P.93 Effect of rapamycine on quantitative MRI outcome measures in inclusion body myositis

Abstract

Quantitative magnetic resonance imaging (qMRI) outcome measures such as muscle fat fraction (FF) and contractile cross-sectional area (cCSA), reflecting disease progression, and water T2, reflecting disease activity (inflammation, edema), are used in the longitudinal studies of neuromuscular diseases, including inclusion body myositis (IBM). Here, we report qMRI results from the RAPAMI study (NCT02481453), obtained at 3 Tesla in the muscle of 45 patients (rapamycine vs. placebo) at baseline and year-1. Values for FF, cCSA and water T2 values were calculated in anterior and posterior (triceps surae) leg and anterior (quadriceps) and posterior (hamstring) thigh muscle groups. Functional assessments included the six-minute walking distance (6MWD). Student's t-tests and Pearson correlation analyses were performed (P<0.05). Standardized response means (SRM) values were calculated to assess the sensitivity to change for the different MRI outcome measures. No differences in demographic data existed between rapamycine and placebo groups (P>0.20). Overall, patients (20 female, 23 male) were 66±8 years old and had symptoms for 8±5 years. There was a significant left-right difference for FF and cCSA (P<0.001) but not for water T2 (P=0.89). Values of FF and cCSA at baseline were not significantly different between both patient groups for anterior and posterior leg and thigh muscle groups (P>0.11). FF increase after one year was significantly lower in the rapamycine group for the posterior (P<0.027) but not for the anterior muscle group (P>0.08). The one-year decrease in anterior thigh cCSA was slightly significantly higher in the placebo group (P=0.045). The SRM values for FF and cCSA changes were systematically higher in the placebo group with SRM>0.8 for FF in triceps surae and quadriceps and SRM>0.8 for cCSA in hamstring, only in the rapamycine group. Water T2 was significantly elevated in leg and anterior thigh muscle compared to control values (≈39ms) and a moderately strong relation between baseline water T2 and the FF change was observed in posterior thigh (R2=0.57, overall patients). The increase in anterior thigh FF associated with a decrease in 6MWD was particularly observed in the placebo group (R2=0.30). qMRI has demonstrated that small yet significant changes can be measured between non-treated and treated IBM patients, within specific muscle groups, and correlates to function measures.