Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies

Background: Natalizumab is a new therapeutic option for relapsing-remitting multiple sclerosis. As with other antibody therapies, hypersensitivity reactions have been observed. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis(AFFIRM) trial, infusion-related hypersensitivity reactions developed in 4% of patients, usually within 2 hours after starting the infusion. Objective: To report a significant, delayed, serum sickness-like, type III systemic allergic reaction to natalizumab. Design: Case report describing clinical follow-up and the serial measurement of antinatalizumab antibodies. Patient: A23-year-old man with relapsing-remitting multiple sclerosis developed a fever, arthralgias, urticarial exanthema, and a swollen lower lip during several days after his second infusion of natalizumab. Results: The patient developed a delayed, serum sickness-like, type III systemic allergic reaction to natalizumab. Five weeks after initiation of this therapy, he tested positive for antinatalizumab antibodies and exhibited persistent antibody titers 8 and 12 weeks later. His symptoms completely resolved with a short course of oral glucocorticosteroids. Conclusion: Clinicians and patients should be alert not only to immediate but also to significantly delayed substantial allergic reactions to natalizumab.