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Activin type II receptor blockade for treatment of muscle depletion in COPD: a randomized trial

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Title: Activin type II receptor blockade for treatment of muscle depletion in COPD: a randomized trial
Authors: Polkey, MI
Praestgaard, J
Berwick, A
Franssen, FME
Singh, D
Steiner, MC
Casaburi, R
Tillmann, H-C
Lach-Trifilieff, E
Roubenoff, R
Rooks, DS
Item Type: Journal Article
Abstract: RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators. OBJECTIVES: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with COPD and reduced skeletal muscle mass. METHODS: Sixty-seven COPD patients (mean FEV1 1.05 L [41.6% predicted]; aged 40-80 years; body mass index <20 kg/m2 or appendicular skeletal muscle mass index ≤7.25 [men] and ≤5.67 [women] kg/m2), received two doses of either bimagrumab 30 mg/kg intravenously (n=33) or placebo (n=34) (Weeks 0 and 8) over 24 weeks. MEASUREMENTS AND MAIN RESULTS: We assessed changes in thigh muscle volume (TMV, cm3) as the primary endpoint along with 6-minute walk distance (6MWD, m), safety, and tolerability. Fifty-five (82.1%) patients completed the study. TMV increased by Week 4 and remained increased at Week 24 in bimagrumab-treated patients, whereas no changes were observed with placebo (Week 4: +5.9% [3.4%, SD] vs. 0.0% [3.3%], P<0.001; Week 8: +7.0% [3.7%] vs. -0.7% [2.8%], P<0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P<0.001; Week 24: +5.0% [4.9%] vs. -1.3% [4.3%], P<0.001). Over 24 weeks, 6MWD did not increase significantly in either group. Adverse events in bimagrumab group included muscle-related symptoms, diarrhea, and acne, most of which were mild in severity. CONCLUSIONS: Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01669174.
Issue Date: 10-Aug-2018
Date of Acceptance: 10-Aug-2018
URI: http://hdl.handle.net/10044/1/61970
DOI: https://dx.doi.org/10.1164/rccm.201802-0286OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Copyright Statement: © 2018 American Thoracic Society.
Sponsor/Funder: National Institute for Health Research
Funder's Grant Number: BRU 6279
Keywords: 6-Minute Walk Distance
Bimagrumab
Lean Body Mass
Thigh Muscle Volume
11 Medical And Health Sciences
Respiratory System
Publication Status: Published online
Conference Place: United States
Online Publication Date: 2018-08-10
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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