Nintedanib slows course of interstitial lung disease in Asians

Use of nintedanib in the treatment of interstitial lung disease (ILD) appears to delay its progression in Japanese patients, independent of the fibrotic pattern on high-resolution computed tomography (HRCT), as shown in a subgroup analysis of the phase III INBUILD trial.

In the subgroup of 108 Japanese patients with fibrosing ILDs, the annual rate of decline in forced vital capacity (FVC) over 52 weeks—the primary efficacy endpoint—was significantly lower among those who received twice-daily 150-mg nintedanib (n=52) vs placebo (n=56; −148.31 vs −240.36 mL/year; adjusted difference, 92.05 mL/year). [Respir Med 2021;187:106574]

“Despite the differences in baseline clinical characteristics, the effect of nintedanib on efficacy endpoints in Japanese patients with progressive fibrosing ILDs was consistent with those of non-Japanese patients [adjusted difference, 110.24 mL/year],” according to the investigators. [BMJ Open Respir Res 2017;4e000212;]

“The treatment-by-subgroup interaction p-values ranged from 0.5605 to 0.8892, suggesting there was no heterogeneity in treatment effects between Japanese and non-Japanese patients regardless of the fibrotic pattern [usual interstitial pneumonia-like or others] on HRCT,” they added.

The lung function decline-slowing benefit with nintedanib occurred alongside other clinically meaningful outcome measures. Compared with placebo, the study drug conferred lower risks of acute exacerbation or death (hazard ratio [HR], 0.30, 95 percent confidence interval [CI], 0.10–0.91) and mortality (HR, 0.54, 95 percent CI, 0.14–2.11) in Japanese patients.

There were no new or unexpected safety findings, with the safety profile of nintedanib in line not only with those of non-Japanese patients but also with those of the overall INBUILD population and a pooled analysis of patients with idiopathic pulmonary fibrosis (IPF) from six clinical trials, which showed a higher rate of diarrhoea and liver enzyme elevations with active treatment vs placebo. [N Engl J Med 2019;381:1718-1727; BMJ Open Respir Res 2019;6e000397]

However, it is worth noting that more Japanese than non-Japanese patients developed serious adverse events (AEs), regardless of treatment. Furthermore, in the nintedanib treatment group, AEs that led to permanent dose reduction were higher while AEs that resulted in death in the nintedanib group were lower in the Japanese cohort than in the non-Japanese cohort.

“Although some AEs occurred more frequently compared with the overall INBUILD population, the safety profile of nintedanib was consistent with Japanese patients in previous trials of patients with IPF and systemic sclerosis-associated ILD,” the investigators pointed out. [Respirology 2017;22:750-757; Mod Rheumatol 2021;31:141-150]

“Collectively, these findings provide clinicians with assurances regarding the efficacy and safety of nintedanib in Japanese patients with progressive fibrosing ILDs,” they added.