Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies

Abstract

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.

Autologous hematopoietic stem cell transplantation following alemtuzumab therapy in aggressive multiple sclerosis: A report of three cases

“…Although additional alemtuzumab courses improve outcomes, about one third of the patients continue to have magnetic resonance imaging (MRI) activity despite three or four alemtuzumab courses. 4 Autologous hematopoietic stem cell transplantation (aHSCT) has been demonstrated to abolish disease activity in the majority of treatment-refractory MS patients 5 representing an ideal candidate for managing alemtuzumab-resistant patients. However, there are no reports of the use of aHSCT following treatment with alemtuzumab.…”

Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing–Remitting Multiple Sclerosis Patients? A Narrative Review

“…Indeed, an action on the innate immune system has been described as an important contributor to the efficacy of alemtuzumab [28]. Improved efficacy without additional safety concerns has been found with continuance of the second course of alemtuzumab when relapses occurred after the first course [29] and administration of additional courses of alemtuzumab when RMS disease activity continued after the second course [30].…”

Intensive immunosuppression followed by autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis

“…Additional courses may be given if there is breakthrough disease activity at follow up. 76 Three major adverse events have been recognized: infusion-related reactions, infections, and secondary autoimmune disease, in particular thyroid gland disease.…”