Monoclonal antibody improves immunotherapy against feline allergens

News release

Tuesday, October 11, 2022

The approach tested in the NIH study is expected to work similarly for other allergens.

An experimental approach to improving a standard cat allergy treatment made it more effective and faster-acting, and the benefits persisted a year after treatment ended, a study supported by the National Institutes of Health found. The findings were published in Journal of Allergy and Clinical Immunology.

Allergen immunotherapy, often called allergy shots, is a long-term treatment that reduces allergy symptoms in people with conditions such as allergic rhinitis or allergic asthma by reducing their sensitivity to allergens. However, achieving lasting relief of symptoms requires at least three years of allergy shots and does not work for everyone.

“People with chronic allergy symptoms may suffer from reduced productivity and quality of life,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the NIH. “The development of allergen immunotherapy regimens that work better and faster than those currently available would provide much-needed relief for many people.”

To that end, NIAID-supported researchers tested whether administering a monoclonal antibody called tezepelumab plus cat allergy vaccines to people with allergic rhinitis caused by cat allergens would safely provide better and faster long-lasting relief of symptoms , than allergy shots alone. Allergic rhinitis involves inflammation of the nasal membranes and causes symptoms such as sneezing, runny nose, stuffy nose, watery eyes, problems with smell, and itching in the nose, mouth, or eyes.

The phase 1/2 clinical trial, called CATNIP, was led by Dr. Jonathan Koren and conducted by the NIAID-funded Immune Tolerance Network. Dr. Koren is an associate clinical professor of medicine at the UCLA David Geffen School of Medicine in Los Angeles. Tezepelumab was donated to the trial by Amgen Inc. of Thousand Oaks, California and AstraZeneca of Gaithersburg, Maryland.

Tezepelumab blocks a protein called thymic stromal lymphopoietin (TSLP), a type of cell signaling molecule or cytokine called alarmin. Cells that line the surface of organs such as the skin and gut, or that line the inside of the nose and lungs, rapidly secrete TSLP in response to signals of potential danger. In allergic disease, TSLP helps initiate an overreactive immune response to otherwise harmless substances such as cat dander, provoking airway inflammation that leads to the symptoms of allergic rhinitis.

The CATNIP study enrolled 121 adults ages 18 to 65 at nine medical centers in eight cities across the United States. Participants were randomly assigned to receive either tezepelumab plus subcutaneous injections for cat allergy, tezepelumab plus placebo injections, placebo plus allergy shots, or double placebo. No one knew who was taking which regimen until the end of the study. The treatment period lasted 48 weeks and the research team continued to follow the participants for one year after the end of the treatment.

To test how well each regimen worked, the research team gave participants one spray in each nostril of a nasal spray containing a cat allergen extract six times during the two-year study period. The research team recorded the level of nasal symptoms and airflow through the participants’ noses at five, 15, 30 and 60 minutes after receiving the nasal spray and every hour for up to five hours thereafter. In addition, blood and nasal cell samples were taken from the participants.

The researchers found that participants’ worst nasal symptoms were 36% lower at the end of treatment in the group that received tezepelumab plus allergy shots compared to the group that received only allergy shots, and with 24% lower a year later. These results show for the first time that adding a cytokine inhibitor to allergy shots can reduce allergic rhinitis symptoms for a sustained period after just one year of treatment, according to the researchers.

Analysis of blood and nasal cell samples revealed that the combination treatment caused changes in gene network activity that reduced the activation of allergy-related immune cells on the inner lining of the nose, helping to suppress allergic nasal symptoms.

With the successful outcome of the CATNIP trial, plans are underway for an NIAID-supported Phase 2 trial of tezepelumab plus oral immunotherapy for food allergy. In addition, CATNIP researchers are further analyzing the study data to understand how tezepelumab plus immunotherapy works at the cellular level, to potentially design additional studies that look at more health outcomes, and to identify people who may have the most benefit from this treatment combination.

NIAID conducts and supports research—at NIH, in the United States, and around the world—to study the causes of infectious and immune-mediated diseases and to develop better means of preventing, diagnosing, and treating these diseases. News releases, fact sheets, and other materials related to NIAID are available on the NIAID website.

For the National Institutes of Health (NIH):NIH, the national agency for medical research, includes 27 institutes and centers and is part of the US Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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References

J Corren et al. Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: a randomized controlled trial. Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2022.08.029 (2022).

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