Long-Term Pirfenidone for Restrictive Allograft Syndrome: A Case Series

Abstract

<h3>Purpose</h3> Restrictive allograft syndrome (RAS) after lung transplantation (LTx) carries a bad prognosis, with generally a poor survival limited to 1-2 years after diagnosis. RAS is typically characterized by parenchymal fibrosis and distortion of lung architecture, a restrictive pulmonary function decline and persistent pleuroparenchymal abnormalities on computed tomography. There is no established treatment for RAS, although case series have reported on off-label treatment with antifibrotic drugs, such as pirfenidone (PFD), in RAS. However, reported treatment duration with PFD up to now was <2 years. We aim to report on RAS patients treated with PFD for at least 2 years in our center, in whom we evaluated evolution of pulmonary function during treatment with PFD. <h3>Methods</h3> Patients treated with off-label PFD for RAS were retrospectively assessed; and patients treated with PFD for at least 2 years were included for analysis. FVC, FEV1, TLC and TLCO at start of PFD and during the last visit on PFD were evaluated. GraphPad Prism 9.0 was used to compare parameters at different time points (start vs. last). <h3>Results</h3> In our cohort of 28 RAS patients treated with PFD since 2013 (median duration 177.5 (64.5-359.8) days), we identified 4 RAS patients who were treated with PFD for a mean (±SD) duration of 5.2 (±1.1) years (range 3.8-6.3 years). In these patients, total follow-up was 10.4±3.1 years (3/4 patients currently alive), RAS was diagnosed 4.6 (±1.7) years post-LTx (2/4 patients had prior BOS) and PFD was started 6.0 (±2.5) years post-LTx. FVC at start of PFD was 2.40 (±1.24) L vs. 1.85 (±0.91) L (p=0.091) at last measurement, with a monthly decline of 9.5 (±7.7) mL/month during PFD treatment. FEV1 at start was 1.69(±0.86) L vs. 1.28 (±0.55) L (p=0.147) at last measurement, with a monthly decline of 8.0 (±10.0) mL/month during PFD treatment. TLC at start was 4.00 (±1.58) L vs. 2.82 (±0.60) L (p=0.080) at last measurement, with a monthly decline of 11.3 (±8.6) mL/month during PFD treatment. Also, TLCO did not significantly differ over time (p=0.258). <h3>Conclusion</h3> A subset of RAS patients may demonstrate significantly better long-term survival, in these patients progressive fibrosing interstitial lung disease may possibly be attenuated by antifibrotic drugs, such as PFD, which requires further investigation.