Denvir Brendan, Shah Ami A, Hillel Alexander T, Seo Philip, Kim Ji Soo, Antiochos Brendan
Johns Hopkins Department of Medicine, Division of Rheumatology.
Johns Hopkins Department of Otolaryngology, Head and Neck Surgery.
medRxiv. 2025 Jul 25:2025.07.25.25332215. doi: 10.1101/2025.07.25.25332215.
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.
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.
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.
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.
气管支气管狭窄（TBS）发生于13%-27%的显微镜下多血管炎（GPA）患者中，可导致危及生命的气道阻塞。尽管治疗取得了进展，但TBS仍难以管理，复发频繁且手术负担重。本研究的目的是评估免疫抑制剂的使用与TBS-GPA患者复发频率之间的关系。
我们对2013年至2024年在约翰霍普金斯医疗机构就诊的TBS-GPA患者进行了回顾性研究。提取了基线人口统计学和临床特征、免疫抑制剂暴露情况以及气管扩张手术日期。使用多变量混合效应泊松回归模型评估免疫抑制剂暴露（利妥昔单抗、环磷酰胺、甲氨蝶呤、硫唑嘌呤、来氟米特和霉酚酸酯）与气管扩张发生率之间的关联，并对年龄、TBS诊断后的年数、抗中性粒细胞胞浆抗体（ANCA）状态、GPA疾病严重程度以及糖皮质激素注射的联合治疗进行了调整。
共有56例TBS-GPA患者纳入分析，平均随访时间为9.9年。在调整后的混合效应泊松模型中，与未使用来氟米特的时期相比，使用来氟米特的患者年数与气管扩张发生率降低64%相关（发病率比0.36，p=0.002）。对于其他检测的免疫抑制剂，未观察到统计学上的显著关联。在其他测试的协变量中，40岁以下、严重GPA以及糖皮质激素注射联合治疗与更高的扩张频率相关。
在TBS-GPA患者中，使用来氟米特与较低的气管扩张频率相关。这些发现支持进一步评估来氟米特作为该人群治疗选择的必要性。
