New reports of serious side effects affecting the heart, blood vessels, lungs, and liver of patients with relapsing-remitting multiple sclerosis (MS) who are taking alemtuzumab (Lemtrada, Genzyme) have prompted the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) to launch a review and to place temporary restrictions on use of the drug while the review is ongoing.
In addition to the restrictions, PRAC has recommended an update of the product information for alemtuzumab to inform patients and healthcare providers about cases of immune-mediated conditions, including autoimmune hepatitis and hemophagocytic lymphohistiocytosis; problems with the heart and blood vessels that occur within 1 to 3 days of treatment, including bleeding in the lungs, heart attack, stroke, and cervicocephalic arterial dissection; and severe neutropenia.
Last year, the US Food and Drug Administration warned about the potential for "rare but serious" cases of ischemic and hemorrhagic stroke and cervicocephalic arterial dissection associated with alemtuzumab therapy, as reported by Medscape Medical News.
For now, the EMA advises that treatment with alemtuzumab only be initiated in adults with relapsing-remitting MS that is highly active despite treatment with at least two other disease-modifying therapies or in those who can't take other disease-modifying therapies.
For patients currently receiving alemtuzumab, vital signs should be monitored before and during intravenous infusion. If clinically significant changes are observed, discontinuation of infusion and additional monitoring, including ECG, should be considered, the EMA said.
Liver function tests before and during treatment are also advised. If a patient develops signs of liver damage, unexplained elevations in liver enzyme levels, or symptoms suggestive of hepatic dysfunction, the drug should only be readministered after careful consideration.
"Patients who develop signs of pathological immune activation should be evaluated immediately, and a diagnosis of hemophagocytic lymphohistiocytosis considered. Symptoms of immune activation may occur up to 4 years after the start of treatment," the EMA said.
Patients being treated with alemtuzumab who are benefiting from it may continue treatment in consultation with their physician, the PRAC said.
The committee will provide further information once their review of alemtuzumab is finished.
Cite this: PRAC Restricts Use of Alemtuzumab for MS Pending Ongoing Review - Medscape - Apr 12, 2019.