CD26/DPP-IV inhibitors and associations with chronic lung allograft dysfunction in a multicenter cohort.

BACKGROUND: CD26/dipeptidyl peptidase 4 inhibitors (gliptins) target proinflammatory 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, 4 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 before CLAD onset, in addition to CLAD risk factors, were included in the models. The primary end-point was a composite of probable CLAD, CLAD-related deaths, and CLAD-related retransplant. Cox regression models were used to assess the association between gliptin use and the CLAD composite end-point. RESULTS: Seven hundred and seventy-nine patients met inclusion criteria, with 126 (16.2%) having any gliptin exposure. Two hundred and thirty-three (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 posthoc 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 (hazard ratio [HR] 0.25; 95% confidence interval [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.

Duke Scholars

Author Laurie D. Snyder Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Megan Lee Neely Biostatistics & Bioinformatics, Division of Biostatistics

Author Alexander Robert Thomas Graham Medicine, Pulmonary, Allergy, and Critical Care Medicine