Adding Tezepelumab to SCIT to Improve Cat Allergy Symptoms?

The asthma medication zepelumabadded to subcutaneous immunotherapy treatment (SCIT), may provide better and longer lasting symptom relief than allergy injections alone for patients with allergic rhinitis caused by cat allergens, based on Phase 1/2 results clinical test.

“One year of allergen immunotherapy [AIT] combined with tzepelumab was significantly more effective than SCIT alone in reducing the nasal response to allergen provocation at the end of treatment and one year after discontinuation of treatment,” said study lead author Jonathan Corren. , MD, from the University’s David Geffen School of Medicine. of California, Los Angeles, and his colleagues write in The Journal of Allergy and Clinical Immunology.

“This persistent improvement in clinical response was accompanied by reductions in nasal transcripts for several immunological pathways, including mast cell activation.”

The study was cited in a Press release from the National Institutes of Health (NIH) who said the approach could work similarly with other allergens.

The United States Food and Drug Administration (FDA) recently tézepelumab approved for the treatment of severe asthma in persons aged 12 years and over. Tezelumab, a monoclonal antibody, works by blocking thymic stromal lymphopoietin (TSLP).

“Cells that line the surface of organs like the skin and intestines or that line the inside of the nose and lungs rapidly secrete TSLP in response to signals of potential danger,” according to the NIH press release. “In allergic diseases, TSLP helps initiate an excessive immune response to otherwise harmless substances like cat dander, causing inflammation of the airways that results in the symptoms of allergic rhinitis.”

Test an improved strategy

The double-blind CATNIP trial was conducted by Corren and colleagues at nine sites in the United States. The trial included patients aged 18 to 65 who had had moderate to severe cat-induced allergic rhinitis for at least 2 years from 2015 to 2019.

The researchers excluded patients with recurrent acute or chronic sinusitis. They excluded patients who had experienced SCIT with a cat allergen in the past 10 years or sensitivity to seasonal or perennial allergens during nasal provocations. They also excluded people with a history of persistent asthma.

In the parallel design study, 121 participants were randomly assigned to four groups: 32 patients were treated with intravenous tezepelumab plus cat SCIT, 31 received the allergy shots alone, 30 received tezepelumab alone and 28 received placebo alone for 52 weeks, followed by 52 weeks of observation.

Participants received SCIT (10,000 bioequivalent allergy units [BAU] per milliliter) or matched placebo via weekly subcutaneous injections in increasing doses for approximately 12 weeks, followed by monthly maintenance injections (4000 BAU or maximum tolerated dose) until week 48.

They received tzepelumab (700 mg IV) or matching placebo 1–3 days before SCIT injections or SCIT placebo once every 4 weeks through week 24, then before or on the same day as SCIT injections or placebo until week 48.

Efficiency measures

Participants also received nasal allergy challenges – a spritz of a nasal spray containing cat allergen extract into each nostril at screening, baseline, and weeks 26, 52, 78, and 104. The researchers recorded the participants’ total nasal symptom score (TNSS) and peak nasal inspiratory flow at 5, 15, 30 and 60 minutes after the spray and every hour until 6 hours after the challenge. Blood and nasal cell samples were also taken.

The research team performed skin testing using serial dilutions of cat extract and an intradermal skin test (IDST) using the concentration of allergen that produced an early response of at least 15mm at baseline. . They measured the early phase responses for both tests at 15 minutes and the late phase response to the IDST at 6 hours.

They measured serum levels of cat dander-specific IgE, IgG4, and total IgE using a fluorinated enzyme immunoassay. They measured serum IL-5 and IL-13 using a high-sensitivity single-molecule digital immunoassay and performed nasal brushing using a 3 mm cytology brush 6 hours after a nasal allergy. They performed whole-genome transcriptional profiling on the extracted RNA.

Combination therapy worked better and longer

Combination therapy worked best during its administration. Although the allergy shots alone stopped working after they were stopped, the combination continued to benefit participants 1 year after this therapy ended.

  • At week 52, statistically significant reductions in TNSS induced by nasal allergic provocations occurred in patients receiving tezepelumab plus SCIT compared to patients receiving SCIT alone.

  • At week 104, 1 year after the end of treatment, the primary endpoint of TNSS was not significantly different in the tzepelumab plus SCIT group than in the SCIT alone group, but the peak TNSS 0-1 hour was significantly lower in the combined treatment group than in the SCIT alone group. in the SCIT group alone.

  • In gene expression analysis from nasal epithelial samples, participants who had been treated with the combination but not with either therapy by themselves showed persistent modulation of nasal immunological environment, including decreased mast cell function. This is largely explained by a decrease in the transcription of the gene TPSAB1 (tryptase). Tryptase protein in nasal fluid also decreased in the combined group compared to the SCIT alone group.

  • Adverse and serious events, including infections and infestations as well as respiratory, thoracic, mediastinal, gastrointestinal, immune system and nervous system disorders, did not differ significantly between treatment groups.

Four independent experts hail the results

Patricia Lynne Lugar, MD, associate professor of medicine in the Division of Respirology, Allergy, and Critical Care Medicine at Duke University School of Medicine, Durham, North Carolina, found the results, particularly the durability of the one-year post-treatment response, surprising .

Dr. Patricia Lynne Lugar

“AIT is a very effective treatment that often provides prolonged symptom improvement and is ‘curative’ in many cases,” she said. Medscape Medical News by email. “If further studies show that tezepelumab offers long-term results, more patients may opt for combination therapy.

“An important strength of the study is its assessment of combination therapy responses on cell production and gene expression,” Lugar added. “The mechanism by which AIT modulates the allergic response is widely understood. Tezepelumab may augment this modulation to alter the Th2 response upon allergen exposure.”

Will payers cover the prohibitively expensive biologic?

Scott Frank, MD, associate professor in the Department of Family Medicine and Community Health at Case Western Reserve University School of Medicine in Cleveland, Ohio, called the study well-designed and rigorous.

Doctor Scott Frank

“The practicality of the approach may be limited by the need for intravenous administration of tezepelumab in addition to the traditional allergy vaccine,” he noted via email, “and the cost of this therapeutic approach does not is not addressed”.

Christopher Brooks, MD, clinical assistant professor of allergy and immunology in the department of otolaryngology at Ohio State University Wexner Medical Center in Columbus, Ohio, also pointed to the drug’s cost.

Dr Christopher Brooks

“Tezepelumab is currently an expensive biologic drug, so it remains to be seen whether patients and payers will be willing to pay for this complementary drug when AIT itself is still very effective,” he said. by email.

“AIT is most effective when given for 5 years, so it also remains to be seen whether the results and conclusions of this study would still be valid if performed during the typical treatment period of 5 years,” he added.

Dr Stokes Peebles

Stokes Peebles, MD, professor of medicine in the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University Medical Center in Nashville, Tennessee, called the study “very well designed by a group of highly respected researchers using well-matched studies populations.

“Tezepelumab has been shown to work in asthma, and there’s no reason to think it wouldn’t work in allergic rhinitis,” he said in a phone interview.

“However, while the results of the combination therapy were statistically significant, their clinical significance was unclear. Patients don’t care about statistical significance. They want to know if a drug will be clinically significant,” he said. he adds.

Many people avoid cat allergy symptoms by avoiding cats and, in some cases, avoiding people who live with cats, he said. Medical therapy, usually involving nasal corticosteroids and antihistamines, helps most people avoid cat allergy symptoms.

“Patients with bad allergies who have not done well with SCIT may consider adding tzepelumab, but this comes at a significant cost. If medical treatment does not work, allergy shots are available at around 3 $000 a year. Adding tezepelumab costs about $40,000 more a year,” he explained. “Does the slight clinical benefit justify the greatly increased cost?” »

The authors and uninvolved experts recommend further related research.

The research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. AstraZeneca and Amgen donated the drug used in the study. Corren reports financial relationships with AstraZeneca, and a co-author reports relevant financial relationships with Amgen and other pharmaceutical companies. The remaining co-authors report no relevant financial relationships.

J Allergy Clin Immunol. Published online October 9, 2022. Summary

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