POS0885 NINTEDANIB COMBINED WITH IMMUNOSUPPRESSIVE AGENTS INCREASED FORCED VITAL CAPACITY IN CONNECTIVE TISSUE DISEASE-ASSOCIATED PF-ILD: A SINGLE-CENTER STUDY IN JAPAN
Authors: Y. Ushio, R. Wakiya, S. Nakashima, T. Miyagi, K. Sugihara, M. Mizusaki, R. Kagawa, H. Yamaguchi, H. Shimada, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Japanese patients with connective tissue diseases (CTD) are frequently complicated by interstitial lung disease (CTD-ILD) and many patients with CTD-ILD were treated with various immunosuppressive agents (IS). Recently, nintedanib (NTB), a multitargeted tyrosine kinase inhibitor, has been approved for the treatment of progressive fibrosing ILD (PF-ILD) including CTD-ILD. However, the efficacy of combination therapy with NTB and IS for CTD-associated PF-ILD (CTD-PF-ILD) is unclear. <h3>Objectives:</h3> We aimed to clarify the efficacy and safety of the NTB treatment combined with IS for CTD-PF-ILD in real clinical practice. <h3>Methods:</h3> CTD-PF-ILD patients who received NTB at our institution between May 1, 2020 and September 30, 2023, and who underwent pulmonary function tests (PFT) before and after NTB treatment were included in this retrospective study. The patients were required to meet the criteria for PF-ILD [1]. To clarify the efficacy and safety of NTB treatment combined with IS for CTD-PF-ILD, patients were divided into two groups: one in which NTB alone was added (NTB group) and the other in which NTB and IS were added (NTB+IS group). Changes before and after NTB treatment in pulmonary function (FVC (%), FVC (mL), DLCO (%)) and serum Krebs von den Lungen-6 (KL-6), reported as a biomarker of disease activity in CTD-ILD, and the incidence of adverse events (AEs) during NTB treatment were investigated and compared between the two groups using the Wilcoxon rank-sum test and Fisher's exact test. All p values were 2-sided, and a p value &lt;0.05 was considered significant. <h3>Results:</h3> Twenty-six patients with CTD-PF-ILD were included in this study. Patient characteristics are shown in Table 1. After the diagnosis of CTD-PF-ILD, NTB alone was added in 15 of the 26 patients (NTB group), and NTB plus IS were added in 11 patients (NTB+IS group). Among the 11 participants in the NTB+IS group, the most common additional IS was rituximab (RTX) in 6 participants (54.6%), followed by GC in 4 participants (36.4%). After NTB treatment, FVC (%) and FVC (mL) increased slightly (not statistically significant) and FVC (%/M) improved significantly (Figure 1). In comparison between the NTB group and the NTB+IS group, ⊿FVC (%), ⊿FVC (mL), ⊿FVC (%/M) were all significantly greater in the NTB+IS group than NTB group (Figure 1). Mean KL-6 (U/mL) in all patients decreased from 1240.1 U/mL to 964.4 U/mL, and ⊿KL-6 (U/mL) was significantly greater in the NTB+IS group than NTB group (-490.1 U/mL vs. -118.5 U/mL, p=0.0059). A significant negative correlation was observed between ⊿KL-6 (U/mL) and ⊿FVC (%) (ρ=-0.6620, p=0.0002). As for AEs, fourteen patients (53.9%) had diarrhea, two (7.7%) had elevated liver enzymes, one (3.9%) had nausea, and one (3.9%) had headache. The dose of NTB was reduced in 11 patients (42.3%), mainly due to diarrhea. There was no difference in the incidence of AEs between the two groups. <h3>Conclusion:</h3> This study suggested the NTB treatment combined with IS may be more effective for CTD-PF-ILD in preventing the reduction of FVC than NTB monotherapy. Furthermore, NTB combined with IS may be a potential to increase FVC in patients with CTD-PF-ILD. <h3>REFERENCES:</h3> [1] Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. 2019;381:1718-1727. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>