 patients were included in the study. Of these, 110 patients were randomly assigned to treatment with apremilast and 109 patients were treated with placebo. At Week 24, 84.5% of patients had completed the study (apremilast, n = 87; placebo, n = 98). A separation in the number of patients who achieved ACR20 response was observed at Week 2 — the first visit after baseline — in the apremilast arm vs. the placebo arm (16.4% vs. 6.4%, respectively; P = .0252).

Early onset of response to apremilast was noted in clinical assessments. Apremilast demonstrated a reduction in disease activity and manifestations of psoriatic arthritis at Week 16 compared with placebo. The ACR20 response rate for apremilast was 38.2% compared with 20.2% for placebo (P = .0040). A change of −1.07 in the DAS28-CRP score was noted with apremilast compared with −0.39 for placebo (P < .0001). Change in swollen and tender joint counts was −44.8% for apremilast compared with 1.9% for placebo. Change in the HAQ-DI score was −0.21 for apremilast compared with −0.06 for placebo (P = .0229). The GEI change was −1.5 for apremilast compared with −0.4 for placebo (P = .0014). Improvement in the severity of morning stiffness was 46.4% for patients who received apremilast and 26.6% for patients who received placebo.

Continued exposure to apremilast resulted in ACR20, ACR50 and ACR70 responses of 63.3%, 32.4% and 14%, respectively, at Week 52. The percent change in swollen and tender joint counts was −74.5%. Patients with baseline enthesitis who were treated with apremilast achieved a GEI score of 0.

The rate of adverse events during the placebo-controlled period were generally similar between patients treated with apremilast and patients who received placebo. The most frequently reported adverse events in at least 5% of patients who received apremilast compared with placebo 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%). A protocol-defined characterization of diarrhea (of at least two watery/liquid stools per day) demonstrated the overall incidence was lower for apremilast and placebo (11% and 8.3%, respectively). There were fewer reports of serious adverse events with apremilast than with placebo (2.8% vs. 4.6%). In general, researchers found no increase in the incidence or severity of adverse events associated with longer-term exposure to apremilast.

“In biologic-naive patients treated with [apremilast], onset of effect was observed starting with [Week] 2, with sustained improvements across [psoriatic arthritis] manifestations, including morning stiffness and enthesitis, through [Week] 52,” the researchers wrote. “[Adverse events] were consistent with those reported for other [apremilast] phase 3 [psoriatic arthritis] and psoriasis studies.” – by Julia Ernst, MS

Reference:

Nash P, et al. Abstract 1703. Presented at: The American College of Rheumatology Annual Meeting; Nov. 11-16, 2016. Washington.

Disclosures: Nash reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.