Berkovich, Regina, Alroughani, Raed, Bass, Ann D., Boster, Aaron L., Comi, Giancarlo, Ho Jin Kim, Limmroth, Volker, Lycke, Jan, Macdonell, Richard A. L., Schippling, Sven, Sharrack, Basil, Tintoré, Mar, Traboulsee, Anthony, Vermersch, Patrick, Wiendl, Heinz, Ziemssen, Tjalf, Daizadeh, Nadia, Jacobs, Alan, Poole, Elizabeth M., and Singer, Barry A.
Background: In CARE-MS I and II (trial registration: NCT00530348, NCT00548405), alemtuzumab treatment (12 mg/day; baseline: 5 days; 12 months later: 3 days) improved clinical and magnetic resonance imaging (MRI) outcomes vs subcutaneous interferon beta-1a over 2 years in patients with relapsing-remitting multiple sclerosis (MS). In 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]), patients could receive additional alemtuzumab (12 mg/day; 3 days; ≥12 months apart). Objectives: Evaluate yearly efficacy and safety of alemtuzumab in pooled CARE-MS patients who did or did not receive additional alemtuzumab through year 9. Methods: Pooled CARE-MS patients were stratified by the total number of courses received (exactly 2 courses, exactly 3 courses, ≥4 courses). Inclusion criteria: additional alemtuzumab (ie, courses 3 or 4) received by month 97 to allow ≥12 months of follow-up; no other disease-modifying therapy through year 9. Data were censored at course 5 (if received) in the ≥4 courses group. Outcomes data were rebaselined after the last alemtuzumab course. Results: 742/811 (91%) alemtuzumab-treated patients entered the extension and could receive additional courses; courses 3 and 4 were given most frequently in years 3 (19%) and 4 (6%), respectively. Of 742 extension patients, 359 (48%), 148 (20%), and 121 (16%) were included in the 2-, 3-, and ≥4-courses groups, with 303, 76, and 15 remaining on study in year 4 after last course, respectively. Over 4 years after last course, annualized relapse rate was 0.07, 0.08, and 0.23 in the 2-, 3-, and ≥4-courses groups, respectively, and change in mean Expanded Disability Status Scale score at year 4 vs after last course was -0.06, +0.08, and +0.56, respectively. Over 4 years, 83%, 85%, and 94% were free of 6-month confirmed disability worsening, and 23%, 11%, and 15% had 6-month confirmed disability improvement in the 2-, 3-, and ≥4-courses groups, respectively. In year 4, 78%, 73%, and 69% were free of MRI disease activity. Serious adverse events were generally similar between cohorts during years 1-3 after last treatment (5.1%-11.4% per year), but low patient numbers in the ≥4-courses group confounded analysis of serious adverse events in year 4 after last course. Conclusions: Efficacy of additional alemtuzumab was maintained over 4 years after last course in CARE-MS patients, although the ≥4-courses group had higher disease activity and disability, as expected. Alemtuzumab safety was generally consistent between groups, except for the ≥4-courses cohort in year 4 after last course wherein interpretation was limited by low numbers of available patients. [ABSTRACT FROM AUTHOR]