Comparison of the Efficacy of Pirfenidone and Nintedanib in the Treatment of Patients with Idiopathic Pulmonary Fibrosis—A Single-Center Experience

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive, unpredictable, fatal interstitial lung disease. Antifibrotic therapy with pirfenidone or nintedanib slows functional decline, yet comparative real-world evidence remains limited. Materials and Methods: This retrospective, single-center, comparative cohort study included 76 IPF patients treated at the Clinic for Pulmonology at the University Clinical Center of Serbia (February 2019–February 2025). Diagnosis of IPF was made according to the guidelines of the American Thoracic Society and the European Respiratory Society. Demographic features, comorbidities, forced vital capacity (FVC), diffusion capacity for carbon monoxide (DLCO), high-resolution computerized tomography (HRCT) patterns, 6-min walk test distance (6MWTD), echocardiography, and survival outcomes were analyzed. Disease progression was defined as a ≥10% decline in FVC and/or DLCO after 12 months. Results: Of the 76 patients, 31 received nintedanib and 45 pirfenidone. Baseline characteristics, comorbidities, and HRCT patterns were comparable between groups. Mean annual decline in FVC was −1.74% with pirfenidone and −2.38% with nintedanib, without a statistical difference. DLCO declined by −4.25% and −6.29%, respectively, with similar downward trends over time in both groups. Progression was recorded in 35 (46.1%) patients, of whom 18 (58.06%) were in the nintedanib group and 17 (37.77%) in the pirfenidone group, with no difference between therapies (p = 0.81). Definite and probable usual interstitial pneumonia (UIP) were evenly represented on HRCT, although progression correlated significantly with the probable UIP pattern (p = 0.006). 6MWTD decreased in both groups over 12 months, again without treatment-related differences (p = 0.566). During up to 6 years of follow-up, overall survival was 4.18 years, with no significant difference between the nintedanib (4.55 years) and pirfenidone (3.81 years) groups (p = 0.159). No association was found between disease stage (FVC or DLCO) and progression. Conclusions: This study demonstrates that pirfenidone and nintedanib are equally effective in the management of IPF in real-world settings. The absence of significant differences in functional decline, progression rates, and survival indicates that treatment choices should be guided by individual clinical profiles rather than efficacy alone, reinforcing antifibrotic therapy as the primary approach to alter the course of IPF. Importantly, disease progression was strongly associated with a probable UIP pattern on HRCT, supporting current guidelines suggesting that probable UIP has a natural history and prognosis similar to those of definite UIP.