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Effect of sirolimus on muscle in inclusion body myositis observed with magnetic resonance imaging and spectroscopy.

👤 Authors: Harmen Reyngoudt, Pierre-Yves Baudin, Ericky de Caldas de Almeida Araújo, Damien Bachasson, Jean-Marc Boisserie, Kubéraka Mariampillai, Mélanie Annoussamy, Yves Allenbach, Jean-Yves Hogrel, Pierre G Carlier, Benjamin Marty, Olivier Benveniste


Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1-year longitudinal data from quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (P MRS) in a placebo-controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.

Quantitative MRI and P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year-1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross-sectional area (cCSA), and water T in global leg and thigh segments, muscle groups, individual muscles, as well as P MRS indices in quadriceps or triceps surae.

Analyses covered patient-control comparisons, annual change assessments via standard t-tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, P MRS, functional, strength, and clinical parameters. The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps.

In the placebo group, the median 1-year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group.

Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively.

Water T values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T increased significantly only in the sirolimus group's quadriceps (P < 0.01).

Multiple P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T and FF at baseline and the change in FF (P < 0.001).

Additionally, significant correlations were observed between FF, cCSA, water T, and functional and strength outcome measures. This study has demonstrated that quantitative MRI/P MRS can discern measurable differences between placebo and sirolimus-treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.

Harmen Reyngoudt

Medical Imaging

Institute of Myology



ScienceLeadR Reputation
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Muscular Diseases
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