Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis Long-term Extension of RESILIENT

被引：33

作者：

Amato, Anthony A. ^{[1
,2
]}

Hanna, Michael G. ^{[3
]}

Machado, Pedro M. ^{[3
,4
,5
,6
,7
,8
]}

Badrising, Umesh A. ^{[9
]}

Chinoy, Hector ^{[10
]}

Benveniste, Olivier ^{[11
]}

Karanam, Ananda Krishna ^{[12
]}

Wu, Min ^{[13
]}

Tanko, Laszlo B. ^{[14
]}

Schubert-Tennigkeit, Agnes Annette ^{[14
]}

Papanicolaou, Dimitris A. ^{[13
]}

Lloyd, Thomas E. ^{[15
]}

Needham, Merrilee ^{[16
,17
]}

Liang, Christina ^{[18
]}

Reardon, Katrina A. ^{[12
,19
]}

de Visser, Marianne ^{[20
]}

Ascherman, Dana P. ^{[21
]}

Barohn, Richard J. ^{[22
]}

Dimachkie, Mazen M. ^{[22
]}

Miller, James A. L. ^{[23
]}

Kissel, John T. ^{[24
]}

Oskarsson, Bjorn ^{[25
,59
]}

Joyce, Nanette C. ^{[25
]}

Van den Bergh, Peter ^{[26
]}

Baets, Jonathan ^{[27
,28
]}

De Bleecker, Jan L. ^{[29
]}

Karam, Chafic ^{[30
]}

David, William S. ^{[31
,32
]}

Mirabella, Massimiliano ^{[33
,34
]}

Nations, Sharon P. ^{[35
]}

Jung, Hans H. ^{[36
,37
]}

Pegoraro, Elena ^{[38
]}

Maggi, Lorenzo ^{[39
]}

Rodolico, Carmelo ^{[40
]}

Filosto, Massimiliano ^{[41
,42
]}

Shaibani, Aziz, I ^{[43
]}

Sivakumar, Kumaraswamy ^{[44
]}

Goyal, Namita A. ^{[45
]}

Mori-Yoshimura, Madoka ^{[46
]}

Yamashita, Satoshi ^{[47
]}

Suzuki, Naoki ^{[48
]}

Aoki, Masashi ^{[49
]}

Katsuno, Masahisa ^{[50
]}

Morihata, Hirokazu ^{[51
]}

Murata, Kenya ^{[52
]}

Nodera, Hiroyuki ^{[53
,58
]}

Nishino, Ichizo ^{[54
]}

Romano, Carla D. ^{[55
]}

Williams, Valerie S. L. ^{[55
]}

Vissing, John ^{[56
]}

机构：

[1] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] UCL, Med Res Council Ctr Neuromuscular Dis, London, England

[4] UCL, Inst Neurol, Dept Neuromuscular Dis, London, England

[5] UCL, Ctr Rheumatol, London, England

[6] Univ Coll London Hosp NHS Fdn Trust, Dept Rheumatol, London, England

[7] Univ Coll London Hosp NHS Fdn Trust, Queen Sq Ctr Neuromuscular Dis, London, England

[8] London North West Univ Healthcare NHS Trust, Northwick Pk Hosp, Dept Rheumatol, London, England

[9] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands

[10] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Univ NHS Fdn Trust, Natl Inst Hlth Res,Manchester Biomed Res Ctr, Manchester, Lancs, England

[11] Sorbonne Univ, Pitie Salpetriare Hosp, Dept Internal Med & Clin Immunol, Paris, France

[12] Novartis Healthcare Pvt Ltd, Hyderabad, India

[13] Novartis Pharmaceut, E Hanover, NJ USA

[14] Novartis Pharma AG, Basel, Switzerland

[15] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[16] Murdoch Univ, Fiona Stanley Hosp, Inst Immunol & Infect Dis, Perth, WA, Australia

[17] Notre Dame Univ, Perth, WA, Australia

[18] Royal North Shore Hosp, Dept Neurol, St Leonards, NSW, Australia

[19] Calvary Hlth Care Bethlehem, Caulfield, Australia

[20] Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands

[21] Univ Miami, Dept Med, Coral Gables, FL 33124 USA

[22] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA

[23] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Neurol, Newcastle Upon Tyne, Tyne & Wear, England

[24] Ohio State Univ, Wexner Med Ctr, Dept Neurol, Columbus, OH 43210 USA

[25] UC Davis Sch Med, Neuromuscular Res Ctr, Sacramento, CA USA

[26] Univ Louvain, Univ Hosp St Luc, Dept Neurol, Brussels, Belgium

[27] Antwerp Univ Hosp, Dept Neurol, Neuromuscular Reference Ctr, Antwerp, Belgium

[28] Univ Antwerp, Inst Born Bunge, Antwerp, Belgium

[29] Ghent Univ Hosp, Dept Neurol, Ghent, Belgium

[30] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA

[31] Massachusetts Gen Hosp, Neuromuscular Diagnost Ctr, Dept Neurol, Boston, MA 02114 USA

[32] Electromyog Lab, Boston, MA USA

[33] Fdn Policlin Univ Agostino Gemelli IRCCS, Dept Neurol, Rome, Italy

[34] Univ Cattolica Sacro Cuore, Rome, Italy

[35] Univ Texas Southwestern Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA

[36] Univ Hosp, Dept Neurol, Zurich, Switzerland

[37] Univ Zurich, Zurich, Switzerland

[38] Univ Padua, Dept Neurosci, Sch Med, Padua, Italy

[39] Fdn IRCCS Ist Neurol Carlo Besta, Milan, Italy

[40] Univ Messina, Azienda Osped Univ Policlin G Martino, Unit Neurol & Neuromuscular Disorders, Messina, Italy

[41] ASST Spedali Civili, Unit Neurol, Ctr Neuromuscular Dis, Brescia, Italy

[42] Univ Brescia, Brescia, Italy

[43] Nerve & Muscle Ctr Texas, Houston, TX USA

[44] Neuromuscular Res Ctr, Phoenix, AZ USA

[45] Univ Calif Irvine, Dept Neurol, ALS & Neuromuscular Ctr, Orange, CA 92668 USA

[46] Natl Ctr Hosp, Natl Ctr Neurol & Psychiat, Dept Neurol, Tokyo, Japan

[47] Kumamoto Univ Hosp, Dept Neurol, Kumamoto, Japan

[48] Tohoku Univ Hosp, Dept Neurol, Sendai, Miyagi, Japan

[49] Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi, Japan

[50] Nagoya Univ Hosp, Dept Neurol, Nagoya, Aichi, Japan

来源：

NEUROLOGY | 2021年 / 96卷 / 12期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1212/WNL.0000000000011626

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

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. Classification of Evidence This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, welltolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.

引用

页码：E1595 / E1607

页数：13

共 16 条

[1]

Inclusion body myositis: therapeutic approaches [J].

Aggarwal, Rohit ;

Oddis, Chester V. .

DEGENERATIVE NEUROLOGICAL AND NEUROMUSCULAR DISEASE, 2012, 2 :43-52

[2]

Treatment of sporadic inclusion body myositis with bimagrumab [J].

Amato, Anthony A. ;

Sivakumar, Kumaraswamy ;

Goyal, Namita ;

David, William S. ;

Salajegheh, Mohammad ;

Praestgaard, Jens ;

Lach-Trifilieff, Estelle ;

Trendelenburg, Anne-Ulrike ;

Laurent, Didier ;

Glass, David J. ;

Roubenoff, Ronenn ;

Tseng, Brian S. ;

Greenberg, Steven A. .

NEUROLOGY, 2014, 83 (24) :2239-2246

[3]

Long-term observational study of sporadic inclusion body myositis [J].

Benveniste, Olivier ;

Guiguet, Marguerite ;

Freebody, Jane ;

Dubourg, Odile ;

Squier, Waney ;

Maisonobe, Thierry ;

Stojkovic, Tanya ;

Leite, Maria Isabel ;

Allenbach, Yves ;

Herson, Serge ;

Brady, Stefen ;

Eymard, Bruno ;

Hilton-Jones, David .

BRAIN, 2011, 134 :3176-3184

[4]

A 12-year follow-up in sporadic inclusion body myositis: an end stage with major disabilities [J].

Cox, Fieke M. ;

Titulaer, Maarten J. ;

Sont, Jacob K. ;

Wintzen, Axel R. ;

Verschuuren, Jan J. G. M. ;

Badrising, Umesh A. .

BRAIN, 2011, 134 :3167-3175

[5]

DEVELOPMENT OF THE SPORADIC INCLUSION BODY MYOSITIS PHYSICAL FUNCTIONING ASSESSMENT [J].

Demuro, Carla ;

Lewis, Sandy ;

Lowes, Linda ;

Alfano, Lindsay ;

Tseng, Brian ;

Gnanasakthy, Ari .

MUSCLE & NERVE, 2016, 54 (04) :653-657

[6]

Inclusion Body Myositis [J].

Dimachkie, Mazen M. ;

Barohn, Richard J. .

NEUROLOGIC CLINICS, 2014, 32 (03) :629-+

[7]

Sporadic inclusion-body myositis: Recent advances and the state of the art in 2016 [J].

Gallay, L. ;

Petiot, P. .

REVUE NEUROLOGIQUE, 2016, 172 (10) :581-586

[8]

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial [J].

Hanna, Michael G. ;

Badrising, Umesh A. ;

Benveniste, Olivier ;

Lloyd, Thomas E. ;

Needham, Merrilee ;

Chinoy, Hector ;

Aoki, Masashi ;

Machado, Pedro M. ;

Liang, Christina ;

Reardon, Katrina A. ;

de Visser, Marianne ;

Ascherman, Dana P. ;

Barohn, Richard J. ;

Dimachkie, Mazen M. ;

Miller, James A. L. ;

Kissel, John T. ;

Oskarsson, Bjoern ;

Joyce, Nanette C. ;

Van den Bergh, Peter ;

Baets, Jonathan ;

De Bleecker, Jan L. ;

Karam, Chafic ;

David, William S. ;

Mirabella, Massimiliano ;

Nations, Sharon P. ;

Jung, Hans H. ;

Pegoraro, Elena ;

Maggi, Lorenzo ;

Rodolico, Carmelo ;

Filosto, Massimiliano ;

Shaibani, Aziz, I ;

Sivakumar, Kumaraswamy ;

Goyal, Namita A. ;

Mori-Yoshimura, Madoka ;

Yamashita, Satoshi ;

Suzuki, Naoki ;

Katsuno, Masahisa ;

Murata, Kenya ;

Nodera, Hiroyuki ;

Romano, Carla D. ;

Williams, Valerie S. L. ;

Vissing, John ;

Auberson, Lixin Zhang ;

Wu, Min ;

de Vera, Ana ;

Papanicolaou, Dimitris A. ;

Amato, Anthony A. ;

Nishino, Ichizo .

LANCET NEUROLOGY, 2019, 18 (09) :834-844

[9]

Hilton-Jones D, 2010, NEUROMUSCULAR DISORD, V20, P622, DOI [10.1016/j.nmd.2010.07.087, 10.1016/j.nmd.2009.11.003]

[10]

Update on sporadic inclusion body myositis [J].

Hohlfeld, Reinhard .

BRAIN, 2011, 134 :3141-3145

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