- Design
- Multicentre retrospective target trial emulation (clone-censor-weight)
- Population
- 2,270 patients with non-IPF IIP, fibrotic HP or CTD-ILD
- Primary outcome
- 3-year transplant-free survival
- Effect
- No benefit in any subtype; non-IPF IIP HR 1.38 (95% CI 1.04–1.84); fHP HR 1.62 (1.09–2.40)
Using records of 2,270 patients with non-IPF fibrotic ILD from several centres, investigators emulated a randomised trial comparing starting mycophenolate or azathioprine within six months against not starting, with statistical weighting to balance the groups. The subtypes were non-IPF idiopathic interstitial pneumonia, fibrotic hypersensitivity pneumonitis and connective tissue disease-associated ILD.
Immunosuppression was not associated with better three-year transplant-free survival or slower lung function decline in any subtype. It was associated with worse survival in non-IPF idiopathic interstitial pneumonia (HR 1.38) and fibrotic hypersensitivity pneumonitis (HR 1.62).
Target trial emulation reduces but cannot remove confounding: clinicians may have started treatment in patients who looked more active or were declining. Randomised data support mycophenolate in systemic sclerosis-associated ILD, and current guidelines have not changed. But the result is a strong reason to reconsider starting immunosuppression by default in fibrotic disease without an inflammatory component, especially fibrotic hypersensitivity pneumonitis and unclassifiable fibrosis, and to discuss antifibrotic therapy for progressive disease instead.
- Reconsider routine mycophenolate or azathioprine in established fibrotic ILD without clear inflammatory features.
- Prioritise antigen avoidance in fibrotic hypersensitivity pneumonitis.
- Consider antifibrotic therapy for progressive pulmonary fibrosis regardless of subtype.
- Continue immunosuppression in connective tissue disease-associated ILD where guidelines and trials support it.
- Review patients already on immunosuppression for evidence of benefit at each visit.
Why it matters
It challenges one of the most common prescribing habits in ILD clinics.
Don't overread it
An emulated trial from observational data; it does not override randomised evidence or current guidelines.
The statistics, in plain English
A hazard ratio of 1.62 means a 62% higher rate of death or transplant in fibrotic hypersensitivity pneumonitis among those started on immunosuppression. Because treatment was not randomised, sicker patients may have been more likely to receive it, which could produce this pattern.
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