Orphazyme (Denmark)

ObjectivesTo evaluate the validity, reliability, responsiveness and meaningful change threshold of the Inclusion Body Myositis (IBM) Functional Rating Scale (FRS).MethodsData from a large 20-month multicentre, randomised, double-blind, placebo-controlled trial in IBM were used. Convergent validity was tested using Spearman correlation with other health outcomes. Discriminant (known groups) validity was assessed using standardised effect sizes (SES). Internal consistency was tested using Cronbach’s alpha. Intrarater reliability in stable patients and equivalence of face-to-face and telephone administration were tested using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Responsiveness was assessed using a standardised response mean (SRM). An receiver operator characteristic (ROC) curve anchor-based approach was used to determine clinically meaningful IBMFRS change.ResultsAmong the 150 patients, mean (SD) IBMFRS total score was 27.4 (4.6). Convergent validity was supported by medium to large correlations (rs modulus: 0.42–0.79) and discriminant validity by moderate to large group differences (SES=0.51–1.59). Internal consistency was adequate (overall Cronbach’s alpha: 0.79). Test–retest reliability (ICCs=0.84–0.87) and reliability of telephone versus face-to-face administration (ICCs=0.93–0.95) were excellent, with Bland-Altman plots showing good agreement. Responsiveness in the worsened group defined by various external constructs was large at both 12 (SRM=−0.76 to −1.49) and 20 months (SRM=−1.12 to −1.57). In ROC curve analysis, a drop in two IBMFRS total score points was shown to represent a meaningful decline.ConclusionsWhen administered by trained raters, the IBMFRS is a reliable, valid and responsive tool that can be used to evaluate the impact of IBM and its treatment on physical function, with a 2-point reduction representing meaningful decline.Trial registration numberNCT02753530.

To present efficacy and safety/tolerability data from phase 2/3 randomized controlled trial of arimoclomol in IBM (NCT02753530).