NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

SESSION TITLE: Lung Transplantation: New Issues in 2022SESSION TYPE: Rapid Fire Original InvPRESENTED ON: 10/19/2022 11:15 am - 12:15 pmPURPOSE: Lung transplant candidates with idiopathic pulmonary fibrosis (IPF) are often treated with the antifibrotic medications nintedanib or pirfenidone. In pre-clinical studies, nintedanib was associated with tissue friability and bleeding, raising concern for peri-operative complications at the time of lung transplantation. Our transplant center currently discontinues nintedanib 1 week prior to transplant listing to avoid such potential complications. However, there are also data to suggest that cessation of antifibrotic therapy may be associated with precipitous clinical decline. Limited research has evaluated the risk of waitlist death following nintedanib discontinuation. We hypothesized that nintedanib cessation prior to transplant listing would be associated with increased waitlist mortality compared to treatment with pirfenidone.METHODS: We performed a retrospective study of 53 patients with interstitial lung disease (ILD) on antifibrotic therapy who were listed for lung transplantation at our institution from 1/2016-2/2021. Nintedanib (n=23) was discontinued 1 week prior to transplant listing, whereas pirfenidone (n=30) was continued through transplantation. The primary outcome was risk of death without transplantation and was assessed using Kaplan-Meier analysis. Other continuous variables were compared using Mann-Whitney U test and categorical variables were compared using Chi squared analysis.RESULTS: There were no significant differences in age, lung allocation score, ILD subtype, double lung transplant, pre-operative pulmonary function testing (FEV1, FVC, or DLCO), liters of supplemental oxygen at rest or with exertion, need for ECMO support, or 6-minute walk distance between patients treated with nintedanib or pirfenidone. Five patients on antifibrotic therapy (9.4%) died prior to transplantation [1 nintedanib (4.3%) and 4 pirfenidone (13.3%)]. Nintedanib cessation prior to listing was not associated with increased risk of waitlist death compared to continuation of pirfenidone therapy (Figure, p=0.495). There was no significant difference in waitlist duration between patients on nintedanib (median: 13 days, IQR: 5-26) compared to pirfenidone (21 days, IQR 8-61, p=0.199). Of patients on antifibrotic therapy that underwent transplant (n=48), nintedanib cessation was not associated with increased intra-operative transfusion volume (p=0.852), need for return to operating room for hemorrhage (p=0.164), ICU length of stay (LOS) (p=0.440), or hospital LOS (p=0.646).CONCLUSIONS: Our data show that nintedanib cessation is not associated with increased waitlist mortality in lung transplant candidates with ILD. There were no significant differences in pre- or peri-operative outcomes between waitlisted patients managed with nintedanib cessation compared to continuation of pirfenidone.CLINICAL IMPLICATIONS: Nintedanib cessation in lung transplant candidates is not associated with waitlist mortality.DISCLOSURES: No relevant relationships by Matthew BacchettaNo relevant relationships by Caitlin DemarestNo relevant relationships by Ashley DrenglerNo relevant relationships by David ErasmusNo relevant relationships by Alexis GoreeNo relevant relationships by Eric LambrightNo relevant relationships by Katie McPhersonno disclosure on file for Stephanie Norfolk;No relevant relationships by Ivan RobbinsNo relevant relationships by Ciara Shaverno disclosure submitted for Anil Trindade; SESSION TITLE: Lung Transplantation: New Issues in 2022 SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Lung transplant candidates with idiopathic pulmonary fibrosis (IPF) are often treated with the antifibrotic medications nintedanib or pirfenidone. In pre-clinical studies, nintedanib was associated with tissue friability and bleeding, raising concern for peri-operative complications at the time of lung transplantation. Our transplant center currently discontinues nintedanib 1 week prior to transplant listing to avoid such potential complications. However, there are also data to suggest that cessation of antifibrotic therapy may be associated with precipitous clinical decline. Limited research has evaluated the risk of waitlist death following nintedanib discontinuation. We hypothesized that nintedanib cessation prior to transplant listing would be associated with increased waitlist mortality compared to treatment with pirfenidone. METHODS: We performed a retrospective study of 53 patients with interstitial lung disease (ILD) on antifibrotic therapy who were listed for lung transplantation at our institution from 1/2016-2/2021. Nintedanib (n=23) was discontinued 1 week prior to transplant listing, whereas pirfenidone (n=30) was continued through transplantation. The primary outcome was risk of death without transplantation and was assessed using Kaplan-Meier analysis. Other continuous variables were compared using Mann-Whitney U test and categorical variables were compared using Chi squared analysis. RESULTS: There were no significant differences in age, lung allocation score, ILD subtype, double lung transplant, pre-operative pulmonary function testing (FEV1, FVC, or DLCO), liters of supplemental oxygen at rest or with exertion, need for ECMO support, or 6-minute walk distance between patients treated with nintedanib or pirfenidone. Five patients on antifibrotic therapy (9.4%) died prior to transplantation [1 nintedanib (4.3%) and 4 pirfenidone (13.3%)]. Nintedanib cessation prior to listing was not associated with increased risk of waitlist death compared to continuation of pirfenidone therapy (Figure, p=0.495). There was no significant difference in waitlist duration between patients on nintedanib (median: 13 days, IQR: 5-26) compared to pirfenidone (21 days, IQR 8-61, p=0.199). Of patients on antifibrotic therapy that underwent transplant (n=48), nintedanib cessation was not associated with increased intra-operative transfusion volume (p=0.852), need for return to operating room for hemorrhage (p=0.164), ICU length of stay (LOS) (p=0.440), or hospital LOS (p=0.646). CONCLUSIONS: Our data show that nintedanib cessation is not associated with increased waitlist mortality in lung transplant candidates with ILD. There were no significant differences in pre- or peri-operative outcomes between waitlisted patients managed with nintedanib cessation compared to continuation of pirfenidone. CLINICAL IMPLICATIONS: Nintedanib cessation in lung transplant candidates is not associated with waitlist mortality. DISCLOSURES: No relevant relationships by Matthew Bacchetta No relevant relationships by Caitlin Demarest No relevant relationships by Ashley Drengler No relevant relationships by David Erasmus No relevant relationships by Alexis Goree No relevant relationships by Eric Lambright No relevant relationships by Katie McPherson no disclosure on file for Stephanie Norfolk; No relevant relationships by Ivan Robbins No relevant relationships by Ciara Shaver no disclosure submitted for Anil Trindade