In a recent study published in the Journal of Allergy and Clinical Immunology, a team of researchers from the United States (U.S.) investigated the impact of a monoclonal anti-thymic stromal lymphopoietin (TSLP) antibody on subcutaneous allergen immunotherapy (SCIT) efficacy among patients with allergic rhinitis.
A large portion of the U.S population is afflicted with allergic rhinitis, and allergic immunotherapy has been widely used to treat severe allergic rhinitis in patients who do not respond to other pharmacological treatments.
However, the non-uniform response to immunotherapy and the long treatment period has fueled the search for more effective immunotherapy methods, such as those 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 type 2 innate lymphoid cells, increasing sensitivity and inflammation during allergies. Patients with severe asthma have been administered tezepelumab, an anti-TSLP monoclonal antibody, and have reported improved lung function and overall outcomes.
The role of tezepelumab in reducing serum interleukin and immunoglobulin E (IgE) levels indicate its potential use as an adjuvant in allergic immunotherapy.
About the study
In the present study, the team conducted a double-blind, placebo-controlled, randomized trial that included patients between the ages of 18 and 65 with at least a two-year-long clinical history of moderate to severe allergic rhinitis induced by cat allergen. Positive results of a skin-prick test with cat extract and cat allergen nasal challenge were required for inclusion in the study. Patients were excluded if they had received prior cat allergen SCIT or had a history of chronic or acute sinusitis, persistent asthma, or concomitant allergy during the study.
The randomized groups received one of four therapeutic regimens comprising cat allergen SCIT and tezepelumab, only cat allergen SCIT, tezepelumab, or a placebo for a 52-week duration, which was followed by a 52-week observation period.
During the study, the patients underwent a nasal allergen challenge with cat extract during screening and at baseline, 26, 52, 78, and 104 weeks. The total nasal symptom score and peak nasal inspiratory flow were recorded after every nasal allergen challenge at five, 15, and 30 minutes and each hour for up to six hours. Skin-prick and intradermal skin tests were also conducted at different time points to determine early and late-phase responses.
Cat allergen-specific IgE and IgG4, and total IgE levels in the serum were measured. Immunoassays measured serum levels of interleukins (IL) 5 and 13. The endpoints were the total nasal symptom scores, peak nasal inspiratory flow measurements, and responses to skin-prick and intradermal skin tests at different time points. Local symptoms were classified as adverse reactions if they interfered with sleep or activity.
Additionally, ribonucleic acid (RNA) was extracted from cells procured by nasal brushing and used for whole genome transcriptional profiling.
The results reported a significant reduction in the total nasal symptom scores induced by nasal allergen challenge at 52 weeks in patients treated with tezepelumab and cat allergen SCIT compared to those treated only with SCIT. Although the area under the curve for total nasal symptom score was not significantly lower at 104 weeks for the tezepelumab and SCIT treatment group compared to the only SCIT treatment group, the peak total nasal symptom scores were considerably lower.
The results also indicated partial sustenance of tolerance, with patients treated with tezepelumab and SCIT experiencing reduced peak nasal symptoms for a year after discontinuation of treatment. In comparison, while ongoing SCIT monotherapy demonstrated significant improvement compared to the placebo, the results were not sustained after the treatment was stopped.
The transcriptional profiling revealed that patients treated with tezepelumab and SCIT experienced sustained downregulation of type 2 inflammation-related genes and altered nasal mast cell functions. The positive clinical effects in the tezepelumab and SCIT treatment group were significantly associated with the downregulation of the tryptase gene (TPSAB1), which also resulted in reduced tryptase protein presence in the nasal fluid.
Patients receiving tezepelumab, either alone or in combination with SCIT, experienced a reduction in total and cat allergen-specific IgE during and after treatment discontinuation. Since TSLP levels returned to normal after the treatment was discontinued, the authors believe that the continued reduction in IgE levels indicated a prolonged impact of TSLP blockage on the IgE-producing B cells.
Overall, the results indicated that the action of tezepelumab in inhibiting the action of TSLP improves the efficacy and duration of SCIT treatment in allergic rhinitis patients, with sustained tolerance exhibited for a year after discontinuation of treatment.
- Corren, J., Larson, D., Altman, M. C., Segnitz, R. M., Avila, P. C., Greenberger, P. A., Baroody, F., Moss, M. H., Nelson, H., Burbank, A. J., Hernandez, M. L., Peden, D., Saini, S., Tilles, S., Hussain, I., Whitehouse, D., Qin, T., Villarreal, M., Sever, M., & Wheatley, L. M. (2022). 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: https://doi.org/10.1016/j.jaci.2022.08.029 https://www.sciencedirect.com/science/article/abs/pii/S0091674922013331#!