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Impact of Immune Checkpoint Inhibitor Therapy on Asthma Exacerbations: A Nationwide Retrospective Cohort Analysis
Abstract   Peer reviewed

Impact of Immune Checkpoint Inhibitor Therapy on Asthma Exacerbations: A Nationwide Retrospective Cohort Analysis

Manan Shah, Shyam Saravanan and Edward Schulman
Journal of allergy and clinical immunology, v 157(2), pp AB44-AB44
Feb 2026
DOI: https://doi.org/10.1016/j.jaci.2025.12.133

Abstract

Rationale Asthma is an inflammatory disease orchestrated by a variety of immune cells. Immune checkpoint inhibitors (ICIs), including pembrolizumab and nivolumab, are widely used in oncology but their impact on comorbid asthma, particularly exacerbation risk, remains unclear. This study investigates asthma exacerbations rates in patients receiving ICIs compared to matched controls. Methods This retrospective cohort study utilized the TriNetX US Collaborative Network (>90 million patients). We found 2,329 patients (aged 18-80) with asthma undergoing ICI therapy for melanoma or renal cell carcinoma. Asthma subtypes were classified using ICD-10 codes (J45.2 - J45.909). Asthma exacerbation rates, defined as acute asthma exacerbation or status asthmaticus, were compared at 6, 12, and 24-months post-treatment initiation against propensity score-matched controls. Results Across all asthma subtypes, patients receiving pembrolizumab or nivolumab exhibited a modest reduction in exacerbation rates at 24 months (5.12% vs. 7.75%, p = 0.0004). Notably, patients with moderate to severe persistent asthma showed significant benefit at 24 months (6.82% vs. 13.26%, p = 0.0138). Conversely, dual therapy with nivolumab and ipilimumab did not demonstrate significant differences in exacerbation rates compared to controls. Conclusions ICI therapy, particularly pembrolizumab and nivolumab monotherapy, may confer protective effects against asthma exacerbations in select subgroups, especially those with moderate to severe persistent asthma. These findings suggest a potential immunomodulatory benefit of ICIs beyond oncologic indications. Further prospective studies are warranted to elucidate underlying mechanisms and validate clinical relevance.

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