Outcome after nintedanib therapy for fibrosing interstitial lung disease in patients without dyspnea

Abstract The effectiveness and tolerability of antifibrotic drugs for asymptomatic patients with fibrosing interstitial lung disease (FILD) are unknown. We compared outcomes after starting nintedanib between 17 patients without dyspnea and 56 with dyspnea, adjusting for confounding factors associated with prognosis of FILD. At baseline, there were no significant differences in the incidence of > 4% decrease (69% vs. 89%, P = 0.11) or decrease to < 90% (25% vs. 54%, P = 0.051) in SpO₂ in 6-minute walk test. The incidence of annual progression [defined as > 10% decrease in forced vital capacity (FVC) or 15% decrease in diffusing capacity of lungs for carbon monoxide (DLCO), developing acute exacerbation, or FILD-related death] was significantly lower in non-dyspnea than dyspnea group (18% vs. 52%, adjusted P = 0.044). The relative change in DLCO was significantly slower in non-dyspnea group (adjusted P = 0.044), but FVC was not (adjusted P = 0.079). Overall survival defined by FILD-related death was longer in non-dyspnea group (adjusted P = 0.010). The discontinuation rate and therapeutic period of nintedanib were not significantly different between the two groups. Asymptomatic patients with FILD can have severe exercise-induced hypoxia and better outcome after nintedanib therapy compared with symptomatic patients. Antifibrotic drug therapy should not be avoided solely based on absence of symptoms.