Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

Abstract

Objective: Evaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.

Methods: Patients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52.

Results: Among 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast's safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0-24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo).

Conclusions: In biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports.

Trial registration number: NCT01925768; Results.

Keywords: Das28; disease activity; psoriatic arthritis; spondyloarthritis; treatment.

Figure 1

(A) ACR20 response, (B) mean per cent change in SJC and (C) mean per cent change in TJC through week 52. All data shown are as observed among patients as randomised at baseline and receiving at least one dose of apremilast. ACR20, 20% improvement in modified American College of Rheumatology response criteria; n/m, number of responders/number of patients with sufficient data for evaluation; SJC, swollen joint count; TJC, tender joint count.

Figure 2

Proportion of patients achieving a GEI of 0* through week 52. All data shown are as observed among patients as randomised at baseline, receiving at least one dose of apremilast and having pre-existing enthesopathy at baseline (eg, GEI score >0, n=102). GEI, Gladman Enthesitis Index; n/m, number of responders/number of patients with sufficient data for evaluation.

Figure 3

Mean change from baseline in HAQ-DI score through week 52. All data shown are as observed among patients as randomised at baseline and receiving at least one dose of apremilast. HAQ-DI, Health Assessment Questionnaire-Disability Index.