Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study

Yusuke Ushio; Risa Wakiya; Tomohiro Kameda; Shusaku Nakashima; Hiromi Shimada; Taichi Miyagi; Koichi Sugihara; Rina Mino; Mao Mizusaki; Kanako Chujo; Ryoko Kagawa; Hayamasa Yamaguchi; Norimitsu Kadowaki; Hiroaki Dobashi

doi:10.1186/s41927-024-00400-y

Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study

BMC Rheumatol. 2024 Jun 18;8(1):27. doi: 10.1186/s41927-024-00400-y.

Affiliations

¹ Faculty of Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita- gun, Kagawa, Kagawa, 761-0793, Japan.
² Faculty of Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita- gun, Kagawa, Kagawa, 761-0793, Japan. wakiya.risa@kagawa-u.ac.jp.

Abstract

Background: In 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS).

Methods: CTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups.

Results: Twenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups.

Conclusions: This study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD.

Keywords: Antifibrotic therapy; Connective tissue disease (CTD); Interstitial lung disease (ILD); Nintedanib; Progressive fibrosing interstitial lung disease (PF-ILD).