LONG-TERM FUNCTIONAL TRAJECTORIES AND TREATMENT RETENTION WITH NINTEDANIB IN IPF AND PROGRESSIVE SARD-ILD

Nintedanib is an antifibrotic treatment for idiopathic pulmonary fibrosis (IPF) and has also demonstrated efficacy in progressive fibrosing interstitial lung diseases (ILDs). However, real-world data on longitudinal functional trajectories and long-term treatment persistence in systemic autoimmune rheumatic disease-associated ILD (SARD-ILD) with a progressive pulmonary fibrosis phenotype remain limited. This study aimed to evaluate longitudinal pulmonary function and long-term nintedanib treatment persistence in patients with IPF and progressive SARD-ILD/PPF in routine clinical practice. Methods This multicenter retrospective study included 274 adults treated with nintedanib: 136 patients with IPF and 138 with progressive SARD-ILD/PPF. Longitudinal changes in percentage-predicted forced vital capacity (ppFVC), total lung capacity (ppTLC), and diffusing capacity for carbon monoxide (ppDLCO) were assessed using linear mixed-effects models adjusted for age and sex, with time considered as a continuous variable and patient-specific random intercepts. Differences in longitudinal trajectories between diagnostic groups were assessed using time-by-condition interaction terms. Treatment persistence was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Death was subsequently considered as a competing event for treatment discontinuation, with cumulative incidence compared using Gray’s test and predictors of discontinuation assessed using multivariable Fine–Gray regression. Results Functional follow-up was available for 129 patients with IPF and 126 with SARD-ILD/PPF. In IPF, ppFVC and ppTLC remained stable over time, whereas ppDLCO showed a significant decline (−0.289 percentage points/month, 95% CI −0.376 to −0.203; p<0.001). In SARD-ILD/PPF, no significant longitudinal changes were observed in ppFVC (−0.075/month; p=0.21), ppTLC (−0.004/month; p=0.96), or ppDLCO (−0.049/month; p=0.36). The ppDLCO trajectory differed significantly between groups, with a more favorable slope in SARD-ILD/PPF than in IPF (time-by-condition interaction +0.235 percentage points/month, 95% CI 0.100–0.371; p<0.001). Treatment persistence was high during the first year, with estimated retention of 95.8% in IPF and 91.9% in SARD-ILD/PPF. At five years, estimated retention was 69.5% and 77.6%, respectively, although estimates were subject to increasing uncertainty because of the limited number of patients remaining under observation. The unadjusted competing-risk comparison of treatment discontinuation did not reach statistical significance (Gray’s test, p=0.058). However, in multivariable Fine–Gray analysis, SARD-ILD/PPF was associated with a higher subdistribution hazard of nintedanib discontinuation compared with IPF (sHR 1.66, 95% CI 1.08–2.55; p=0.021). Conclusions: In this multicenter real-world cohort, lung volumes remained broadly stable over time in both IPF and progressive SARD-ILD/PPF patients treated with nintedanib, while ppDLCO declined significantly in IPF but remained stable in SARD-ILD/PPF. This finding may reflect differences in the underlying pathophysiology and disease trajectories of IPF and SARD-ILD/PPF, which may contribute to the distinct patterns of functional evolution observed in the two groups. However, given the observational design of the study, these findings should not be interpreted as evidence of a differential treatment effect of nintedanib. Treatment persistence was high during the first year and remained substantial during long-term follow-up, although adjusted competing-risk analysis suggested a higher subdistribution hazard of discontinuation in SARD-ILD/PPF. These findings provide complementary real-world evidence on longitudinal functional trajectories and treatment persistence in patients with fibrotic ILDs treated with nintedanib. Further prospective studies with longer follow-up and systematic assessment of treatment tolerability and dose modifications are warranted to better characterize long-term treatment persistence and functional outcomes.