Anthony A Amato1, Michael G Hanna2, Pedro M Machado2, Umesh A Badrising2, Hector Chinoy2, Olivier Benveniste2, Ananda Krishna Karanam2, Min Wu2, László B Tankó2, Agnes Annette Schubert-Tennigkeit2, Dimitris A Papanicolaou2, Thomas E Lloyd2, Merrilee Needham2, Christina Liang2, Katrina A Reardon2, Marianne de Visser2, Dana P Ascherman2, Richard J Barohn2, Mazen M Dimachkie2, James A L Miller2, John T Kissel2, Björn Oskarsson2, Nanette C Joyce2, Peter Van den Bergh2, Jonathan Baets2, Jan L De Bleecker2, Chafic Karam2, William S David2, Massimiliano Mirabella2, Sharon P Nations2, Hans H Jung2, Elena Pegoraro2, Lorenzo Maggi2, Carmelo Rodolico2, Massimiliano Filosto2, Aziz I Shaibani2, Kumaraswamy Sivakumar2, Namita A Goyal2, Madoka Mori-Yoshimura2, Satoshi Yamashita2, Naoki Suzuki2, Masashi Aoki2, Masahisa Katsuno2, Hirokazu Morihata2, Kenya Murata2, Hiroyuki Nodera2, Ichizo Nishino2, Carla D Romano2, Valerie S L Williams2, John Vissing2, Lixin Zhang Auberson2. 1. From the Department of Neurology (A.A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Medical Research Council Centre for Neuromuscular Diseases (M.G.H., P.M.M.) and Institute of Neurology, Department of Neuromuscular Diseases & Centre for Rheumatology (P.M.M.), University College London; Department of Rheumatology & Queen Square Centre for Neuromuscular Diseases (P.M.M.), University College London Hospitals NHS Foundation Trust; Department of Rheumatology (P.M.M.), Northwick Park Hospital, London North West University Healthcare NHS Trust, UK; Department of Neurology (U.A.B.), Leiden University Medical Center, Netherlands; National Institute for Health Research Manchester Biomedical Research Centre (H.C.), Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, UK; Department of Internal Medicine and Clinical Immunology (O.B.), Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; Novartis Healthcare Pvt. Ltd. (K.A.K), Hyderabad, India; Novartis Pharmaceuticals (M.W., D.A.P.), East Hanover, NJ; Novartis Pharma AG (L.B.T., A.A.S-T.), Basel, Switzerland; Department of Neurology (T.E.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Institute for Immunology & Infectious Diseases (M.N.), Fiona Stanley Hospital, Murdoch University and Notre Dame University, Perth; Department of Neurology (C.L.), Royal North Shore Hospital, New South Wales; Calvary Health Care Bethlehem (K.A.R.), Caulfield South, Australia; Department of Neurology (M.d.V), Amsterdam University Medical Centre, the Netherlands; Department of Medicine (D.P.A.), University of Miami, FL; Department of Neurology (R.J.B., M.M.D.), University of Kansas Medical Center, Kansas City; Department of Neurology (J.A.L.M.), Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; Department of Neurology (J.T.K.), The Ohio State University Wexner Medical Center, Columbus; Neuromuscular Research Center (B.O., N.C.J.), UC Davis School of Medicine, Sacramento, CA; Department of Neurology (P.V.d.B.), University Hospital Saint-Luc, University of Louvain, Brussels; Neuromuscular Reference Centre, Department of Neurology (J.B.), Antwerp University Hospital; Institute Born-Bunge (J.B.), University of Antwerp; Department of Neurology (J.L.d.B.), Ghent University Hospital, Belgium; Department of Neurology (C.K.), Oregon Health & Science University, Portland; Department of Neurology (W.S.D.), Massachusetts General Hospital, Neuromuscular Diagnostic Center and Electromyography Laboratory, Boston; Department of Neurology (M.M.), Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Università Cattolica del Sacro Cuore (M.M.), Rome, Italy; Department of Neurology (S.P.N.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (H.H.J.), University Hospital and University of Zurich, Switzerland; Department of Neurosciences (E.P.), University of Padova School of Medicine; Fondazione IRCCS Istituto Neurologico Carlo Besta (L.M.), Milan; Unit of Neurology and Neuromuscular Disorders (C.R.), Azienda Ospedaliera Universitaria Policlinico G Martino, University of Messina; Center for Neuromuscular Diseases (M.F.), Unit of Neurology, ASST Spedali Civili and University of Brescia, Italy; Nerve and Muscle Center of Texas (A.I.S.), Houston; Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (N.A.G.), ALS & Neuromuscular Center, University of California Irvine, Orange; Department of Neurology (M.M.-Y.), National Center Hospital, National Center of Neurology and Psychiatry, Tokyo; Department of Neurology (S.Y.), Kumamoto University Hospital; Department of Neurology (N.S.), Tohoku University Hospital, Miyagi; Department of Neurology (M.A.), Tohoku University School of Medicine, Sendai; Department of Neurology (M.K.), Nagoya University Hospital, Aichi; Department of Neurology (H.M.), Osaka City General Hospital; Wakayama Medical University Hospital (K.M.); Tokushima University Hospital (H.N.); Department of Neuromuscular Research (I.N.), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; RTI Health Solutions (C.D.R., V.S.L.W.), Research Triangle Park, NC; Copenhagen Neuromuscular Center (J.V.), Rigshospitalet, University of Copenhagen, Denmark; and UCB (L.Z.A.), Bulle, Switzerland. H.N. is currently affiliated with the Department of Neurology, Kanazawa Medical University, Ishikawa, Japan. B.O. is currently affiliated with the Department of Neurology, Mayo Clinic, Jacksonville, FL. aamato@bwh.harvard.edu. 2. From the Department of Neurology (A.A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Medical Research Council Centre for Neuromuscular Diseases (M.G.H., P.M.M.) and Institute of Neurology, Department of Neuromuscular Diseases & Centre for Rheumatology (P.M.M.), University College London; Department of Rheumatology & Queen Square Centre for Neuromuscular Diseases (P.M.M.), University College London Hospitals NHS Foundation Trust; Department of Rheumatology (P.M.M.), Northwick Park Hospital, London North West University Healthcare NHS Trust, UK; Department of Neurology (U.A.B.), Leiden University Medical Center, Netherlands; National Institute for Health Research Manchester Biomedical Research Centre (H.C.), Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, UK; Department of Internal Medicine and Clinical Immunology (O.B.), Pitié-Salpêtrière Hospital, Sorbonne Université, Paris, France; Novartis Healthcare Pvt. Ltd. (K.A.K), Hyderabad, India; Novartis Pharmaceuticals (M.W., D.A.P.), East Hanover, NJ; Novartis Pharma AG (L.B.T., A.A.S-T.), Basel, Switzerland; Department of Neurology (T.E.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Institute for Immunology & Infectious Diseases (M.N.), Fiona Stanley Hospital, Murdoch University and Notre Dame University, Perth; Department of Neurology (C.L.), Royal North Shore Hospital, New South Wales; Calvary Health Care Bethlehem (K.A.R.), Caulfield South, Australia; Department of Neurology (M.d.V), Amsterdam University Medical Centre, the Netherlands; Department of Medicine (D.P.A.), University of Miami, FL; Department of Neurology (R.J.B., M.M.D.), University of Kansas Medical Center, Kansas City; Department of Neurology (J.A.L.M.), Newcastle upon Tyne Hospitals NHS Foundation Trust, UK; Department of Neurology (J.T.K.), The Ohio State University Wexner Medical Center, Columbus; Neuromuscular Research Center (B.O., N.C.J.), UC Davis School of Medicine, Sacramento, CA; Department of Neurology (P.V.d.B.), University Hospital Saint-Luc, University of Louvain, Brussels; Neuromuscular Reference Centre, Department of Neurology (J.B.), Antwerp University Hospital; Institute Born-Bunge (J.B.), University of Antwerp; Department of Neurology (J.L.d.B.), Ghent University Hospital, Belgium; Department of Neurology (C.K.), Oregon Health & Science University, Portland; Department of Neurology (W.S.D.), Massachusetts General Hospital, Neuromuscular Diagnostic Center and Electromyography Laboratory, Boston; Department of Neurology (M.M.), Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Università Cattolica del Sacro Cuore (M.M.), Rome, Italy; Department of Neurology (S.P.N.), University of Texas Southwestern Medical Center, Dallas; Department of Neurology (H.H.J.), University Hospital and University of Zurich, Switzerland; Department of Neurosciences (E.P.), University of Padova School of Medicine; Fondazione IRCCS Istituto Neurologico Carlo Besta (L.M.), Milan; Unit of Neurology and Neuromuscular Disorders (C.R.), Azienda Ospedaliera Universitaria Policlinico G Martino, University of Messina; Center for Neuromuscular Diseases (M.F.), Unit of Neurology, ASST Spedali Civili and University of Brescia, Italy; Nerve and Muscle Center of Texas (A.I.S.), Houston; Neuromuscular Research Center (K.S.), Phoenix, AZ; Department of Neurology (N.A.G.), ALS & Neuromuscular Center, University of California Irvine, Orange; Department of Neurology (M.M.-Y.), National Center Hospital, National Center of Neurology and Psychiatry, Tokyo; Department of Neurology (S.Y.), Kumamoto University Hospital; Department of Neurology (N.S.), Tohoku University Hospital, Miyagi; Department of Neurology (M.A.), Tohoku University School of Medicine, Sendai; Department of Neurology (M.K.), Nagoya University Hospital, Aichi; Department of Neurology (H.M.), Osaka City General Hospital; Wakayama Medical University Hospital (K.M.); Tokushima University Hospital (H.N.); Department of Neuromuscular Research (I.N.), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; RTI Health Solutions (C.D.R., V.S.L.W.), Research Triangle Park, NC; Copenhagen Neuromuscular Center (J.V.), Rigshospitalet, University of Copenhagen, Denmark; and UCB (L.Z.A.), Bulle, Switzerland. H.N. is currently affiliated with the Department of Neurology, Kanazawa Medical University, Ishikawa, Japan. B.O. is currently affiliated with the Department of Neurology, Mayo Clinic, Jacksonville, FL.
Abstract
OBJECTIVE: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). METHODS: Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV 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) of 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 the 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. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573467. 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.
OBJECTIVE: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). METHODS: Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV 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) of 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 the 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. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573467. 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.
Authors: Anthony A Amato; Kumaraswamy Sivakumar; Namita Goyal; William S David; Mohammad Salajegheh; Jens Praestgaard; Estelle Lach-Trifilieff; Anne-Ulrike Trendelenburg; Didier Laurent; David J Glass; Ronenn Roubenoff; Brian S Tseng; Steven A Greenberg Journal: Neurology Date: 2014-11-07 Impact factor: 9.910
Authors: Michael G Hanna; Umesh A Badrising; Olivier Benveniste; Thomas E Lloyd; Merrilee Needham; Hector Chinoy; Masashi Aoki; Pedro M Machado; Christina Liang; Katrina A Reardon; Marianne de Visser; Dana P Ascherman; Richard J Barohn; Mazen M Dimachkie; James A L Miller; John T Kissel; Björn Oskarsson; Nanette C Joyce; Peter Van den Bergh; Jonathan Baets; Jan L De Bleecker; Chafic Karam; William S David; Massimiliano Mirabella; Sharon P Nations; Hans H Jung; Elena Pegoraro; Lorenzo Maggi; Carmelo Rodolico; Massimiliano Filosto; Aziz I Shaibani; Kumaraswamy Sivakumar; Namita A Goyal; Madoka Mori-Yoshimura; Satoshi Yamashita; Naoki Suzuki; Masahisa Katsuno; Kenya Murata; Hiroyuki Nodera; Ichizo Nishino; Carla D Romano; Valerie S L Williams; John Vissing; Lixin Zhang Auberson; Min Wu; Ana de Vera; Dimitris A Papanicolaou; Anthony A Amato Journal: Lancet Neurol Date: 2019-09 Impact factor: 44.182
Authors: Fieke M Cox; Maarten J Titulaer; Jacob K Sont; Axel R Wintzen; Jan J G M Verschuuren; Umesh A Badrising Journal: Brain Date: 2011-09-09 Impact factor: 13.501
Authors: Mark A Price; Victoria Barghout; Olivier Benveniste; Lisa Christopher-Stine; Alastair Corbett; Marianne de Visser; David Hilton-Jones; John T Kissel; Thomas E Lloyd; Ingrid E Lundberg; Francis Mastaglia; Tahseen Mozaffar; Merrilee Needham; Jens Schmidt; Kumaraswamy Sivakumar; Carla DeMuro; Brian S Tseng Journal: J Neuromuscul Dis Date: 2016-03-03