FP.04 Three-year natural history study in Becker muscular dystrophy in The Netherlands

The slow and highly variable disease progression observed in BMD stresses the need to develop outcome measures for clinical trials. We evaluated the responsiveness of different assessments in a cohort of adult BMD patients followed for 3 years. We included 36 genetically confirmed BMD patients (median age at baseline 42.3 years, range 18.6-67.3) of whom 28 were ambulant at baseline (78%). We conducted ambulatory assessments (6WMT, NSAA, 10-meter walk velocity (TMWv), time to rise from floor velocity (TRFv)), PUL1.2 and bilateral maximal voluntary isometric contraction (grip, knee/hip/elbow flexion and extension). The median change and the standard response mean (SRM) at 1- and 3-year follow-up were calculated. Sample sizes (SS) were calculated assuming 50% reduction in disease progression over a 3 year clinical trial with 1:1 randomization. We observed a large variability across all measures, for example the median at baseline for the 6MWT was 439.10m (range 84.30 to 650.00), median change at 1 year follow-up -8.15 (-151.90 to 182.22) and at 3-years -14.50(-151.90 to 158.72). After 1-year follow-up, the SRM was below 0.8 for all considered outcomes. At 3-year follow-up, TMWv and TRFv showed a responsiveness with SRM above 0.8 (1.91, SS 17 and -0.90, SS 79 respectively). Three strength measurements showed SRM >0.8: right elbow flexion (SRM = -1.01, SS 62), left elbow flexion (SRM = -0.85, SS 88) and left hip flexion (SRM = -0.81, SS 96). Of the 29 patients who completed the PUL1.2 at 3rd year follow-up visit, 20 (69%) obtained the maximum score of 74 points. Only one patient lost ambulation during the study. BMD is hallmarked by large inter-individual variability at baseline and follow-up. A relatively stable disease course is common even with 3 years. The ceiling effect of the PUL1.2 illustrates the need for adequate outcome measures in non-ambulant patients. The slow and highly variable disease progression observed in BMD stresses the need to develop outcome measures for clinical trials. We evaluated the responsiveness of different assessments in a cohort of adult BMD patients followed for 3 years. We included 36 genetically confirmed BMD patients (median age at baseline 42.3 years, range 18.6-67.3) of whom 28 were ambulant at baseline (78%). We conducted ambulatory assessments (6WMT, NSAA, 10-meter walk velocity (TMWv), time to rise from floor velocity (TRFv)), PUL1.2 and bilateral maximal voluntary isometric contraction (grip, knee/hip/elbow flexion and extension). The median change and the standard response mean (SRM) at 1- and 3-year follow-up were calculated. Sample sizes (SS) were calculated assuming 50% reduction in disease progression over a 3 year clinical trial with 1:1 randomization. We observed a large variability across all measures, for example the median at baseline for the 6MWT was 439.10m (range 84.30 to 650.00), median change at 1 year follow-up -8.15 (-151.90 to 182.22) and at 3-years -14.50(-151.90 to 158.72). After 1-year follow-up, the SRM was below 0.8 for all considered outcomes. At 3-year follow-up, TMWv and TRFv showed a responsiveness with SRM above 0.8 (1.91, SS 17 and -0.90, SS 79 respectively). Three strength measurements showed SRM >0.8: right elbow flexion (SRM = -1.01, SS 62), left elbow flexion (SRM = -0.85, SS 88) and left hip flexion (SRM = -0.81, SS 96). Of the 29 patients who completed the PUL1.2 at 3rd year follow-up visit, 20 (69%) obtained the maximum score of 74 points. Only one patient lost ambulation during the study. BMD is hallmarked by large inter-individual variability at baseline and follow-up. A relatively stable disease course is common even with 3 years. The ceiling effect of the PUL1.2 illustrates the need for adequate outcome measures in non-ambulant patients.