Fatal AEs Associated With Alemtuzumab for MS May Occur More Frequently Than Previously Thought

August 23, 2019

Fatal adverse events (AEs) associated with alemtuzumab for multiple sclerosis (MS) may occur more frequently than previously understood based on past published literature, researchers found.

Patients with multiple sclerosis (MS) should be careful when taking alemtuzumab (Lemtrada) as recent research has shown that the drug is associated with more fatal adverse events (AEs) than previously understood in the literature.

Research published in BMS Research Notes analyzed fatal AEs associated with alemtuzumab for MS. They searched EudraVigilance, the European Medicines Agency (EMA)’s database of suspected adverse reactions.

“Following regulatory approval of alemtuzumab for relapsing remitting MS in 2013 by the [EMA] and in 2014 by the [FDA], there have been reports of severe and even fatal suspected adverse effects,” the authors explained. Among those serious AEs are alveolar hemorrhage, neutropenia with staphylococcus infection, and autoimmune hemolytic anemia with necrotizing leukoencephalopathy.

They identified 10 total cases—9 with a probable causal relationship between the treatment and a fatal AE and 1 with a possible causal relationship. Of these cases, 9 were female and 1 was male.

Among the 10 cases, the shortest time to symptoms was 3 days and the patient had septic shock and multiple organ failure. The shortest time to death was 5 days and this was from the AE of intracerebral hemorrhage. The longest time to symptoms was 17 months and time to death was 18 months, both of which were the 1 possible case in which the patient developed agranulocytosis after a second course of alemtuzumab followed by Clostridium colitis infection, aspergillus pneumonia, and finally death from multiple organ failure.

The researchers also identified 5 cases of fatal AEs considered unlikely to be related to the treatment, as well as 2 cases in which infants weighing less than 500 g died within 1 day after induced labor to mothers who had been treated with alemtuzumab during pregnancy.

Overall only 4 of these cases had been previously published or reported on at meetings, while the remaining 6 cases had not been. The cases of fatal AEs were divided into 2 categories: (1) those that occurred early and were related to immunosuppression, hyperinflammation, or stroke; or (2) those that occurred months later and were associated with secondary autoimmunity, which is known to occur frequently in patients with MS treated with alemtuzumab.

In December 2018, FDA issued a warning that there were rare but serious cases of patients with MS treated with alemtuzumab experiencing stroke and tears in the lining of arteries in the head and neck. The result could be permanent disability and death.

“Patients, physicians and regulatory authorities should be aware of the serious risks associated with alemtuzumab treatment, which must be weighed against the high and durable clinical efficacy,” the authors concluded.

Reference

Holmøy T, Fevang B, Benee Olsen D, Spigset O, Bø L. BMC Res Notes. Adverse events with fatal outcome associated with alemtuzumab treatment in multiple sclerosis. 2019;12(1):497. doi: 10.1186/s13104-019-4507-6.