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Dexpramipexole effects on functional decline and survival in subjects with amyotrophic lateral sclerosis in a Phase II study: Subgroup analysis of demographic and clinical characteristics

2012; Taylor & Francis; Volume: 14; Issue: 1 Linguagem: Inglês

10.3109/17482968.2012.723723

2167-9223

Stacy A. Rudnicki, James Berry, Evan W. Ingersoll, Д. Арчибалд, Merit Cudkowicz, Douglas A. Kerr, Yingwen Dong,

Cholinesterase and Neurodegenerative Diseases

Our objective was to explore treatment effects in patient subgroups using post hoc analyses of data from part 2 of the dexpramipexole Phase II study. Subjects with amyotrophic lateral sclerosis (ALS) received dexpramipexole 300 mg/day or 50 mg/day for 24 weeks. Treatment effects on the slope of the revised ALS Functional Rating Score (ALSFRS-R) and Combined Assessment of Function and Survival (CAFS) were evaluated in dichotomized subgroups: riluzole use, gender, site of symptom onset. Other subgroups were dichotomized using median baseline values for age, ALSFRS-R, slow vital capacity, symptom duration, diagnostic delay, and progression rate. Results showed that there was a 21% reduction in ALSFRS-R decline favoring the 300-mg vs. 50-mg arm (p = 0.177); mean CAFS ranking was significantly higher in the 300-mg vs. 50-mg arm (52.4 vs. 41.1; p = 0.046). Trends were recapitulated in virtually all subgroups. Generally, ALSFRS-R decline was reduced and CAFS rankings were higher in the 300-mg vs. 50-mg arm across subgroups. CAFS rankings were significantly higher in the 300-mg vs. 50-mg arm among subjects with ALSFRS-R scores ≤35, symptom duration <18.7 months, or progression rate ≥ 0.7 points/month (p < 0.03). In conclusion, the observed benefit of 300- vs. 50-mg dexpramipexole on functional decline and survival was generally consistent among subjects regardless of baseline characteristics.