Severe gastrointestinal adverse reactions including perforation, ulceration, hemorrhage, and obstruction: A fumaric acid ester class new safety risk.

Abstract

Background: Although gastrointestinal (GI) adverse reactions (ARs) were commonly observed in registrational clinical trials of fumarate acid ester (FAE) drugs for the treatment of multiple sclerosis, serious GI reactions were uncommon.

Objective: The objective of the study is to describe the serious GI ARs that supported the post-market safety labeling change for FAE drugs.

Methods: Review of the FDA Adverse Events Reporting System (FAERS) database and published medical literature was conducted to identify cases of serious GI events in patients taking FAE drugs.

Results: Forty-nine cases of GI ARs with clinical events of perforation, ulceration, hemorrhage, or obstruction causally associated with FAE drug use were identified. Most cases occurred within 4 months of FAE drug initiation and required hospitalization. Ten of the cases required red blood cell transfusions, nine cases required surgical intervention, and two cases resulted in a fatal outcome.

Conclusion: Review of postmarketing reports supported the identification of a class association between FAE drugs and serious GI ARs. As these reactions have implications for prescribing decisions and patient management, a safety labeling change was issued to add serious GI reactions to the Warnings and Precautions section of the prescribing information for FAE drugs.