Anti-fibrotic therapy and lung transplant outcomes in patients with idiopathic pulmonary fibrosis

Author:

Astor Todd L.1,Goldberg Hilary J.2,Snyder Laurie D.3,Courtwright Andrew4,Hachem Ramsey5,Pena Tahuanty6,Zaffiri Lorenzo3,Criner Gerard J.7,Budev Marie M.8,Thaniyavarn Tany2,Leonard Thomas B.9,Bender Shaun9,Barakat Aliaa10,Breeze Janis L.11,LaCamera Peter12ORCID

Affiliation:

1. Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA

2. Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA

3. Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Durham, NC, USA

4. Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Philadelphia, PA, USA

5. Division of Pulmonary and Critical Care Medicine, Washington University, St. Louis, MO, USA

6. Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA

7. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA

8. Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA

9. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA

10. ILD Collaborative, Boston, MA, USA

11. Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA

12. Division of Pulmonary, Critical Care and Sleep Medicine, St. Elizabeth’s Medical Center, 736 Cambridge Street, Boston, MA 02135, USA

Abstract

Background: It is unclear whether continuing anti-fibrotic therapy until the time of lung transplant increases the risk of complications in patients with idiopathic pulmonary fibrosis. Objectives: To investigate whether the time between discontinuation of anti-fibrotic therapy and lung transplant in patients with idiopathic pulmonary fibrosis affects the risk of complications. Methods: We assessed intra-operative and post-transplant complications among patients with idiopathic pulmonary fibrosis who underwent lung transplant and had been treated with nintedanib or pirfenidone continuously for ⩾ 90 days at listing. Patients were grouped according to whether they had a shorter (⩽ 5 medication half-lives) or longer (> 5 medication half-lives) time between discontinuation of anti-fibrotic medication and transplant. Five half-lives corresponded to 2 days for nintedanib and 1 day for pirfenidone. Results: Among patients taking nintedanib ( n = 107) or pirfenidone ( n = 190), 211 (71.0%) had discontinued anti-fibrotic therapy ⩽ 5 medication half-lives before transplant. Anastomotic and sternal dehiscence occurred only in this group (anastomotic: 11 patients [5.2%], p = 0.031 vs patients with longer time between discontinuation of anti-fibrotic medication and transplant; sternal: 12 patients [5.7%], p = 0.024). No differences were observed in surgical wound dehiscence, length of hospital stay, or survival to discharge between groups with a shorter versus longer time between discontinuation of anti-fibrotic therapy and transplant. Conclusion: Anastomotic and sternal dehiscence only occurred in patients with idiopathic pulmonary fibrosis who discontinued anti-fibrotic therapy < 5 medication half-lives before transplant. The frequency of other intra-operative and post-transplant complications did not appear to differ depending on when anti-fibrotic therapy was discontinued. Registration: clinicaltrials.gov NCT04316780: https://clinicaltrials.gov/ct2/show/NCT04316780

Funder

This study was funded by Boehringer Ingelheim Pharmaceuticals, Inc (BIPI).

Publisher

SAGE Publications

Subject

Pharmacology (medical),Pulmonary and Respiratory Medicine

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