Prevalence of Adverse Drug Reactions: Comparing Crotalidae Immune Polyvalent Antivenoms F(ab')2 and F(ab) in a Galactose-alpha-1,3-galactose (alpha-gal) Endemic Area

Abstract

Study objectives: North American pit viper antivenoms, CroFab® and ANAVIP®, contain galactose-α-1,3-galactose (α-GAL) oligosaccharide. We compared adverse drug reactions, including presumed anaphylaxis, following administration of these antivenoms and investigated biological plausibility of these antivenoms leading to anaphylaxis in α-GAL-immunoglobulin (Ig) E-sensitized individuals.

Methods: We performed 2 studies. A retrospective chart review from the Arkansas Poison Center (May 2021 to July 2023) identified adverse drug reactions and presumed anaphylaxis in patients treated with crotaline antivenom. Two allergists (JK, LM), blinded to the antivenom used, adjudicated presumed anaphylaxis cases. To assess whether antivenoms could activate basophils from α-GAL-IgE-sensitized individuals, basophil activation tests were performed on blood from 5 α-GAL-IgE-sensitized participants with a history of mammalian meat allergy. Basophil activation was assessed by %CD63 upregulation.

Results: Adverse drug reactions without presumed anaphylaxis occurred in 7 out of 171 (4.1%) Fab recipients versus 8 out of 37 (21.6%) F(ab')₂ recipients (Δ=17.5%, 95% confidence interval [CI] [4.0 to 31.0]). Presumed anaphylaxis was observed in 3 out of 171 (1.8%) for Fab and 6/37 (16.2%) for F(ab')₂ (Δ=14.3%, 95% CI 2.5 to 26.2). In the basophil activation tests, the mean EC₅₀ for basophil CD63 activation was 144-fold higher for Fab (mean, [standard deviation]; 647 μg/mL of antivenom [627]) compared to F(ab')₂ (4.48 μg/mL of antivenom [2.75]).

Conclusion: We demonstrate a substantial incidence of adverse drug reactions and presumed anaphylaxis to crotaline antivenoms in an α-GAL endemic region, with F(ab')₂ antivenom associated with more reactions than F(ab). Clinicians in α-GAL endemic regions should be cautious in the use of antivenoms, especially for patients with α-GAL allergy.

Keywords: Alpha-gal; Anaphylaxis; Galactose-alpha-1,3-galactose; Snake antivenin; Snake antivenom.