Tezepelumab in Allergic Rhinitis and Asthma Study (TEZARS)

Tezepelumab is a novel monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), a molecule implicated in allergic disease. The purpose of this open-label, unblinded, exploratory mechanistic pilot study will be to evaluate the efficacy of tezepelumab (1 subcutaneous injection of 210mg given once every 4 weeks) in participants with moderate to severe allergic asthma and concomitant seasonal and perennial AR (SAR and/or PAR) over 12 months. The tezepelumab in allergic rhinitis and asthma study (TEZARS) is a single-centre study. The trial will enrol 14 non-pregnant/non-lactating female and/or male comorbid allergic rhinitis (AR) and allergic asthma participants ages 18 to 65 years old from the Kingston, Frontenac, Lennox and Addington regions. An additional 5 non-allergic participants will be enrolled to participate in the baseline Nasal Allergen Challenge (NAC) visit and then will exit the study. Comorbid AR and allergic asthma participants attend the baseline NAC, then receive one dose of tezepelumab every 1 month for 12 months. A 6-month post-treatment follow-up NAC will be conducted one month following the sixth dose. A 12-month post-treatment follow-up NAC will be conducted two weeks following the twelfth dose. At each NAC visit, symptom scores and quality of life questionnaires, in addition to nasal fluid and blood samples will be collected at various time points. The investigators hypothesize that tezepelumab will improve AR-related outcomes (TNSS; Peak Nasal Inspiratory Flow, PNIF; Rhinitis Control Assessment Test, RCAT) that are stimulated by NAC with seasonal and perennial allergens in our study population. Secondarily, the investigators hypothesize tezepelumab will decrease the release of allergic mediators (i.e., IL-1b, IL-3, IL-4, IL-5, IL-6, IL-8, IL-9 IL-10, IL-13, IL-18, MCP-1, TNFα, RANTES, eotaxin, tryptase, chymase) and alarmins (i.e., TSLP, IL-25, and IL-33) in the nose following NAC. A decrease in the gene expression of TSLP and mast cell mediators (tryptase and chymase) is also anticipated. Furthermore, the number of both nasal and peripheral eosinophils and total and specific immunoglobulin E (IgE) following NAC will decline after tezepelumab treatment. Five non-atopic controls will undergo baseline NAC to confirm the reliability of allergic mediator and alarmin methodologies. The investigators also hypothesize asthma-related outcomes (spirometry; Fractional Exhaled Nitric Oxide, FeNO; Asthma Control Questionnaire 5, ACQ5) will improve following treatment with tezepelumab. Finally, the NAC protocol in an asthmatic population will be assessed.