(DXT65) Longitudinal Disability Follow-up in Patients with 6-Month Confirmed Disability Improvement or Worsening in the CARE-MS and Extension Studies.

Background: In the 2-year CARE-MS trials (trial registration: NCT00530348; NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/magnetic resonance imaging outcomes vs subcutaneous interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS). Efficacy in alemtuzumab-treated patients was maintained through year 9 in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). Objectives: To evaluate the status of disability over 9 years in pooled CARE-MS patients who had either 6-month confirmed disability improvement (CDI) or 6-month confirmed disability worsening (CDW) by years 2 or 9. Methods: Alemtuzumab-treated CARE-MS patients with baseline Expanded Disability Status Scale (EDSS) score ≥2 were stratified into 3 subgroups: with CDI, with CDW, or with stable disability. CDI and CDW were defined as ≥1-point decrease and increase, respectively, in EDSS score from core study baseline confirmed over 6 months. Improved and stable EDSS scores each year were defined as ≥1-point decrease and ≤0.5-point change in either direction, respectively, from core study baseline in available patients. Results: 511/811 (63%) alemtuzumab-treated patients had baseline EDSS score ≥2. Of these, 222 (43%) patients had 365 unique CDI events and 172 (34%) patients had 217 CDW events at any time during the 9-year study; 31 (6%) had both CDI and CDW. Few patients (n = 12) had a CDW event after CDI. Of patients with CDI at any time over 9 years, mean EDSS score change was --0.58 at year 9 vs core study baseline, and 51% had lower EDSS scores at year 9. Similar EDSS outcomes were observed at year 9 in the subset of patients who achieved CDI within the first 2 years of the study. However, patients with CDW any time over 9 years had worsened disability at year 9, with a +1.71 mean change in EDSS score from core study baseline; patients with CDW in the first 2 years of the study had a +2.27 EDSS score change by year 9. EDSS scores remained stable at 9 years (mean change, --0.10) in the 148 (29%) patients who had neither CDI nor CDW. Compared with previous years, no new safety signals were identified in year 9 in CARE-MS extension study patients. Conclusions: Achievement of CDI at any point in the CARE-MS studies was associated with improved disability at year 9 vs baseline. However, those with CDW had increased disability over 9 years regardless of when worsening occurred. These findings suggest that both CDI and CDW are meaningful end points for predicting long-term disability outcomes in patients with RRMS. [ABSTRACT FROM AUTHOR]