Significance of clinical parameters and biomarkers to predict nintedanib-induced diarrhea: an interview-based retrospective study

Sep 30, 2026

Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis are associated with poor prognosis, and nintedanib-treated patients can experience nintedanib-induced diarrhea, sometimes leading to treatment discontinuation. This interview-based retrospective study aimed to identify clinical predictors of nintedanib-induced diarrhea and to clarify the added significance of interstitial lung disease biomarkers after adjusting for those clinical predictors. Seventy-nine nintedanib-treated ILD patients were analyzed with logistic regression, including serum SP-D and peripheral blood monocyte counts.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Background

Methods

Patients and data collection

Statistical analyses

Results

Participant characteristics

Predictors of diarrhea

Biomarker associations

Conclusions

Clinical implications

Significance of clinical parameters and biomarkers to predict nintedanib-induced diarrhea: an interview-based retrospective study Toru Arai1^, Masakazu Hiramatsu2,3, Naoko Takeuchi4, Takayuki Takimoto1, Tomoko Kagawa4, Ryota Shintani5, Mitsuhiro Moda4, Masaki Hirose1, Tamaki Nakayama6, Yoko Yasui3 1Clinical Research Center, NHO Kinki Chuo Chest Medical Center, Sakai City, Osaka, Japan; 2Department of Nutrition and Dietetics, Faculty of Nutrition, Tokyo Kasei University, Tokyo, Japan; 3Department of Nutrition Graduate School of Human Life and Ecology, Osaka Metropolitan University, Osaka City, Japan; 4Department of Respiratory Medicine, NHO Kinki Chuo Chest Medical Center, Sakai City, Osaka, Japan; 5Department of Rehabilitation, NHO Kinki Chuo Chest Medical Center, Sakai City, Osaka, Japan; 6Department of Clinical Nutrition, NHO Kinki Chuo Chest Medical Center, Sakai City, Osaka, Japan Contributions: (I) Conception and design: T Arai, M Hiramatsu, T Nakayama, Y Yasui; (II) Administrative support: T Nakayama, Y Yasui; (III) Provision of study materials or patients: T Nakayama, T Arai, N Takeuchi, T Takimoto, T Kagawa, R Shintani, M Moda; (IV) Collection and assembly of data: T Nakayama; (V) Data analysis and interpretation: T Arai, M Hiramatsu, M Hirose; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Toru Arai, MD, PhD. Executive Director, Clinical Research Center, NHO Kinki Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555, Japan. Email: [toarai1192296@gmail.com](toarai1192296@gmail.com). Background: Idiopathic pulmonary fibrosis (IPF) is a poor prognostic fibrotic interstitial lung disease (ILD) of unknown etiology. Similarly, the prognosis of patients with ILD and progressive pulmonary fibrosis (PPF) is poor. Nintedanib reduces the decline in forced vital capacity (FVC) and improves the survival of patients with IPF and non-IPF ILDs meeting PPF criteria (hereafter “PPF”) . Diarrhea is a significant adverse event associated with nintedanib, and it is sometimes the reason for the discontinuation of the drug. In this study, we aimed to identify clinical predictors of nintedanib-induced diarrhea and to clarify significance of ILD biomarkers to predict their occurrence after the adjustment using the significant clinical predictors. Methods: Seventy-nine patients with ILDs treated with nintedanib were included in this study. Diarrhea was retrospectively evaluated based on interviews, and medical records were reviewed for other clinical findings. Furthermore, biomarkers including surfactant protein-D (SP-D) serum levels and peripheral blood monocyte counts were examined. Parameters’ predictive abilities were examined using univariate and multivariate logistic regression analyses. Results: Participants comprised 57 males and 22 non-smokers. The underlying ILDs included IPF (n=39) and PPF (n=40) . PPF included idiopathic interstitial pneumonia (IIP) other than IPF (n=19), fibrotic hypersensitivity pneumonitis (FHP) (n=8), connective tissue disease-related ILDs (CTD-ILDs) (n=8), and other ILDs (n=5) . Fourteen patients underwent corticosteroid therapy at the initiation of nintedanib. Nintedanib-induced diarrhea occurred within 3 months in 47 patients (IPF, n=30; PPF, n=17) . IPF, no corticosteroid therapy, nintedanib per body surface area (BSA), and %FVC ≤80% were associated with the occurrence of diarrhea within 3 months after commencing nintedanib treatment by multivariate logistic regression analysis. Additionally, monocyte counts ≤650/μL and serum SP-D >157.5 ng/mL were associated with occurrence of diarrhea after the adjustment of other factors. Conclusions: Nintedanib-induced diarrhea is significantly associated with various complex factors. IPF, no corticosteroid therapy, a higher nintedanib dose per BSA, and a lower %FVC were associated with the ^ ORCID: 0000-0002-2222-0683. © AME Publishing Company. J Thor

FAQs

What was the study designed to determine about nintedanib-induced diarrhea?

The study aimed to identify clinical predictors of nintedanib-induced diarrhea and assess the significance of ILD biomarkers for predicting its occurrence after adjusting for those predictors.

How was diarrhea evaluated in the study?

Diarrhea was retrospectively assessed through interviews, with medical record review for other clinical findings.

Which biomarkers were examined for their association with diarrhea?

Serum surfactant protein-D (SP-D) levels and peripheral blood monocyte counts were measured and analyzed for predictive associations.

Sep 30, 2026

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