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Quantitative muscle magnetic resonance imaging as a biomarker for inclusion body myositis in clinical trials: exploring the in vivo effects of arimoclomol
S. Salam1, J.M. Morrow2, M.P. Mcdermott3, N. Zafeiropoulos4, J.S. Thornton5, S. Shah6, S. Wastling7, T.Y. Yousry8, R.J. Barohn9, M.G. Hanna10, M.M. Dimachkie11, P.M. Machado12
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, UK.
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, UK.
- Department of Biostatistics and Computational Biology, University of Rochester Medical Centre, Rochester, NY, USA.
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, UK.
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, UK.
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, UK.
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, UK.
- Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, UK.
- Department of Neurology, University of Missouri, Columbia, MO, USA.
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, UK.
- Neuromuscular Medicine Division, Department of Neurology, University of Kansas Medical Centre, Kansas City, KS, USA.
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London; and NIHR University College London Hospitals, Biomedical Research Centre, London, UK. p.machado@ucl.ac.uk
CER18573
2025 Vol.43, N°2
PI 0334, PF 0344
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PMID: 40018748 [PubMed]
Received: 25/01/2025
Accepted : 11/02/2025
In Press: 26/02/2025
Published: 26/02/2025
Abstract
OBJECTIVES:
To investigate the intramuscular effects of arimoclomol using quantitative magnetic resonance imaging (qMRI) of the thighs in a subset of inclusion body myositis (IBM) participants from a multicentre, randomised, double-blind, placebo-controlled trial, and to further evaluate the utility of qMRI assessments as outcome measures.
METHODS:
Eighteen participants (10 placebo, 8 arimoclomol-treated) were recruited to undergo an MRI at baseline, 12 and 20 months. Spearman correlations between baseline clinical measures and qMRI measurements [fat fraction (FF), remaining muscle area (RMA), magnetisation transfer ratio (MTR), muscle water T2 (T2m) and fat fraction apparent (FFa)] were used to evaluate construct validity. A mixed model repeated measures (MMRM) strategy was employed to estimate mean changes, in order to determine treatment effects on qMRI biomarkers and evaluate responsiveness to disease progression over time. Longitudinal analyses examined Spearman correlations between changes in qMRI and changes in clinical assessments at the last available follow-up.
RESULTS:
Baseline FF, RMA, MTR and FFa of the thigh and quadriceps demonstrated strong construct validity. No significant treatment effects on the qMRI measures were detected. FF, RMA and FFa demonstrated strong responsiveness to disease progression (standardised response means>0.8, p<0.05) at 20 months. Longitudinal changes in thigh T2m were strongly correlated with changes in myometry and modified timed up and go velocity.
CONCLUSIONS:
Arimoclomol had no significant effects on the qMRI measurements evaluated, consistent with clinical outcomes from the main trial. The qMRI measurements demonstrated both validity and responsiveness, further supporting their potential utility as biomarkers in IBM.
