Objective Tracheobronchial stenosis (TBS) occurs in 13–27% of patients with granulomatosis with polyangiitis (GPA) and may cause life-threatening airway compromise. Despite advances in treatment, TBS remains difficult to manage, with frequent relapses and high procedural burden. The objective of this study was to evaluate the relationship between immunosuppressant use and frequency of relapse in patients with TBS-GPA.

Methods We performed retrospective review of patients with TBS-GPA seen at Johns Hopkins Medical Institutions between 2013-2024. Baseline demographic and clinical characteristics, immunosuppressant exposure, and tracheal dilation procedure dates were abstracted. A multivariate mixed effects Poisson regression model was used to assess the association between immunosuppressant exposures (rituximab, cyclophosphamide, methotrexate, azathioprine, leflunomide, and mycophenolate) and tracheal dilation incidence, adjusting for age, years since TBS diagnosis, anti-neutrophil cytoplasmic antibody (ANCA) status, GPA disease severity, and concomitant treatment with glucocorticoid injections.

Results A total of 56 patients with TBS-GPA were included in the analysis, with a mean follow-up duration of 9.9 years. In the adjusted mixed-effects Poisson model, patient-years on leflunomide were associated with a 64% lower incidence of tracheal dilations compared to periods off leflunomide (IRR 0.36, p = 0.002). No statistically significant associations were observed for the other immunosuppressants measured. Among other tested covariates, age under 40, severe GPA, and concomitant glucocorticoid injections were associated with higher dilation frequency.

Conclusion Leflunomide use was associated with a lower frequency of tracheal dilations in patients with TBS-GPA. These findings support the need for further evaluation of leflunomide as a treatment option in this population.

The authors have declared no competing interest.

This work is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers 2T32AR048522-21, P30 AR070254 and K24 AR080217. This work is also supported by the Jerome L. Greene Foundation and the Donald B. and Dorothy L. Stabler Endowed Fellowship.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/Institutional Review Board of Johns Hopkins Medical Institutions gave ethical approval for this work.

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Financial Support: This work is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers 2T32AR048522-21, P30 AR070254 and K24 AR080217. This work is also supported by the Jerome L. Greene Foundation and the Donald B. and Dorothy L. Stabler Endowed Fellowship.

We have no financial disclosures

All data produced in the present study are available upon reasonable request to the authors