G.O.18 - Patterns of disease progression in type 2 and 3 SMA: Implications for clinical trials

Abstract

This observational study provides the largest dataset of longitudinal data reported so far in patients with type 2 and 3 SMA. The aim of the study was to establish 12-month changes in the Hammersmith Functional motor scale expanded in a large cohort of ambulant and non-ambulant SMA patients, to identify patterns of disease progression and the possible effect of different variables, such as gender, baseline values or age. 268 patients were included in the study. Their age ranged from 2.5 to 55.5 years at baseline, 68 were ambulant and 200 non-ambulant. The baseline scores ranged from 0 to 66 (mean 23.91, SD 20.09). The 12-month change was between −14 and +9 (mean −0.56, SD 2.72). Of the 268 patients, 206 (76.86%) had changes between −2 and +2 points. Ambulant and non-ambulant subjects had a different relationship between baseline values and age (p for age X ambulation interaction = 0.007). There was no association with age in ambulant subjects, while there was a significant heterogeneity at different age levels for non-ambulant patients (p < 0.001). The 12-month change (adjusted for baseline) was not associated with age in ambulant patients (p = 0.34), but it was significantly different among various age groups in non-ambulant patients. Our results suggest that there are different profiles of progression in ambulant and non-ambulant patients, and that age may play an important role in the progression of non-ambulant patients. These findings will be of help when deciding inclusion and stratification criteria for clinical trials.