Introduction: CA-125 is a biomarker of epithelial injury that has been associated with the progression of fibrosing ILD in adults. Little is known about circulating biomarkers in children and adolescents with fibrosing ILD.

Aim: To investigate changes in biomarkers in children and adolescents with fibrosing ILD treated with nintedanib.

Methods: Patients aged 6?17 years with clinically significant fibrosing ILD were enrolled in the InPedILD trial. Patients were randomised 2:1 to receive nintedanib or placebo double-blind for 24 weeks. Fold changes from baseline in adjusted mean levels of CA-125and lactate dehydrogenase (LDH), a marker of lung inflammation, were analysed at week 24. Data were log₁₀ transformed before analysis and estimates of change from baseline were back-transformed.

Results: Mean (SD) CA-125 levels at baseline were 19.8 (14.8) and 18.9 (13.5) U/mL in the nintedanib (n=25) and placebo (n=13) groups, respectively. Fold changes from baseline in adjusted mean (95% CI) CA-125 at week 24 were 0.82 (0.73, 0.91) U/mL in the nintedanib group (n=21) and 0.90 (0.77, 1.05) U/mL in the placebo group (n=11) (ratio 0.91 [0.75, 1.10]). Mean (SD) LDH levels at baseline were 253.9 (90.1) and 228.4 (83.7) U/L in the nintedanib (n=25) and placebo (n=12) groups, respectively. Fold changes from baseline in adjusted mean (95% CI) LDH at week 24 were 0.97 (0.91, 1.04) U/L in the nintedanib group (n=21) and 0.97 (0.88, 1.08) U/L in the placebo group (n=9).

Conclusion: Data from the InPedILD trial suggest that in children and adolescents with fibrosing ILD, treatment with nintedanib is associated with nominal reductions in CA-125 but not LDH over 24 weeks.