Articular and Extra-Articular Benefits in ACR20 Non-responders at Week 104 Treated With Apremilast: Pooled Analysis of Three Randomized Controlled Trials

Abstract

Introduction: PALACE 1, 2, and 3 were phase 3 studies aimed to evaluate apremilast efficacy and safety in patients with active psoriatic arthritis (PsA) despite prior treatment with conventional disease-modifying anti-rheumatic drugs and/or biologics. The pooled analysis reported here further characterized the clinical outcomes associated with long-term apremilast exposure in patients failing to achieve ≥ 20% improvement in the American College of Rheumatology response criteria (ACR20) at Week 104.

Methods: Patients randomized to apremilast 30 mg twice daily at baseline and classified as ACR20 non-responders (ACR20NRs) or ACR20 responders (ACR20Rs) at Week 104 were included. Efficacy outcomes included change from baseline to Week 104 in ACR core components and other endpoints.

Results: At Week 104, a total of 109 patients were ACR20NRs and 193 were ACR20Rs. As expected, the ACR20R group had improvements in all indices assessed. The ACR20NR group demonstrated substantial mean improvements from baseline in swollen joint count (SJC; - 58%), tender joint count (TJC; - 42%), and Physician's Global Assessment of Disease Activity (PhGA; - 44%); resolution of enthesitis (34%) and dactylitis (68%); and achievement of ≥ 75% reduction from baseline Psoriasis Area and Severity Index scores (among patients with psoriasis involving ≥ 3% of the body surface area) (36%).

Conclusion: Despite not fulfilling a formal ACR20 response at Week 104, ACR20NRs experienced sustained improvements in several PsA core domains, including SJC, TJC, enthesitis, dactylitis, and psoriasis, as well as the PhGA (visual analog scale) scores, with apremilast treatment.

Trial registration: ClinicalTrials.gov identifier: NCT01172938, NCT01212757, and NCT01212770.

Keywords: ACR20 non-responders; Apremilast; Articular; Extra-articular; Psoriatic arthritis.

Fig. 1

Proportion of ACR20NRs (a) and ACR20Rs (b) achieving ACR-n categories over 104 weeks and proportion of ACR20NRs (c) and ACR20Rs (d) achieving cDAPSA categories over 104 weeks. Data as observed. ACR20 is a composite measure defined as an improvement of 20% in swollen and tender joint counts and a 20% improvement in three of the five remaining ACR core set measures: Physician’s Global Assessment of Disease Activity, Patient’s Global Assessment of Disease Activity, Patient’s Assessment of Pain, Patient’s Assessment of Physical Function, and erythrocyte sedimentation rate or C-reactive protein [9]. ACR20 ≥ 20% improvement in American College of Rheumatology response criteria, ACR20NR ACR20 non-responder, ACR20R ACR20 responder, cDAPSA Clinical Disease Activity Index for Psoriatic Arthritis, HDA high disease activity, LDA low disease activity, ModDA moderate disease activity, REM remission

Fig. 2

Median percentage change in SJC (a) and TJC (b). Data as observed in patients randomized to apremilast 30 mg BID at baseline who were classified as ACR20Rs or ACR20NRs at Week 104. BID twice daily, SJC swollen joint count, TJC tender joint count

Fig. 3

Achievement of clinically meaningful scores in categorical outcomes at Week 104. Data as observed in patients randomized to apremilast 30 mg BID at baseline. ^aAmong patients with enthesitis at baseline. ^bAmong patients with dactylitis at baseline. ^cAmong patients with baseline psoriasis involvement ≥ 3% of the body surface area