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.


METHODS
Case report describing clinical follow-up and the serial measurement of antinatalizumab antibodies.


METHODS
A 23-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.


CONCLUSIONS
Clinicians and patients should be alert not only to immediate but also to significantly delayed substantial allergic reactions to natalizumab.
Krumbholz
Markus
M
Institute for Clinical Neuroimmunology, Ludwig Maximilian University, Marchioninistrasse 15, 81377 Munich, Germany. krumbholz@neuro.mpg.de
Pellkofer
Hannah
H
Gold
Ralf
R
Hoffmann
Lisa Ann
LA
Hohlfeld
Reinhard
R
Kümpfel
Tania
T
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019138:Antibodies, Blocking / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D004487:Edema / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D004890:Erythema / Q000209:etiology; D020234:Gait Ataxia / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000188:drug therapy; D000069442:Natalizumab; D012713:Serum Sickness / Q000276:immunology / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D000069442:Natalizumab