- Design
- Multicentre retrospective target trial emulation
- Population
- 2270 patients with non-IPF fibrotic ILD
- Primary outcome
- 3-year transplant-free survival
- Effect
- No benefit; fHP HR 1.62 (1.09–2.40), non-IPF IIP HR 1.38 (1.04–1.84)
A multicentre retrospective study used target trial emulation (clone-censor-weighting) in 2270 patients with non-IPF idiopathic interstitial pneumonia, fibrotic hypersensitivity pneumonitis or connective tissue disease-associated ILD, comparing starting mycophenolate or azathioprine within six months against not starting.
Immunosuppression was not associated with better three-year transplant-free survival in any subtype. It was associated with worse survival in non-IPF idiopathic interstitial pneumonia (HR 1.38, 95% CI 1.04–1.84) and fibrotic hypersensitivity pneumonitis (HR 1.62, 1.09–2.40). Lung function trajectories did not differ.
Immunosuppression is widely used in these conditions on limited trial evidence. This analysis does not prove harm — patients who are started on treatment may be sicker in ways records miss — but it adds weight to the case for randomised trials and for careful selection.
- Reserve immunosuppression in fibrotic ILD for patients with clear inflammatory features or progression, after multidisciplinary discussion.
- In fibrotic hypersensitivity pneumonitis, identify and remove the antigen before escalating treatment.
- Review whether existing immunosuppression is producing benefit at each follow-up.
- Results did not show harm in CTD-associated ILD, where evidence for immunosuppression is stronger.
Why it matters
It challenges a widely used treatment that rests on little randomised evidence.
Don't overread it
This is observational; it cannot show that immunosuppression causes harm, and practice should not change on it alone.
The statistics, in plain English
Target trial emulation tries to mimic randomisation with statistical weighting, but cannot balance factors that were not recorded. A hazard ratio of 1.62 means a 62% higher rate of death or transplant in the treated group.
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