Efficacy and Safety of Subcutaneous Abatacept Plus Standard Treatment for Active Idiopathic Inflammatory Myopathy: Phase 3 Randomized Controlled Trial

Abstract

Objective: Our objective was to evaluate the efficacy and safety of subcutaneous (SC) abatacept and standard of care (SOC) for the treatment of idiopathic inflammatory myopathy (IIM) over 52 weeks.

Methods: In this randomized, double-blind, placebo-controlled phase III trial, patients with treatment-refractory IIM received SC abatacept (at 125 mg weekly) with SOC (abatacept group) or a placebo with SOC (placebo group). A 24-week double-blind period was followed by an open-label period to assess outcomes from continued therapy with abatacept and initiation with abatacept (placebo-to-abatacept switch group) from 24 to 52 weeks. The primary end point was International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Secondary efficacy and safety end points were assessed.

Results: Overall, 148 (double-blind) and 133 (open-label) patients were treated. Baseline demographics were well-balanced between treatment groups and disease subtypes. At 24 weeks, improvement per IMACS DOI was 56.0% for the abatacept group and 42.5% for the placebo group (P = 0.083); at 52 weeks, improvement was 69.8% (continued abatacept) and 69.0% (placebo-to-abatacept switch). The IMACS DOI rate at 24 weeks was greater in the nondermatomyositis (non-DM) group (abatacept: 57.1%; placebo: 32.3%; P = 0.040) than the DM group (abatacept: 55.0%; placebo: 50.0%; P = 0.679). The observed safety profile was similar in both groups.

Conclusion: The proportion of patients who met improvement criteria after 24 weeks was similar between abatacept and placebo groups. However, analysis by IIM subtype suggested there may be a sustained benefit of SC abatacept for patients with non-DM subtypes.

Figure 1

Patient disposition. *One patient was randomly assigned but not treated, leaving 148 randomly assigned and treated. ^†Includes patient request to discontinue treatment and patient withdrew consent. DB, double‐blind; OL, open label. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.43066/abstract.

Figure 2

MRC at week 24 by TIS category (intent‐to‐treat analysis population). DM, dermatomyositis; IMNM, immune‐mediated necrotizing myopathy; MRC, Myositis Response Criteria; PM, polymyositis; TIS, Total Improvement Score.