Steroid-Sparing Agents Show Promise in Stabilizing Lung Function in Hypersensitivity Pneumonitis

Patients with hypersensitivity pneumonitis who were treated with mycophenolate mofetil or azathioprine for 12 months showed stable forced vital capacity (FVC) with no significant change from baseline, in a systematic review and meta-analysis.

Hypersensitivity pneumonitis, an immune-mediated lung disease, is triggered by inhaling organic or inorganic antigens, leading to inflammation of the small airways. The disease has varied presentations, and correctly identifying and removing the inciting agent can stop the progression of lung injury. However, many patients follow a progressive clinical course and develop purely fibrotic or mixed inflammatory and fibrotic disease.

Steroids have been the main treatment, but their many side effects have prompted investigations into alternative therapies, such as mycophenolate mofetil and azathioprine, to spare patients from prolonged steroid exposure.

Lung Function Stabilized Without Steroid Risks

In the current study, the researchers searched Medline and Embase for observational and experimental studies that reported FVC changes after 12 months of treatment with mycophenolate mofetil or azathioprine, either as monotherapy or in combination with steroids. They excluded case reports and case series with fewer than five patients, and in the final analysis, they separately considered studies reporting the outcome of interest in different cohorts.

After screening 534 studies, seven met their inclusion criteria. The final analysis comprised 434 patients across 12 cohorts, with results pooled using a single-arm meta-analysis. A random effects model was used to account for the high heterogeneity across observational studies.

Treatment with steroids was reported in 11 of the 12 cohorts, with 72% to 100% of patients receiving steroids.

When including the mycophenolate mofetil and azathioprine cohorts, the mean change in FVC after 12 months of therapy was +1.04%. For cohorts treated exclusively with mycophenolate mofetil (n=7), the mean FVC change over the same period was +0.16%. Due to the high heterogeneity for this outcome (I²=62.2%, R²=8.2980, P=0.0145), the researchers performed a subgroup analysis that excluded one study.

After this exclusion, the mean FVC change in mycophenolate mofetil cohorts at 12 months increased to +1.12%, and heterogeneity decreased significantly (I²=43.9%, R²=4.2522, P=0.1127). For azathioprine-treated patients, the mean FVC change at 12 months was +0.16%. The study team did not perform a subgroup analysis for azathioprine due to the limited number of available studies.

Both medications appeared to successfully stabilize lung function while avoiding the many side effects of glucocorticoids. The researchers recommend further investigation of the clinical and functional outcomes of patients with hypersensitivity pneumonitis who are treated with these steroid-sparing agents.

Reference

Barba AD, Maryam B, Asif M, et al. Effect of Azathioprine and Mycophenolate Mofetil on Lung Function Decline in Patients With Hypersensitivity Pneumonitis: A Systematic Review and Meta-Analysis. Presented at: CHEST 2025, October 19-22, 2025; Chicago.