Abstract
Alemtuzumab is a humanized mononclonal antibody known to cause rapid depletion of B-and T-cell lymphocytes. Subsequent repletion of these lymphocytes leads to changes in adaptive immunity. Alemtuzumab is approved by the United States Food and Drug Administration (FDA) for the treatment of B-cell lymphocytic leukemia but has been investigated off-label in recent years for treatment of autoimmune diseases, including multiple sclerosis (MS). In MS treatment, alemtuzumab is administered as pulsed therapy, given once daily initially for 5 consecutive days and then for 3 consecutive days at 12-month intervals. Alemtuzumab has recently been compared to interferon beta 1-a in one phase II and two phase III trials in patients with relapsing-remitting MS. Results from the studies show alemtuzumab compared to interferon beta 1-a is associated with a greater reduction in the risk of sustained accumulation of disability and is more effective in reducing disease relapse rates. The treatment of MS continues to be a healthcare challenge due to the modest clinical benefit and adverse effect profiles of available disease modifying treatment options. Available data suggest alemtuzumab may offer better efficacy outcomes compared to traditional disease modifying therapies in patients with MS. However, the agent has not been compared to other new disease modifying medications that have been recently introduced.
Highlights
Multiple Sclerosis (MS) is a chronic, progressive inflammatory disease affecting the central nervous system (CNS), resulting in demyelination and irreversible axonal damage of nerves in the CNS
Alemtuzumab reduced the annualized relapse rate (ARR) 49.4% (P < 0.0001) over that observed in the interferon beta 1-a group, with relapses occurring in 35% of alemtuzumab and 53% of interferon beta 1-a patients, respectively
When the alemtuzumab 12 mg and 24 mg groups were compared for clinical outcomes, only new Magnetic resonance imaging (MRI) lesion formation was improved with the larger dosage [51]
Summary
Multiple Sclerosis (MS) is a chronic, progressive inflammatory disease affecting the central nervous system (CNS), resulting in demyelination and irreversible axonal damage of nerves in the CNS. There are several subtypes of MS classified based on clinical disease course, with the preponderance (approximately 85%) of patients experiencing a MS disease course characterized by symptomatic episodes lasting at least twenty-four hours followed by remission, or a symptom-free period, lasting at least thirty days. This clinical disease course is referred to as relapsing-remitting multiple sclerosis (RRMS). While current evidence is not sufficiently robust to confirm an increased risk of developing MS in patients with prior EBV infection, research of the association remains plausible [11,13,14,15]. It is interesting that the increased risk of developing MS in the offspring of two MS positive parents is comparable to that observed in monozygotic twins, independent of parental MS status [23,24]
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