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Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses. Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) studies and their extensions. Methods: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course. Results: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses. Conclusion: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown. [ABSTRACT FROM AUTHOR]

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]

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses., Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif ® Efficacy in Multiple Sclerosis) studies and their extensions., Methods: Subgroups were based on the number of additional alemtuzumab courses received. Exclusion criteria: other disease-modifying therapy (DMT); <12-month follow-up after last alemtuzumab course., Results: In the additional-courses groups, Courses 3 and 4 reduced annualized relapse rate (12 months before: 0.73 and 0.74, respectively; 12 months after: 0.07 and 0.08). For 36 months after Courses 3 and 4, 89% and 92% of patients were free of 6-month confirmed disability worsening, respectively, with 20% and 26% achieving 6-month confirmed disability improvement. Freedom from magnetic resonance imaging (MRI) disease activity increased after Courses 3 and 4 (12 months before: 43% and 53%, respectively; 12 months after: 73% and 74%). Safety was similar across groups; serious events occurred irrespective of the number of courses., Conclusion: Additional alemtuzumab courses significantly improved outcomes, without increased safety risks, in CARE-MS patients with continued disease activity after Course 2. How this compares to outcomes if treatment is switched to another DMT instead remains unknown.

Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)-approved in March 2013. Interestingly, dimethyl fumarate served as the active compound used for the treatment of psoriasis for decades. Alemtuzumab remains under investigation and is not currently FDA-approved for treatment of MS. Other drugs currently approved for alternative indications are being investigated for use in MS. Additionally, an investigation of alternative dosing strategies for glatiramer acetate suggests that patients may benefit from a higher dose formulation and less frequent medication administration. Advances in basic science research have identified another potential autoantigenic target in MS, KIR4.1, which may provide further insight into MS pathophysiology.