Differences in Tolerability of Antifibrotic Agents Between Connective Tissue Disease-Associated and Non-connective Tissue Disease-Associated Interstitial Lung Disease.

Background Although antifibrotic agents (AFAs) are often discontinued due to side effects, their tolerability is crucial given the limited treatment options for interstitial lung disease associated with connective tissue disease (CTD-ILD). The possibility of intolerance due to organ damage caused by CTDs has also been considered; however, few detailed studies are available. We hypothesized that AFAs for CTD-ILD would be poorly tolerated or discontinued prematurely due to organ damage caused by collagen disease. Therefore, we conducted a retrospective investigation to explore this hypothesis. Methods We retrospectively reviewed the medical records of ILD patients treated with nintedanib or pirfenidone at St. Luke's International Hospital between December 2008 and November 2022, comparing the CTD-ILD group with the non-CTD-ILD group. Patient background, cumulative discontinuation rate due to adverse events (AEs), duration of prescription until discontinuation, AEs leading to discontinuation, and mortality rate were collected from medical records. Results We identified 42 and 129 patients in the CTD-ILD and non-CTD-ILD groups, respectively. The cumulative incidence of discontinuation due to AEs did not significantly differ between the CTD-ILD and non-CTD-ILD groups in the overall population or when restricted to nintedanib and pirfenidone (overall population, p = 0.402; nintedanib group, p = 0.510; pirfenidone group, p = 0.625). The duration of AFA use at discontinuation due to AEs was not significantly different between the overall group (CTD-ILD vs. non-CTD-ILD, median: 77 vs. 116 days, p = 0.496) and the pirfenidone group (CTD-ILD vs. non-CTD-ILD, median: 136 vs. 55 days, p = 0.127). However, for nintedanib, the duration in the CTD-ILD group was significantly shorter than that in the non-CTD-ILD group (median: 23 vs. 218 days, p = 0.016). Gastrointestinal symptoms were the most common reason for discontinuation. Of the seven cases of CTD-ILD patients who used nintedanib and discontinued due to AEs, six were female, four had systemic sclerosis (SSc), and three were using tacrolimus. Conclusions The cumulative incidence of discontinuations due to AEs did not significantly differ between the CTD-ILD and non-CTD-ILD groups. However, the duration of nintedanib use was significantly shorter in the CTD-ILD group when the discontinuation was due to AEs. Particularly, when administering nintedanib to patients with SSc and/or those using tacrolimus, measures to prevent AEs should be carefully implemented.