Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy

Abstract

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.

Conflict of interest statement

SPS, JP, LC, and SM are employees of and hold stock or stock options in Pfizer. KRW is an employee of and holds stock in F. Hoffmann-La Roche Ltd. HZA-H has received research support from and served on advisory boards for Sarepta Therapeutics, Biogen, NS Pharma, and AveXis/Novartis. CT has been site investigator for clinical trials with Pfizer, AveXis/Novartis, Catabasis, WaVe, Roche, PTC Therapeutics, FibroGen, Capricor, Santhera, Sarepta Therapeutics, and Summit. JKM has received research support for clinical trials from Pfizer, Italfarmaco, Sarepta Therapeutics, Catabasis, Roche, Biogen, Novartis, NS Pharma, PTC Therapeutics, and ReveraGen; and consultant fees from PTC Therapeutics, Roche, and Biogen. FM is a member of the Pfizer Rare Disease Scientific Advisory Board; received grant support from Biogen and Sarepta Therapeutics; and received consultant fees and/or speakers’ honoraria from Novartis, Biogen, Roche, Dyne Therapeutics, and PTC Therapeutics. MG has served as chair for a ReveraGen study; collaborated on research with ReveraGen and Sarepta Therapeutics; acted as principal investigator for clinical trials sponsored by Pfizer, Italfarmaco, Santhera Therapeutics, ReveraGen, Dynacure, Roche, PTC Therapeutics, and Summit; participated in advisory boards for Pfizer, NS Pharma, and Dyne (consultancies through Newcastle University); and performed consultancy work (speaker) for Sarepta Therapeutics. RJB has received funding via contracts for clinical trials from AveXis/Novartis, PTC Therapeutics, Sarepta Therapeutics, Pfizer, and Biogen; and has served on scientific advisory boards for Sarepta Therapeutics, Biogen, AveXis/Novartis, and Pfizer.

© 2022. The Author(s).

Figures

Figure 1

Representative DXA scan. A visual representation of fat mass, lean body mass and bone mass is shown for a participant (a) before treatment and (b) at the Week 49 visit. Cutlines are placed on the DXA scan to separate regions of interest for analysis (c). Primary regions for analysis included arms (left and right combined), legs (left and right combined), appendicular skeleton (arms and leg as a single region of interest) and total body excluding the head. Cutlines were placed by a trained analyst and reviewed by a radiologist prior to finalizing read results. DXA, Dual-energy X-ray absorptiometry.

Figure 2

Change from baseline in DXA lean body mass. Least-squares mean change from baseline in lean body mass at Weeks 17, 33 and 49 for (a) whole body, (b) appendicular skeleton, (c) total legs and (d) total arms; (e) shows percent lean mass. DXA, Dual-energy X-ray absorptiometry.