Abstract:

Objective

To analyze the tolerability and efficacy predictors of nintedanib （NT） in the treatment of idiopathic pulmonary fibrosis （IPF）.

Methods

Prospective inclusion of 67 patients with IPF between March 2020 and December 2023， all patients were the initial measurement of 300 mg of NT treatment，and （in group） on the day before treatment， chest CT scan and lung function test were performed before treatment （the day of enrollment） and at 6 months （M） and 12 M treatment. The occurrence of adverse events in IPF patients was recorded.

Results

A total of 45（67.16%） IPF patients experienced a reduction in NT dose during 12 M，of which 34 patients experienced a reduction within 6 M，and the reason for this reduction in all patients NT dose are adverse events happened， a total of 20（29.85%） IPF patients stopped NT within 12 M， and 10 of them stopped NT within 6 M， Adverse events were the most common reason for discontinuation in our study. IPF patients ≥75 years old had a higher incidence of dose reduction during 6 M， and most patients discontinued NT because of the occurrence of adverse events （P ＜0.05）. According to the LASSO and multiariable Logistic regression analysis， the female， forced vital capacit to the predicted value （FVC% pre）＜76.70%， surfactant protein D （SP-D）≥263.50 ng/ml for IPF patients 12 M NT independent risk factors for the development of drug discontinuation， The area under the receiver operating characteristic curve of risk score［1× （female） +1× （FVC%pre＜76.70%） +1× （SP-D≥263.50 ng/ml）］ for predicting the discontinuation of NT therapy within 12 M in IPF patients was 0.760 （95%CI： 0.688-0.822）. FVC decline in IPF patients with continued NT therapy was significantly less than that in patients with discontinued NT therapy ［0.03（-0.16，0.27）L vs. -0.14（-0.50， 0.07）L， Z=-2.405， P=0.016］. FVC change was negatively correlated with body mass index （BMI） （Rho=0.410， P＜0.001） and FVC%pre （Rho=0.427， P＜0.001）.

Conclusion

The results of this study showed that the main causes of NT dose reduction and NT discontinuation in IPF patients during 12 M were adverse events， according to gender， FVC% pre， SP-D design can predict the risk of 12 M NT drug discontinuation. In addition， patients who continued NT therapy during the 12 M period had less decline in FVC than those who discontinued NT therapy， and FVC changes were related to BMI and FVC%pre.

Key words: Idiopathic pulmonary fibrosis, Nintedanib, Tolerance, Efficacy predictio