title: 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.
abstract: 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.
authors.affiliation: Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. sarudnicki@uams.edu
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Rudnicki
authors.forename: James D
authors.initials: JD
authors.lastname: Berry
authors.forename: Evan
authors.initials: E
authors.lastname: Ingersoll
authors.forename: Don
authors.initials: D
authors.lastname: Archibald
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kerr
authors.forename: Yingwen
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality*; D052160:Benzothiazoles / Q000008:administration & dosage*; D018491:Dopamine Agonists / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D015995:Prevalence; D020127:Recovery of Function / Q000187:drug effects*; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D000077487:Pramipexole