POS0839 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL TO EVALUATE EFFICACY AND SAFETY OF SC ABATACEPT IN ADULTS WITH ACTIVE IDIOPATHIC INFLAMMATORY MYOPATHY

Abstract

BackgroundLimited therapies are available for patients with idiopathic inflammatory myopathy (IIM), a heterogenous group of chronic, systemic, autoimmune inflammatory diseases characterized by progressive muscle weakness and/or distinct skin rashes.1 Abatacept, a selective co-stimulation modulator, may be a useful treatment option.2ObjectivesTo evaluate efficacy, safety, and tolerability of abatacept + standard of care (SOC) in patients with IIM compared with SOC alone (placebo).MethodsA 24-week, randomized, double-blind, placebo-controlled phase 3 trial of SC abatacept (125 mg weekly) + SOC (corticosteroids and immunosuppressants alone or combined; NCT02971683) in patients with active, treatment-refractory IIM (Manual Muscle Testing-8 [MMT-8] ≤ 135) was performed. Primary endpoint was proportion of patients meeting International Myositis Assessment and Clinical Studies definition of improvement (IMACS DOI) at week 24. Change from baseline in myositis Functional Index-2 (FI-2), HAQ-DI, Myositis Disease Activity Assessment Tool (MDAAT), and Myositis Response Criteria (MRC) were secondary endpoints with safety. Post hoc analyses by disease subtype were performed.ResultsOverall, 148 patients were randomized (75 abatacept; 73 placebo); IIM subtypes were dermatomyositis (DM; 53.3% vs 57.5%), polymyositis (PM; 25.3% vs 34.2%), and autoimmune necrotizing myopathy (ANM; 21.3% vs 8.2%). Mean baseline MMT-8 and HAQ-DI scores were 112.7 and 1.5, respectively. Approximately 90% of patients completed week 24. Week 24 IMACS DOI rates were abatacept 56.0% vs placebo 42.5% (adjusted odds ratio, 1.8 [95% CI, 0.9–3.5]; P = 0.083). Pre-specified IMACS DOI analysis showed no differences for patients with DM but notable benefit for those with non-DM subtypes, PM and ANM (Table 1). Secondary endpoints showed similar differences (Table 1). MRC at day 169 by category is shown in Figure 1. Proportion of AEs (69.3% and 75.3%) and serious AEs (5.3% and 5.5%) were similar in the abatacept and placebo arms.Table 1.Primary and secondary (mean change from baseline at week 24) endpointsOutcomeIIMAbataceptPlaceboNominal P value (abatacept vs placebo) or adjusted mean difference from placebo (95% CI)IMACS DOI,a n/N (%)All42/75 (56.0)31/73 (42.5)P = 0.083DM22/40 (55.0)21/42 (50.0)P = 0.679Non-DM20/35 (57.1)10/31 (32.3)P = 0.040FI-2All4.1 (1.3)1.2 (1.4)2.9 (0 to 5.8)DM2.3 (1.6)0.3 (1.4)1.9 (−2.3 to 6.2)Non-DM3.2 (1.4)−0.6 (1.5)3.7 (−0.3 to 7.8)HAQ-DIAll−0.31 (0.07)0.20 (0.07)−0.12 (−0.28 to 0.04)DM−0.31 (0.08)−0.19 (0.07)−0.11 (−0.32 to 0.10)Non-DM−0.25 (0.09)−0.07 (0.09)−0.18 (−0.44 to 0.07)MDAAT, Extramuscular Global Activity, (95% CI)bAll−1.56 (−1.96 to −1.16)−1.40 (−1.81 to −0.99)−0.16 (−0.63 to 0.30)DM−1.90 (−2.43 to −1.37)−1.85 (−2.35 to 1.36)−0.05 (−0.77 to 0.68)Non-DM−1.09 (−1.46 to −0.72)−0.85 (−1.27 to −0.43)−0.24 (−0.80 to 0.32)MMT-8All12.9 (1.9)11.0 (2.0)1.8 (−2.7 to 6.4)DM14.4 (2.2)14.0 (2.2)0.4 (−5.7 to 6.4)Non-DM12.1 (2.5)7.8 (2.7)4.3 (−3.0 to 11.7)Physician Global AssessmentbAll−2.89 (0.30)−2.69 (0.30)−0.20 (−0.92 to 0.52)DM−2.78 (0.29)−2.43 (0.28)−0.35 (−1.15 to 0.46)Non-DM−2.35 (0.43)−2.21 (0.48)−0.14 (−1.43 to 1.15)Patient Global AssessmentbAll−1.4 (0.31)−0.98 (0.32)−0.38 (−1.11 to 0.35)DM−1.4 (0.33)−1.4 (0.31)−0.00 (−0.91 to 0.90)Non-DM−1.2 (0.41)−0.3 (0.44)−0.93 (−2.14 to 0.29)Data are adjusted mean change from baseline score (SE) unless stated.aDefined as improvement of ≥ 20% in 3 IMACS core measures, worsening by ≥ 25% in ≤ 2 IMACS core measure scores, and a reduction of < 25% in MMT-8; b100 mm visual analog scale.ConclusionIn this double-blind trial of SC abatacept vs placebo, abatacept failed to meet primary or secondary endpoints. Post hoc analyses suggest a treatment benefit in patients with PM and ANM (not DM) when treated with abatacept. Abatacept use was well tolerated.