Association between serum anti-granulocyte-macrophage colony-stimulating factor autoantibodies and nintedanib-induced diarrhea in interstitial lung disease: a retrospective study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and non-IPF interstitial lung diseases (ILDs) with progressive pulmonary fibrosis (PPF) are associated with poor prognosis. Nintedanib slows the decline in forced vital capacity (FVC) and improves survival; however, diarrhea is the most common adverse event and often leads to treatment discontinuation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has protective effects on intestinal epithelial integrity, whereas anti-GM-CSF autoantibodies (GMAb) have been associated with disease activity in inflammatory bowel diseases (IBDs). This study aimed to evaluate the utility of serum GMAb levels as a predictor of nintedanib-induced diarrhea. METHODS: Forty-one patients with ILDs treated with nintedanib were included. Diarrhea within 3 months of treatment initiation was retrospectively assessed using structured interviews. Predictive factors were analyzed using univariate and multivariate logistic regression models, including relevant clinical variables. RESULTS: The cohort included 30 male patients with underlying diagnoses of IPF (n=26) and non-IPF ILDs meeting PPF criteria (n=15). Diarrhea within 3 months occurred in 26 patients. Male sex was significantly associated with diarrhea (P=0.036), whereas IPF showed a trend toward association (P=0.096). Serum GMAb levels >0.77 µg/mL were independently associated with diarrhea after adjustment for ILD type, sex, and nintedanib dose normalized by body surface area (BSA, multivariate logistic regression). CONCLUSIONS: Elevated serum GMAb levels might serve as a predictor of nintedanib-induced diarrhea. GM-CSF/GMAb-related pathways might be associated with the pathogenesis of nintedanib-induced diarrhea. However, validation with a large-scale study is needed to show the clinical and pathophysiological role of GMAb in the future.