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Interstitial lung disease
Original research
Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety
  1. Evans R Fernández Pérez1,
  2. James L Crooks2,
  3. David A Lynch3,
  4. Stephen M Humphries3,
  5. Tilman L Koelsch3,
  6. Jeffrey J Swigris1,
  7. Joshua J Solomon1,
  8. Michael P Mohning1,
  9. Steve D Groshong4,
  10. Kaitlin Fier5
  1. 1 Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, USA
  2. 2 Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA
  3. 3 Radiology, National Jewish Health, Denver, Colorado, USA
  4. 4 Pathology, National Jewsih Health, Denver, Colorado, USA
  5. 5 Clinical and Translational Research Unit, National Jewish Health, Denver, Colorado, USA
  1. Correspondence to Dr Evans R Fernández Pérez, National Jewish Health, Denver, Colorado, USA; fernandezevans{at}njhealth.org

Abstract

Background Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients.

Methods We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety.

Results After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference −0.76%, 95% CI −6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events.

Conclusions The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP.

Trial registration mumber NCT02958917.

  • hypersensitivity pneumonitis

Data availability statement

Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/thorax-2022-219795

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    Data availability statement

    Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • Contributors Study conception and design; wrote study protocol and statistical analysis plan: ERFP. Wrote statistical analysis plan and performed statistical analysis: JLC. Wrote imaging plan and performed imaging analysis: DAL, TLK, SH. Wrote histological analysis plan and performed histological analysis: SDG. Monitoring of data collection for the whole trial, study coordination and execution: ERFP, KF. All authors were involved in analysing and interpreting study results, contributed to the manuscript from the outset and read and approved the final draft. All authors are the guarantor of the paper and take responsibility for the work’s integrity as a whole from inception to published article.

    • Funding This study was funded by Genentech (ML29875).

    • Competing interests ERFP reports a relationship with Genentech, Boehringer Ingelheim and with National Heart Lung and Blood Institute that includes funding grants. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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