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

Abstract

Anti-IgE therapy with omalizumab, a recombinant humanized monoclonal antibody, has anti-inflammatory effects in allergic asthma and rhinitis. Although omalizumab has been exceptionally safe, reactions after its administration have been reported. The goal of this study was to assess two patients who experienced apparent anaphylaxis after omalizumab administration. Two cases of apparent anaphylaxis after omalizumab administration are reported with diagnostic evaluation using skin testing and unique IgE and IgG anti-omalizumab serological assays. At the time of evaluation, both atopic asthmatic patients had total (free and bound) serum IgE levels of 199 kIU/L (100% free) and 200 kIU/L (80% free and 20% bound), respectively. Epicutaneous skin tests to omalizumab were negative at 150 mg/mL of omalizumab in both subjects and the nonexposed negative control subject. Intradermal skin tests were positive at 0.15 mg/mL in subject 1 and negative at 1.5 mg/mL of omalizumab in subject 2 and the control subject. Intradermal testing to polysorbate produced significant wheal/flare reaction in subject 2 but not in the negative control subject. Serological assays for IgE or IgG antibodies reactive with omalizumab were negative. The in vitro and in vivo immunologic data support the conclusion that the adverse reactions experienced by two patients after omalizumab administration after more than a year of successful omalizumab therapy for asthma were likely anaphylactoid in nature. Polysorbate, an excipient in omalizumab, is known to cause similar reactivity to other medicines and is the most likely cause of these reactions.

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

“…[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.…”

Effect of Ions on Agitation- and Temperature-Induced Aggregation Reactions of Antibodies

“…While this risk can be managed to a significant degree by the addition of such compounds, their degradation products have been found to react with proteins (42,43), presenting covalent modification risks. There are also reports of polysorbate 80 causing hypersensitivity reactions (44) and anaphylaxis (45) in patients administered therapeutic protein formulations. The proteins themselves can offer some protection from aggregation at the air/water interface: the rate of agitation-induced aggregate formation, in terms of percentage conversion per unit time, has been shown to decrease with increasing protein concentration (46).…”

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008*

“…The relative efficiency of this treatment compared to H 1 -antihistamines and intranasal glucocorticosteroids needs to be established. Omalizumab was shown in clinical trials and postmarketing surveillance studies to induce rare (0.1% of treated patients) but potentially severe anaphylactic or anaphylactoid reactions (1740,1741) leading to a change in the labeling. It is recommended that omalizumab should be administered to patients only in a healthcare setting with direct medical supervision for 2 h following the first three injections.…”