Effectiveness of a 5-Hydroxytryptamine Type 3 Receptor Antagonist for Treating Nintedanib-Induced Diarrhea: A Prospective Observational Study

<b>Background/Objectives</b>: Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease (ILD) with a poor prognosis. The prognosis of ILDs showing progressive pulmonary fibrosis (PPF) is poor, similar to that of IPF. Diarrhea is the most frequently observed adverse event in ILDs treated with nintedanib. Managing diarrhea is important for maintaining nintedanib use and improving the prognosis of ILDs. <b>Methods</b>: Between October 2022 and March 2025, we enrolled patients with severe nintedanib-induced diarrhea that was uncontrolled by loperamide and/or probiotics. Other drugs were administered to control diarrhea, and the patients were prospectively observed to evaluate stool frequency, stool form score (scores 3, 2, and 1 for watery stool, soft stool without form, and soft stool with form, respectively), quality of life (QOL) using the Japanese version of the irritable bowel syndrome (IBS)-QOL questionnaire, adverse events, and laboratory findings. <b>Results</b>: Eleven patients (IPF, <i>n</i> = 5; PPF, <i>n</i> = 6) were enrolled, and all patients were treated with ramosetron, a 5-hydroxytryptamine type 3 receptor (5-HT₃) antagonist. Ramosetron was terminated within 3 weeks, before sufficient evaluation, because of insufficient efficacy (<i>n</i> = 1) and the discontinuation of nintedanib due to pneumothorax (<i>n</i> = 1). Stool frequency and stool form scores decreased significantly after the initiation of ramosetron therapy; however, IBS-QOL did not improve significantly. IBS-QOL correlated with shortness of breath scores but not with stool frequency. No prominent adverse events were associated with ramosetron administration. <b>Conclusions</b>: Ramosetron, a 5-HT₃ antagonist, improved stool frequency and stool form in patients with severe nintedanib-induced diarrhea.