CD26/DPP-IV Inhibitors and Associations with Chronic Lung Allograft Dysfunction in a Multicenter Cohort.

Abstract

BACKGROUND CD26/DPP-IV inhibitors (gliptins) target pro-inflammatory pathways that contribute to the development of chronic lung allograft dysfunction (CLAD). We analyzed longitudinal clinical data from 6 North American lung transplant centers to elucidate the effect of gliptin exposure on CLAD development after lung transplantation. METHODS This cohort included 6 North American lung transplant centers, four sites from the Clinical Trials in Organ Transplantation-20 study and 2 additional sites. First lung transplant recipients between December 2015 and August 2018 were eligible with follow up through June 2021. Gliptin exposures prior to CLAD onset in addition to CLAD risk factors were included in the models. The primary endpoint was a composite of probable CLAD, CLAD related deaths, and CLAD related re-transplant. Cox regression models were used to assess the association between gliptin use and the CLAD composite endpoint. RESULTS 779 patients met inclusion criteria, with 126 (16.2%) having any gliptin exposure. 233 (29.9%) patients experienced probable CLAD composite outcome. Across all centers, gliptin exposure at any point was not associated with probable CLAD or definite CLAD across the study period. In a post-hoc analysis of centers with median gliptin exposures > 6 months, exposure within the first 90 days post-transplant was associated with a decreased risk of definite CLAD composite across the study period (HR 0.25; 95% CI, 0.07, 0.83; p<0.05). CONCLUSIONS The association of gliptins and CLAD is complex, but early gliptin use may help protect against CLAD if started within 90 days post-transplant and used for a prolonged period.