Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

Abstract

Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.

Aggressive multiple sclerosis: a single‐centre, real‐world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab

“…Although additional alemtuzumab courses seem to improve outcomes [20], it was decided to switch our alemtuzumab‐refractory patients to ocrelizumab because of the presence of B‐cell‐mediated secondary autoimmune disorders, the occurrence of concomitant subtle disability progression and/or the occurrence of inflammatory disease activity after both alemtuzumab courses. Although data from clinical trials suggest that patients with early relapses after the first alemtuzumab course still benefit from re‐treatment [21], no such beneficial effect was observed in our alemtuzumab‐treated patients. Accordingly, the risk of MRI inflammatory activity remained significantly higher for alemtuzumab‐treated patients compared to transplanted ones even after a 12‐month MRI re‐baseline.…”

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

“…The results show durable efficacy through five years in the absence of continuous treatment [33]. A 2019 study [34] evaluated the six-year outcomes in patients who relapsed between alemtuzumab courses 1 and 2, i.e., the "early relapsers". The results show the outcome of the "early relapsers" improved after completing the second alemtuzumab course, supporting the fact that administering the approved two-course regimen should maximize the clinical benefit [34].…”

“…A 2019 study [34] evaluated the six-year outcomes in patients who relapsed between alemtuzumab courses 1 and 2, i.e., the "early relapsers". The results show the outcome of the "early relapsers" improved after completing the second alemtuzumab course, supporting the fact that administering the approved two-course regimen should maximize the clinical benefit [34]. A 2019 study [35] shows that quality of life of patients treated with alemtuzumab ameliorates over a six year post-alemtuzumab treatment period, regardless the independently the occurrence of autoimmune thyroid adverse events.…”

Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era

“…This observation supports the hypothesis that administering two-course treatment is more efficient. 46 …”