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

• Limited 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.References[1]Dalakas MC, Hohlfeld R. Lancet 2003;362:971–82.[2]Tjärnlund A, et al. Ann Rheum Dis 2018;77:55–62.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Medical writing and editorial assistance were provided by Fiona Boswell, PhD, of Caudex and were funded by Bristol Myers Squibb. Study execution was by Sandra Overfield and Robin Scully.Disclosure of InterestsRohit Aggarwal Consultant of: AbbVie, Alexion, Argenx, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Corbus, CSL Behring, EMD Serono, Janssen, Jubilant, Kezar, Kyverna, Mallinckrodt, Octapharma, Orphazyme, Pfizer, Q32, Roivant (personal fees), Grant/research support from: Bristol Myers Squibb, EMD Serono, Genentech, Mallinckrodt, Pfizer, Q32, Ingrid E. Lundberg Shareholder of: Novartis, Roche, Consultant of: Argenx, AstraZeneca, Corbus, EMD Serono, Janssen, Kezar, Octapharma, Orphazyme (personal fees), Grant/research support from: Bristol Myers Squibb, Yeong Wook Song: None declared, Aziz Shaibani: None declared, Victoria P Werth Consultant of: AbbVie, Akari, Amgen, Argenx, AstraZeneca, Bayer, Beacon Bioscience, Biogen, Bristol Myers Squibb, Celgene, Corcept, Crisalis, CSL Behring, Cugene, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Horizon, Idera, Incyte, Janssen, Kezar, Kwoya Kirin, Lilly, Medimmune, Medscape, Merck, Nektar, Octapharma, Pfizer, Principia, Regeneron, Resolve, Rome Pharmaceuticals, Sanofi, UCB, Viela Bio, Grant/research support from: Amgen, Argenx, AstraZeneca, Biogen, Bristol Myers Squibb, Celgene, Corbus Pharmaceuticals, CSL Behring, Genentech, Gilead, Janssen, Pfizer, q32 Bio, Regeneron, Syntimmune, Ventus, Viela, Michael A Maldonado Employee of: Bristol Myers Squibb

Publikations- och innehållstyp

vet (ämneskategori)

kon (ämneskategori)