Rhinitis, sinusitis, and ocular diseases
Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis

https://doi.org/10.1016/j.jaci.2005.09.036Get rights and content

Background

Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis.

Objectives

We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT.

Methods

Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 μg Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy.

Results

Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044).

Conclusion

Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.

Section snippets

Patients

Patients between ages 18 and 50 years with a minimum 2-year history of ragweed allergic rhinitis and no recent immunotherapy were enrolled at 3 US centers where ragweed seasons were historically similar in timing and severity. The protocol was reviewed and approved by the National Institute of Allergy and Infectious Diseases (NIAID) Allergy and Asthma Data and Safety Monitoring Board and the Institutional Review Boards at each institution. All patients signed an informed consent. Patients were

Patient demographics

A total of 159 patients were randomized equally into the 4 treatment arms between April 7 and May 13, 2003, and this group constituted the safety sample (Table I). Baseline characteristics were similar among the 4 treatment arms, with no significant differences in age, sex, race, weight, height, body mass index, IgE level, or percentage of patients who had previously received allergy immunotherapy. The mean IgE level (IU/mL) was 106 (range, 10-650).

Treatment disposition

One hundred fifty-nine patients received at

Discussion

This study has demonstrated the potential utility of omalizumab pretreatment in allergen-specific immunotherapy of ragweed-induced allergy rhinitis. It is unique in showing that omalizumab pretreatment can provide substantial protection against acute allergic reactions, including anaphylaxis, during a RIT protocol.

Pretreatment of patients with omalizumab for 9 weeks reduced the rate of anaphylactic events during RIT by almost 80%. All systemic reactions were decreased in the omalizumab plus

References (35)

Cited by (331)

  • Future Directions of Allergen Immunotherapy for Allergic Rhinitis: Experts’ Perspective

    2024, Journal of Allergy and Clinical Immunology: In Practice
  • Optimizing drug inhibition of IgE-mediated anaphylaxis in mice

    2022, Journal of Allergy and Clinical Immunology
View all citing articles on Scopus

Disclosure of potential conflict of interest: Y. Deniz works at and owns stock in Genentech. M. Mokhtarani is employed by Rinat Neuroscience. Z. Ballas has consultant arrangements with Roche, Corixa, and Baxter, and has received grants from the National Institutes of Health and Department of Veterans Administration Merit Review. J. Kline is on the speakers bureau for Merck, Genentech, and GlaxoSmithKline. W. Busse has consultant arrangements with Dynavax, Fujisawa, Genentech, Hoffman La Roche, Isis, Merck, Novartis, Schering, and Wyeth; has received grant support from Altana, Aventis, Dynavax, GlaxoSmithKline, Hoffman La Roche, Pfizer, and Wyeth; is on the speakers bureau for GlaxoSmithKline and Merck; and is on the advisory board for AstraZeneca, Aventis, Merck, Pfizer, and Schering. T. Casale has consultant arrangements, has received grants, and is on the speakers bureau for Novartis and Genentech. R. Townley has received grants from Novartis. The rest of the authors have no conflict of interest to disclose.

Conducted by the Immune Tolerance Network in collaboration with Genentech, Inc. The Immune Tolerance Network is supported by the National Institutes of Health and the Juvenile Diabetes Research Foundation.

View full text