Omalizumab May Improve Tolerance to Venom Immunotherapy

A new study suggests that adding omalizumab may help patients who experience allergic reactions during venom immunotherapy.1

“A semi-rush protocol with omalizumab loading 1 to 2 weeks prior was well tolerated,” wrote study investigator Kris Capper, MD, from Fiona Stanley Hospital in Western Australia, and colleagues.1

Venom immunotherapy remains the only disease-modifying treatment for honeybee venom allergy. However, some patients develop severe allergic reactions during therapy, leaving them vulnerable to both the venom allergy and its treatment. Investigators hypothesized that omalizumab, an anti-IgE monoclonal antibody, could improve venom immunotherapy tolerance.

To test this, they conducted a retrospective chart review to assess the efficacy of adjunct omalizumab in honeybee venom immunotherapy and to identify predictors of requiring omalizumab.1 The sample included 354 adults undergoing honeybee venom immunotherapy at Fiona Stanley Hospital from 2015 to 2024.

Among the sample, 57 (16%) experienced severe adverse events, and 36 (10%) received omalizumab. Predictors for omalizumab use included severe sting anaphylaxis, asthma, and elevated basal tryptase. Although most patients received omalizumab to manage venom immunotherapy-related adverse events, 1 patient used it to increase venom therapy dosing after reaching maintenance.

Among the 35 patients who took omalizumab while increasing their venom immunotherapy dose, 22 (63%) were able to continue treatment without needing omalizumab, 7 (20%) had to stop because of severe allergic reactions, and 5 (14%) remained on omalizumab. Excluding the 5 patients who chose not to or couldn’t continue omalizumab, the success rate had increased up to 73%.

The most common protocol used a 12-week venom immunotherapy dose increase up to 100 μg, with patients starting omalizumab (300 mg) 2 weeks before and then receiving 150 mg every 2 weeks until they reached maintenance. Most severe allergic reactions happened after stopping omalizumab. In 3 cases, these reactions were managed by restarting omalizumab and aiming for a higher maintenance venom immunotherapy dose.

Adverse events are not uncommon in venom immunotherapy. A 2015 meta-analysis of 4844 patients across 46 studies reported that 28.7% experienced adverse reactions, including systemic reactions in 14%.2

Managing such cases can be challenging. In 2021, a clinician sought guidance through the American Academy of Allergy, Asthma & Immunology’s “Ask the Expert” after a 68-year-old patient developed throat tightness and voice changes during venom immunotherapy.3 Responding expert Dennis K. Ledford, MD, FAAAI, a professor of allergy and immunology at the University of South Florida, advised increasing pre-treatment with high-dose H1 antihistamines and staggering different venoms (e.g., wasp on one day, mixed vespid on another). Ledford recommended considering omalizumab only if reactions persisted, given its cost, coverage limitations, and potential difficulty discontinuing the drug mid-therapy.

“The omalizumab is of potential value, but I have no recommendation on securing approval other than submitting the reference below and the practice parameter describing the benefit of omalizumab and venom immunotherapy for the treatment of a potentially life-threatening condition,” Ledford wrote.3

However, these new findings reinforce that omalizumab may serve as a valuable adjunctive therapy in patients who otherwise cannot tolerate venom immunotherapy, offering a path forward for continuing life-saving desensitization.1

References

1. Capper K, McGettigan B, Willis C, Stevenson B. Omalizumab enables bee venom desensitisation in patients with anaphylactic reactions to venom immunotherapy. J Allergy Clin Immunol Pract. Published online October 8, 2025. doi:10.1016/j.jaip.2025.09.038

2. Smith A. Dangers of Bee Venom Therapy. Hcplive.com. Published July 2015. Accessed October 16, 2025. https://www.hcplive.com/view/dangers-of-bee-venom-therapy

3. Anaphylaxis to venom immunotherapy. Aaaai.org. Published 2021. Accessed October 16, 2025. https://www.aaaai.org/allergist-resources/ask-the-expert/answers/2021/venom-immuno