Spinal Muscular Atrophy Functional Composite Score Revised (SMA-FCR) in Untreated and Nusinersen-Treated Patient Cohorts.

Background And Objectives: The Spinal Muscular Atrophy Functional Composite (SMA-FC) combines scores from the Hammersmith Functional Motor Scale Expanded (HFMSE), Upper Limb Module (ULM), and Six-Minute Walk Test (6MWT) into a single score and removes the floor and ceiling effects of the HFMSE. Our objective was to evaluate a revised version of the SMA-FC (SMA-FCR) by including the Revised ULM (RULM) in untreated and nusinersen-treated SMA.

Methods: We included participants with HFMSE, RULM, and 6MWT data at the same visit. The SMA-FCR represented the average of the 3 test scores, each expressed as the percentage of the maximum possible score (HFMSE and RULM) or the percent of predicted normative performance (6MWT). Mean annual rates of change were calculated in participants who had SMA-FCR data at 2 or more visits while untreated and/or while treated.

Results: There were 580 participants (49.6% female) with a mean (SD) age of 19.2 (15.5) years (range 1.3-70.6 years). The median (interquartile range) SMA-FCR scores were 3.6 (0.0-8.1) for nonsitters, 22.3 (16.3-31.2) for sitters, and 75.1 (63.7-86.6) for walkers. The SMA-FCR score reduced the ceiling effect seen with the RULM in walkers and the floor effect seen with the HFMSE in nonsitters. The mean annual rate of change in the SMA-FCR was -0.62 (95% CI -1.15 to -0.08, = 0.02) in untreated participants and 0.15 (95% CI -0.12 to 0.42, = 0.28) in treated participants (difference = 0.77, 95% CI 0.19-1.34, = 0.009). The mean annual rate of change in the HFMSE was -0.19 (95% CI -0.63 to 0.25, = 0.40) in untreated participants and -0.21 (95% CI -0.43 to 0.01, = 0.06) in treated participants (difference = -0.02, 95% CI -0.49 to 0.46, = 0.94).

Discussion: The SMA-FCR broadens the spectrum of abilities captured in SMA. Analyses of the treated-untreated differences in mean annual rate of change suggest that the SMA-FCR may be more sensitive to change than the HFMSE. The use of the SMA-FCR in clinical trials might allow for study designs with broader eligibility criteria including weaker individuals who score minimally on the HFMSE and stronger individuals who score maximally on the RULM.