Effect of sirolimus on muscle in inclusion myositis observed by MRI and spectroscopy

Harmen Reyngoudt is co-director of the Institute’s NMR imaging and spectroscopy laboratory. He has just published an article* in J Cachexia Sarcopenia Muscle on the effect of sirolimus on muscle assessed by magnetic resonance imaging and spectroscopy. Interview with Harmen Reyngoudt.

What is the background to this work?

In order to make progress in clinical research, whether it be establishing the natural history of diseases or measuring the effects in therapeutic trials, it is essential to find reproducible and sufficiently sensitive assessment methods for neuromuscular diseases.

What was the aim of this study?

In this one-year, placebo-controlled study of sirolimus for inclusion body myositis (IBM), we focused on longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS). In 2021, we had already reported a minimum of relevant MRI results in the paper published by Benveniste et al**. In parallel, we examined functional, strength and clinical parameters in the muscles of the lower limbs.

How did you go about this?

We collected 31P MRI and MRS data at 3T from 44 patients (22 on placebo, 22 on sirolimus) at baseline and year one, and 21 healthy controls.

Fat fraction (FF), contractile cross-sectional area (cCSA) and T2 water in the overall leg and thigh segments, muscle groups, individual muscles, and 31P MRS indices in the quadriceps or triceps surae were assessed.

Analyses included patient-control comparisons, assessments of annual changes using statistical tests, functional parameters, strength parameters and clinical parameters.

What results did you obtain and what conclusions did you draw?

We observed, for example, that the differences in changes in FF and cCSA between the two groups of patients were significant. Or that there were significant correlations between FF, cCSA, water T2, and measures of functional results and strength.

This work demonstrates that quantitative/31P MRS can discern measurable differences between placebo-treated and sirolimus-treated IMB patients, which is promising for future therapeutic trials in idiopathic inflammatory myopathies such as IMB.

 

* Reyngoudt H, Baudin PY, de Caldas de Almeida Araújo E, Bachasson D, Boisserie JM, Mariampillai K, Annoussamy M, Allenbach Y, Hogrel JY, Carlier PG, Marty B, Benveniste O. Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy. J Cachexia Sarcopenia Muscle. 2024;15(3):1108-1120. doi: 10.1002/jcsm.13451.

 

** Benveniste O, Hogrel JY, Belin L, Annoussamy M, Bachasson D, Rigolet A, Laforet P, Dzangué-Tchoupou G, Salem JE, Nguyen LS, Stojkovic T, Zahr N, Hervier B, Landon-Cardinal O, Behin A, Guilloux E, Reyngoudt H, Amelin D, Uruha A, Mariampillai K, Marty B, Eymard B, Hulot JS, Greenberg SA, Carlier PG, Allenbach Y. Sirolimus for treatment of patients with inclusion body myositis: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2b trial. Lancet Rheumatol 2021;3(1):e40-e48. doi: 10.1016/S2665-9913(20)30280-0.