Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma

doi:10.1016/j.jaci.2007.09.022

Journal of Allergy and Clinical Immunology

Volume 120, Issue 6, December 2007, Pages 1378-1381

https://doi.org/10.1016/j.jaci.2007.09.022 Get rights and content

Background

Risk of anaphylaxis is included in the prescribing information for omalizumab, but the nature of these reactions merits further elaboration.

Objective

To describe cases of anaphylaxis associated with omalizumab administration in patients with asthma.

Methods

We reviewed spontaneous postmarketing adverse event reports submitted to the US Food and Drug Administration's Adverse Event Reporting System database and to the manufacturers of omalizumab and cases published in the literature through December 2006. Diagnostic criteria for anaphylaxis outlined by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network were used to screen cases.

Results

One-hundred twenty-four cases of anaphylaxis associated with omalizumab administration in patients with asthma were identified. Many cases had a delayed onset of symptoms beyond 2 hours after dose administration. Many cases were also characterized by a protracted progression, with individual signs and symptoms of anaphylaxis staggered over hours. Review of the case reports did not reveal any predictive risk factors for the delayed onset or protracted progression of anaphylaxis.

Conclusion

Omalizumab-induced anaphylaxis may be characterized by a delayed onset and a protracted progression of symptoms.

Clinical implications

The unusual timing of anaphylaxis in these cases challenges our understanding of anaphylaxis. A delayed onset of symptoms and protracted progression of anaphylaxis should be taken into account when administering omalizumab.

Section snippets

Methods

We reviewed spontaneous adverse event reports submitted to the US Food and Drug Administration's Adverse Event Reporting System database and to the manufacturers of omalizumab from June 2003 to December 2006, as well as published cases in the literature.3, 4, 5 These data were voluntarily submitted to Adverse Event Reporting System, and no additional information was available. The estimated exposure to omalizumab over this period was about 57,300 patients. By using diagnostic criteria for

Results

We identified 124 cases of anaphylaxis to omalizumab (Table I). Eighty-three percent (101 of 121 cases with sex reported) of the patients were female, and the mean age was 43 years (range, 9-78 years). Thirty-nine percent (n = 48) of the cases were first-dose reactions. Approximately ⅓ (n = 44) occurred after the third dose or higher; in some of these cases, patients had been receiving omalizumab therapy for a year or more before the anaphylactic reaction. As reported, 89% (n = 110) displayed

Discussion

Anaphylaxis is commonly considered to be an immediate systemic response to an agent, with signs and symptoms occurring simultaneously or in rapid sequence. In certain situations, a biphasic response may be observed, with a second wave of symptoms presenting generally within 8 hours of the initial event. These 124 cases of omalizumab-induced anaphylaxis challenge the typical model of anaphylaxis and are noteworthy for cases with delayed onset and protracted progression of symptoms.

Delay in onset

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Citation Excerpt :
More than half the cases of anaphylaxis to omalizumab occur less than 1 hour after medication administration. However, delayed reactions (>24 hours after the injection) and a protracted course, with symptoms progressively developing over the course of several hours, have been reported.506,507 Two patients with symptom onset more than 24 hours after the injection were rechallenged and both had recurrent reactions, strengthening the causality of omalizumab in these reactions.507

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: Disclosure of potential conflict of interest: The authors are employed by the US Food and Drug Administration.

: The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the US Food and Drug Administration.

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Food allergy, anaphylaxis, dermatology, and drug allergyDelayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Methods

Results

Discussion

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

J Pediatr

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Anaphylactoid reactions in two patients after omalizumab administration after successful long-term therapy

Allergy Asthma Proc

Food allergy, anaphylaxis, dermatology, and drug allergy
Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma