Exploring Immunosuppression’s Role in ILD Treatment, with Aman Pande, MD, MS

New research is providing clinicians with an overview of the role of immunosuppression therapy in non-idiopathic pulmonary fibrosis (IPF) interstitial lung disease (ILD).1

The data were presented at the American Thoracic Society (ATS) International Conference 2025 by Aman Pande, MD, MS, a pulmonary critical care physician at Cleveland Clinic, and suggest use of immunosuppressive treatment in this patient population may not meaningfully affect fibrosis progression.1

“It gets really tricky when you've got 200 different varieties of rare conditions,” Pande explained to HCPLive, citing the heterogeneity of ILD as a key barrier to effectively understanding and managing it.

IPF, which is considered to be a purely fibrotic disease and comprises a large majority of ILDs, was previously treated with immunosuppression, until the 2012 PANTHER trial revealed this approach is both ineffective and dangerous in this particular patient population.2 However, for patients with non-IPFs who have more underlying inflammatory components, the potential role of immunosuppression is not well understood.1

“If you set IPF aside and you look at all these other diseases where there is a component of underlying inflammation, we try to treat these with various immunosuppressants, and we think for individual patients that we are helping them,” Pande explained. “But as we know, this needs to be scientifically evaluated so that we can make sure that we're doing the right thing.”

To address this gap in research, he and colleagues examined data from Cleveland Clinic’s registry of patients seen in their ILD clinic. Patients were grouped based on whether they were prescribed steroids and/or other immunosuppressants at the first visit. Investigators used propensity scores (PS) for treatment to balance covariates prior to outcome analyses. Follow-up pulmonary function data was analyzed to see how many patients had a 10% relative decline in forced vital capacity (FVC) over a 24-month period.1

Among a cohort of 657 patients, 338 (51.4%) were prescribed immunosuppression. Investigators noted these patients were younger (median age 62.6 vs 67.7 years), but had a higher comorbidity index, more impaired pulmonary function (FVC 2.46L [1.84, 3.16] vs 2.63L [2.08, 3.30]) and were more often on supplemental oxygen (37.9% vs 20.4%). Investigators called attention to 231 patients with connective tissue disease (CTD) ILD in the cohort, most of whom (73.6%) received immunosuppression.1

A total of 196 (29.8%) patients in the undifferentiated cohort went on to develop progressive fibrosis over the next 2 years, and 305 (46.4%) upon further observation (median, 4.2 years). The unadjusted odds ratio (OR) for progressive fibrosis over the first 2 years was 1.07 (95% CI, 0.76-1.49) which did not change after direct adjustment for PS. Further 1:1 PS matching yielded an OR for progression of 1.01, ATT weighting an OR of 0.92, and a final double robust approach an OR of 0.91 (95% CI, 0.57-1.47).1

“What we found was, by all these other methods, as soon as you start adjusting for the fact that the groups are unbalanced, you find there is absolutely no progression of fibrosis,” Pande said. “We would have liked to show the opposite, that it actually is protective, but it didn't play out. But at least we can say that we're not harming our patients by doing these things. Hopefully, down the line, we'll be able to tease out which groups benefit more than others.”

Editors’ note: Pande has relevant disclosures with Boehringer Ingelheim.

References

1. Pande A, Chen PH, McCully J, et al. Treatment of Interstitial Lung Diseases With Immunosuppressant Medications. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.

2. The Idiopathic Pulmonary Fibrosis Clinical Research Network. Prednisone, Azathioprine, and N-Acetylcysteine for Pulmonary Fibrosis. N Engl J Med. doi:10.1056/NEJMoa1113354