Alemtuzumab – Does Age Matter? Or Not?

Alemtuzumab in the Treatment of MS

Although it is undoubtedly an important topic, the influence of age on the efficacy and safety of disease-modifying drugs (DMDs) receives little attention. This is why the authors of the cited study focused on one of the highly effective DMDs – alemtuzumab – and its efficacy and safety across different age categories.

Alemtuzumab is a humanized monoclonal antibody used in the treatment of relapsing-remitting MS. It is indicated for patients with highly active disease despite treatment with at least one other DMD or in cases of rapidly evolving MS.

The surface glycoprotein CD52, targeted by alemtuzumab, is primarily present on T (CD3⁺) and B (CD19⁺) lymphocytes. Alemtuzumab acts through antibody-dependent cellular cytolysis and complement-mediated lysis following binding to T and B lymphocyte surfaces. By depleting and repopulating lymphocytes, it ultimately delays disease progression.

Results of the post hoc Analysis

The study evaluated the efficacy and safety of alemtuzumab across different age groups over an 8-year follow-up period. Patients (n = 811) assessed in this post hoc analysis of the CARE-MS clinical study data were divided into the following age categories: 18–25 years (n = 137), 25–35 years (n = 350), 35–45 years (n = 238), and 45–55 years (n = 86).

Compared to subcutaneous interferon beta-1a, the annual relapse rate after 2 years was significantly lower in patients on alemtuzumab therapy (0.22–0.24 vs. 0.38–0.51). Similarly, patients on alemtuzumab therapy achieved better outcomes in terms of disability progression, new lesions on brain MRI, and brain atrophy. No significant differences in the efficacy of alemtuzumab therapy were observed across the different age categories over the 2-year period.

Alemtuzumab was associated with favorable outcomes even after 8 years of follow-up, irrespective of age. However, the number of adverse events increased with age. The incidence of malignancies was 0.9–2.2% in the under-45 age group compared to 8.1% in older patients. Higher mortality was also observed in older age groups (0–1.7% vs. 7%). The incidence of serious infections increased with age as well (5.1% vs. 12.8%).

Conclusion

As expected, the incidence of adverse events increased with age in patients on alemtuzumab therapy. However, the positive news is the proven efficacy of alemtuzumab in both the 2nd and 8th years of follow-up, regardless of patient age. Compared to interferon beta-1a, alemtuzumab was more effective in terms of relapse rate, disability progression, and MRI-documented brain changes over the observed period.

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Source: Bass A. D., Arroyo R., Boster A. L. et al. Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years. Mult Scler Relat Disord 2021 Apr; 49: 102717, doi: 10.1016/j.msard.2020.102717.