Neurology 2021 Feb 17. Epub 2021 Feb 17.
From the Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA (A.A.A.); Medical Research Council (MRC) Centre for Neuromuscular Diseases, University College London (UCL) Institute of Neurology, London, UK (M.G.H., P.M.M.); Department of Neuromuscular Diseases & Centre for Rheumatology, University College London, London, UK (P.M.M.); Department of Rheumatology & Queen Square Centre for Neuromuscular Diseases, University College London Hospitals NHS Foundation Trust, London, UK (P.M.M.); and Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK (P.M.M.); Department of Neurology, Leiden University Medical Center, Leiden, Netherlands (U.A.B.); National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK (H.C.); Department of Internal Medicine and Clinical Immunology, Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France (O.B.); Novartis Healthcare Pvt. Ltd., Hyderabad, India (K.A.K); Novartis Pharmaceuticals, East Hanover, NJ, USA (M.W., D.A.P.); Novartis Pharma AG, Basel, Switzerland (L.B.T., A.A.S-T.); Novartis Pharma AG, Basel, Switzerland; ‡UCB, Switzerland (L.Z.A.); Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA (T.E.L.); Fiona Stanley Hospital, Institute for Immunology & Infectious Diseases Murdoch University and Notre Dame University, Perth, Australia (M.N.); Department of Neurology, Royal North Shore Hospital, New South Wales, Australia (C.L.); Calvary Health Care Bethlehem, Caulfield South, Australia (K.A.R.); Department of Neurology, Amsterdam University Medical Centre, Amsterdam, The Netherlands (M.d.V); Department of Medicine, University of Miami, Miami, FL, USA (D.P.A.); Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA (R.J.B., M.M.D.); Department of Neurology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK (J.A.L.M.); Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA (J.T.K.); UC Davis School of Medicine, Neuromuscular Research Center, Sacramento, CA, USA; ‡Department of Neurology, Mayo Clinic, Jacksonville, FL, USA (B.O.); UC Davis School of Medicine, Neuromuscular Research Center, Sacramento, CA, USA (N.C.J.); Department of Neurology, University Hospital Saint-Luc, University of Louvain, Brussels, Belgium (P.V.d.B.); Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium and the Institute Born-Bunge, University of Antwerp, Antwerp, Belgium (J.B.); Department of Neurology, Ghent University Hospital, Ghent, Belgium (J.L.d.B.); Department of Neurology, Oregon Health & Science University, Portland, OR, USA (C.K.); Department of Neurology, Massachusetts General Hospital, Neuromuscular Diagnostic Center and Electromyography Laboratory, Boston, MA, USA (W.S.D.); Department of Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy (M.M.); Università Cattolica del Sacro Cuore, Rome, Italy (M.M.); Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA (S.P.N.); Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland (H.H.J.); Department of Neurosciences, University of Padova School of Medicine, Padova, Italy (E.P.); Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy (L.M.); Unit of Neurology and Neuromuscular Disorders, Azienda Ospedaliera Universitaria Policlinico G Martino, University of Messina, Messina, Italy (C.R.); Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, Brescia, Italy (M.F.); Nerve and Muscle Center of Texas, Houston TX, USA (A.I.S.); Neuromuscular Research Center, Phoenix, AZ, USA (K.S.); Department of Neurology, University of California Irvine, ALS & Neuromuscular Center, Orange, CA, USA (N.A.G.); Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan (M.M-Y.); Department of Neurology, Kumamoto University Hospital, Kumamoto, Japan (S.Y.); Department of Neurology, Tohoku University Hospital, Miyagi, Japan (N.S.); Department of Neurology, Tohoku University School of Medicine, Sendai, Japan (M.A.); Department of Neurology, Nagoya University Hospital, Nagoya, Aichi, Japan (M.K.); Department of Neurology, Osaka City General Hospital, Osaka, Japan (H.M.); Wakayama Medical University Hospital, Wakayama, Japan (K.M.); Tokushima University Hospital, Tokushima, Japan; Department of Neurology, Kanazawa Medical University, Ishikawa, Japan (H.N.); Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan (I.N.); RTI Health Solutions, Research Triangle Park, NC, USA (C.D.R., V.S.L.W.); and Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Denmark (J.V.) Present affiliation.
Objective: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis.
Methods: Participants (aged 36-85 years) who completed the core study (RESILIENT) were invited to join an extension study. Individuals continued on same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab, or matching placebo administered as intravenous infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety.
Results: Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively).
Conclusion: Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint.
Classification Of Evidence: This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well tolerated and did not provide meaningful functional benefit. The study is rated Class IV because of the open label design of Extension Treatment Period 2.
Clinical Trial Registration: Registered at ClinicalTrials.gov: NCT02573467.