Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis

Abstract

Objectives: To assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).

Methods: This study randomised patients (1:1) with active PsA (~60% with prior exposure to a tumour necrosis factor inhibitor) to blinded weekly subcutaneous abatacept 125 mg (n=213) or placebo (n=211) for 24 weeks, followed by open-label subcutaneous abatacept. Patients without ≥20% improvement in joint counts at week 16 were switched to open-label abatacept. The primary end point was the proportion of patients with ≥20% improvement in the American College of Rheumatology (ACR20) criteria at week 24.

Results: Abatacept significantly increased ACR20 response versus placebo at week 24 (39.4% vs 22.3%; p<0.001). Although abatacept numerically increased Health Assessment Questionnaire-Disability Index response rates (reduction from baseline ≥0.35) at week 24, this was not statistically significant (31.0% vs 23.7%; p=0.097). The benefits of abatacept were seen in ACR20 responses regardless of tumour necrosis factor inhibitor exposure and in other musculoskeletal manifestations, but significance could not be attributed due to ranking below Health Assessment Questionnaire-Disability Index response in hierarchical testing. However, the benefit on psoriasis lesions was modest. Efficacy was maintained or improved up to week 52. Abatacept was well tolerated with no new safety signals.

Conclusions: Abatacept treatment of PsA in this phase III study achieved its primary end point, ACR20 response, showed beneficial trends overall in musculoskeletal manifestations and was well tolerated. There was only a modest impact on psoriasis lesions.

Trial registration number: ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb).

Keywords: DMARDs (biologic); Psoriatic arthritis; T cells; Treatment.

Figure 1

Patient disposition. SC, subcutaneous. *Includes missing (n=2).

Figure 2

ACR20 response over the 24-week double-blind period (non-responder imputation for early escape). Early escape patients switching to open-label abatacept at week 16 were imputed as non-responders at weeks 20 and 24. If there were still missing data, patients were imputed as non-responders, unless data were missing between two time points at which the patient had a response, in which case response was imputed. #Where 95% CI of estimate of differences in ACR20 responses for abatacept versus placebo do not contain zero. ACR20, ≥20% improvement in the American College of Rheumatology criteria.

Figure 3

Proportion of patients achieving ACR20 response (ITT analysis, actual data for early escape patients) over the combined double-blind and open-label periods in the total population (A) and the TNFi-naïve (B) and TNFi-exposed (C) subgroups. Error bars represent 95% CIs. For EE patients, measurements at weeks 20, 24, 28, 36 and 44 are actual measurements at weeks 4, 8, 12, 20 and 28 of open-label abatacept treatment. The increase in the proportion of patients with ACR20 response from week 16 to week 24 in the placebo group reflects the mixed population of EE patients who received abatacept between weeks 16 and 24 and non-EE patients who received placebo at week 24. If there were missing data, patients were imputed as non-responders, unless data were missing between two time points at which the patient had a response, in which case response was imputed. ACR20, ≥20% improvement in the American College of Rheumatology criteria; EE, early escape; ITT, intent to treat; TNFi, tumour necrosis factor inhibitor.