Association between serum anti-granulocyte-macrophage colony-stimulating factor autoantibodies and nintedanib-induced...

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.

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.

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).

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.