In a recent study published in Journal of Allergy and Clinical Immunologya team of researchers from the United States (USA) investigated the effect of a monoclonal antibody against thymic stromal lymphopoietin (TSLP) on the effectiveness of subcutaneous allergen immunotherapy (SCIT) in patients with allergic rhinitis.
A large proportion of the US population is affected by allergic rhinitis, and allergy immunotherapy is widely used to treat severe allergic rhinitis in patients unresponsive to other pharmacological treatments.
However, the inconsistent response to immunotherapy and the long duration of treatment have prompted the search for more effective methods of immunotherapy, such as methods combined with cytokine inhibitors.
The epithelial-derived cytokine TSLP is known to stimulate the production of T helper type 2 cells and activate eosinophils, mast cells, and innate lymphoid type 2 cells, thereby increasing sensitivity and inflammation during allergies. Patients with severe asthma were given tezepelumab, a monoclonal antibody against TSLP, and experienced improvements in lung function and overall outcomes.
The role of tezepelumab in reducing serum levels of interleukin and immunoglobulin E (IgE) suggests its potential use as an adjuvant in allergic immunotherapy.
In this study, the team conducted a double-blind, placebo-controlled, randomized trial that included patients aged 18 to 65 years with at least a two-year clinical history of moderate to severe allergic rhinitis caused by cat allergen. . Positive results of the skin prick test with cat extract and cat allergen were required for inclusion in the study. Patients were excluded if they had previously received SCIT cat allergen or had a history of chronic or acute sinusitis, persistent asthma, or concurrent allergy during the study.
Randomized groups received one of four treatment regimens including cat allergen SCIT and tezepelumab, cat allergen SCIT alone, tezepelumab, or placebo for 52 weeks, followed by a 52-week observation period.
During the study, patients were challenged with cat extract nasal allergen during screening and at baseline, weeks 26, 52, 78, and 104. Total nasal symptom scores and peak nasal inspiratory flow were recorded after each nasal allergen challenge at 5, 15, and 30 minutes and hourly for up to six hours. Skin prick and intradermal skin tests were also performed at various time points to determine early and late phase responses.
Cat allergen-specific IgE and IgG4 levels and total serum IgE levels were measured. Immunoassays measured serum levels of interleukins (IL) 5 and 13. Endpoints were total nasal symptom scores, peak nasal inspiratory flow measurements, and responses to skin pricks and intradermal skin tests at various time points. Local symptoms were classified as adverse reactions if they interfered with sleep or activity.
In addition, ribonucleic acid (RNA) was extracted from nasal swab cells and used for genome-wide transcriptional profiling.
Results reported a significant reduction in nasal allergen-induced nasal symptom total scores at week 52 in patients treated with SCIT tezepelumab and cat allergen compared to patients treated with SCIT alone. Although the area under the curve for total nasal symptom scores was not significantly lower in the tezepelumab plus SCIT group compared to the SCIT alone group at 104 weeks, the maximum total nasal symptom score was significantly lower.
The results also indicated partial maintenance of tolerance, with patients treated with tezepelumab and SCIT having a reduction in peak nasal symptoms for one year after treatment discontinuation. In comparison, while ongoing SCIT monotherapy showed significant improvement compared with placebo, the results were not maintained after discontinuation of treatment.
Transcriptional profiling revealed sustained downregulation of genes associated with type 2 inflammation and altered nasal mast cell functions in patients treated with tezepelumab and SCIT. Positive clinical effects in the tezepelumab and SCIT group were significantly associated with tryptase gene downregulation (TPSAB1), which also led to a decrease in tryptase protein in the nasal fluid.
Patients receiving tezepelumab, either alone or in combination with SCIT, experienced reductions in total and specific IgE to cat allergen during and after treatment. Since TSLP levels returned to normal after discontinuation of treatment, the authors believe that the continued reduction in IgE levels indicates a prolonged impact of TSLP blockade on IgE-producing B cells.
Overall, the results suggest that the effect of tezepelumab in inhibiting the action of TSLP improves the efficacy and duration of SCIT treatment in patients with allergic rhinitis, with sustained tolerance observed for one year after discontinuation of treatment.
Link to journal:
- Corren, J., Larson, D., Altman, MC, Segnitz, RM, Avila, PC, Greenberger, PA, Baroody, F., Moss, MH, Nelson, H., Burbank, AJ, Hernandez, ML, Peden, D., Saini, S., Tilles, S., Hussain, I., Whitehouse, D., Qin, T., Villarreal, M., Sever, M., & Wheatley, LM (2022). Effects of combined treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: a randomized controlled trial. Journal of Allergy and Clinical Immunology. doi: https://doi.org/10.1016/j.jaci.2022.08.029 https://www.sciencedirect.com/science/article/abs/pii/S0091674922013331#!
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