In this article, we will discuss Alemtuzumab (Mechanism of Action). So, let’s get started.
Mechanism of Action
The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes, and macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab results in antibody-dependent cellular cytolysis and complement-mediated lysis.
Effects of alemtuzumab on the Lymphocyte Population
Alemtuzumab depletes circulating T and B lymphocytes after each treatment course. In clinical trials, the lowest cell counts occurred 1 month after a course of treatment at the time of the first post-treatment blood count. Lymphocyte counts then increased over time: B cell counts usually recovered within 6 months; T cell counts increased more slowly and usually remained below baseline 12 months after treatment. Approximately 60% of patients had total lymphocyte counts
below the lower limit of normal 6 months after each treatment course and 20% had counts below the lower limit of normal after 12 months. Reconstitution of the lymphocyte population varies for the different lymphocyte subtypes. At Month 1 in clinical trials, the mean CD4+ lymphocyte count was 40 cells per microliter, and, at Month 12, 270 cells per microliter. At 30 months, approximately half of patients had CD4+ lymphocyte counts that remained below the lower limit of normal.
In a study of 53 MS patients, alemtuzumab 12 mg per day for 5 days caused no changes in the QTc interval greater than 20 ms. An average 22 to 26 beats-per-minute increase in heart rate was observed for at least 2 hours after the first but not subsequent infusions.