A 5-year natural history cohort of patients with facioscapulohumeral muscular dystrophy determining disease progression and feasibility of clinical outcome assessments for clinical trials.

Introduction/aims: The number of clinical trials in facioscapulohumeral muscular dystrophy (FSHD) is expected to increase in the near future. There is a need for clinical outcome assessments (COAs) that can capture disease progression over the relatively short time span of a clinical trial. In this study, we report the natural progression of FSHD and determine the feasibility of COAs for clinical trials.

Methods: Genetically confirmed FSHD patients underwent various COAs at baseline and after 5 years. COAs consisted of the Motor Function Measure (MFM), manual muscle testing using the Medical Research Council score, six-minute walk test, quantitative muscle strength assessment of the quadriceps muscle, clinical severity score, and FSHD evaluation score (FES). Statistical significance and the minimal clinically important difference (MCID) were calculated and power calculations were performed.

Results: One hundred fifty-four symptomatic FSHD patients were included, with a mean (SD) age of 51.4 (14.6) years old. All COAs showed a minimal, yet statistically significant progression after 5 years. MCID was reached for the MFM Domain 1, MFM total score, and FES. These three COAs showed the lowest sample size requirements for clinical trials (185, 156, and 201 participants per group, respectively, for a trial duration of 2 years).

Discussion: The captured FSHD disease progression rate in 5 years was generally minimal. The COAs in this study are not feasible for clinical trials with a duration of 2 years. Extended trial durations or novel outcome assessments might be necessary to improve trial feasibility in FSHD.