Acute Acalculous Cholecystitis Linked to Lemtrada Use in RRMS Patients, FDA Reports

Acute acalculous cholecystitis (AAC) is a rare but potentially life-threatening adverse effect linked to treatment with Lemtrada (alemtuzumab) in patients with relapsing-remitting multiple sclerosis (RRMS), according to a U.S. Food and Drug Administration review.

The study, “Acute acalculous cholecystitis — A new safety risk for patients with MS treated with alemtuzumab,” was published in the journal Neurology.

AAC is a disease affecting the gallbladder characterized by inflammation, which may lead to tissue death.

Initial product labeling for Sanofi Genzyme’s Lemtrada didn’t include AAC because of the low number of cases observed during clinical trials testing the therapy.

Based on a small case series of AAC associated with Lemtrada use in RRMS patients, the FDA’s Division of Pharmacovigilance conducted a review to evaluate AAC as a potential safety risk for patients taking the therapy.

Researchers searched the FDA Adverse Event Reporting System (FAERS) and medical literature for AAC cases associated with Lemtrada administration for MS and other clinical indications. The analysis identified eight reported cases meeting the case definition of AAC in association with Lemtrada use, found only in the FAERS database.

All eight cases were patients with RRMS. Seven of these patients developed AAC during or shortly after Lemtrada treatment, while one patient experienced AAC about six to seven weeks after completing the first Lemtrada course.

The team determined that four of the AAC cases were probably caused by Lemtrada use since no other predisposing factors toward AAC were found. The other four cases were classified as having a possible causal association with Lemtrada, but the link was not as robust due to the presence of AAC predisposing factors.

“The cases identified in this review differ from the typical AAC cases described in the medical literature based on female preponderance, lack of concurrent critical illnesses, inconsistent presence of other risk factors, and resolution with conservative treatment in the majority of cases,” the researchers wrote.

Females accounted for 80% of the cases, and there were no cases linked to critical illness, a common risk factor for AAC. Other risk factors for AAC, such as hypertension and diabetes mellitus, have been reported, but only one patient had preexisting hypertension in the group analyzed in this study.

These findings led to a Lemtrada label change to include AAC in the warnings and precautions.

“AAC represents a new relatively rare but potentially life-threatening adverse event associated with alemtuzumab use in patients with RRMS. Early conservative treatment seems to result in good outcome, although the natural history of AAC in the RRMS population is not well-defined,” the researchers said.

The team also emphasized that “awareness of this safety risk by general and specialty neurologists is important for prompt recognition and optimal management.”