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A1643 - Risk Factors of Nausea or Anorexia Following Nintedanib Administration in Patients with Idiopathic Pulmonary Fibrosis
Author Block: T. Nakamura, M. Kato, K. Kono, T. Yamada, R. Kanemaru, H. Ihara, T. Sato, N. Harada, S. Togo, T. Nagaoka, F. Takahashi, S. Sasaki, K. Seyama, K. Takahashi; Department of Respiratory Medicine, Juntendo University Graduate School of medicine, Tokyo, Japan.
Rationale Nintedanib is known as the inhibitor of triple tyrosine kinases, including the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) receptors. A phase III trial suggested that treatment with 300 mg/day of nintedanib reduced decline in forced vital capacity (FVC) and acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF). Nausea, anorexia, diarrhea, and liver dysfunction are the most common adverse effects of nintedanib. When a patient with IPF develops these adverse effects, treatment with nintedanib cannot be continued. However, the clinical features of developing nausea or anorexia during nintedanib administration were unknown. We aimed to investigate the toxicity of nintedanib and risk factors for developing nausea or anorexia following nintedanib administration in patients with IPF. Methods We enrolled 52 IPF patients who received nintedanib between October 2015 and September 2017 in this study. The diagnosis of IPF was based on ATS/ERS/JRS/ALAT IPF statement in 2011. We evaluated clinical characteristics, including performance status (PS), respiratory condition, the severity of IPF by both the GAP index and JRS severity at the initiation of nintedanib administration, and the toxicity induced by nintedanib, especially nausea and anorexia. Results The median age of the patients was 72 years; 42 patients were male. Thirty-eight patients exhibited good PS (0-1), and 34 patients presented with smoking history. Twenty-nine patients exhibited high-grade (III-IV) JRS severity upon initiation of nintedanib administration. The GAP index score in 22 patients was over 6. Thirty-seven patients displayed definite usual interstitial pneumonia (UIP) patterns and 18 patients had possible UIP patterns on HRCT. Mean serum KL-6 levels were 1033 ± 560 U/mL. The mean FVC was 2990 ± 720 mL before the initiation of nintedanib administration in all patients. Moreover, the mean decline in FVC in all patients was -30 mL per 6 months. Twelve patients developed nausea or anorexia of above CTCAE grade 2. Of these 12, 7 patients could not receive nintedanib over 6 months owing to this toxicity. There was no significant difference in the decline in FVC between patients with and without nausea or anorexia. Multivariate analysis revealed that low PS and high GAP index were significant risk factors for development of nausea or anorexia due to toxicity of nintedanib. Conclusion Low PS and high GAP index was associated with the development of nausea or anorexia during treatment with nintedanib in patients with IPF.