Association of PDGFRB, VEGFR2, and TGFB1 Gene Polymorphisms with Nintedanib Efficacy and Adverse Effects in Patients with Progressive Pulmonary Fibrosis.

Progressive pulmonary fibrosis (PPF) comprises interstitial lung diseases characterized by progressive fibrosis and lung function decline. Nintedanib slows disease progression by inhibiting FGFR, VEGFR, and PDGFR signaling, but treatment response varies among patients. We investigated whether VEGFR2, PDGFRB, and TGFB1 gene variants are associated with nintedanib treatment outcomes, including changes in pulmonary function, diffusing capacity and adverse effects. This prospective study included 75 patients with PPF diagnosed according to ATS/ERS/JRS/ALAT criteria and treated with nintedanib at the Clinic of Pulmonology, University Clinical Center of Serbia. Spirometry and diffusing capacity were assessed at baseline and after 6 and 12 months. Genotyping of VEGFR2 rs2071559 and rs1870377; PDGFRB rs2302273, rs2229562, and rs246395; and TGFB1 rs1800470 was performed using TaqMan® assays. Carriers of the PDGFRB rs2302273 A allele more frequently experienced gastrointestinal adverse events (45.2% vs. 20.5%; p = 0.022; OR 3.2, 95% CI 1.156-8.866) and diarrhea (38.7% vs. 15.9%; p = 0.026; OR 3.3, 95% CI 1.129-9.869). Patients with the PDGFRB rs246395 TT genotype more frequently had a ≥15% decline in DLCO after one year (46% vs. 22%; p = 0.038; OR 3.0, 95% CI 1.045-8.394). No significant associations were observed for the analyzed VEGFR2 or TGFB1 variants. These findings suggest that PDGFRB variants may be associated with nintedanib treatment outcomes, although confirmation in larger cohorts is needed.