Nintedanib continues to show promise for progressive fibrosing ILDs

Interim analyses of the INBUILD trial presented at ATS 2020 continue to reflect the benefit of the tyrosine kinase inhibitor nintedanib for individuals with progressive fibrosing interstitial lung diseases (ILDs).

The previously reported initial results of INBUILD showed that nintedanib slowed the rate of forced vital capacity (FVC) decline in patients with fibrosing ILDs and a progressive phenotype, with adverse events that were manageable for a majority of the participants. [N Engl J Med 2019;381:1718-1727]

The trial comprised 663 individuals with a fibrosing ILD diagnosis other than idiopathic pulmonary fibrosis, who had shown signs of progression of ILD within 24 months prior to screening. Participants were randomized 1:1 to receive nintedanib 150 mg twice daily or placebo.

Changes in FVC decline

At baseline, mean FVCs were similar between the nintedanib and the placebo arms (68.7% predicted vs 69.3% predicted). [ATS 2020, abstract 710]

At week 52, there were fewer nintedanib vs placebo recipients who had an absolute decline in FVC >5% predicted (43 percent vs 55 percent; odds ratio [OR], 0.63, 95 percent confidence interval [CI], 0.46–0.85) and in FVC >10% predicted (28 percent vs 37 percent; OR, 0.68, 95 percent CI, 0.49–0.95).

A similar trend in favour of nintedanib over placebo was seen in terms of relative decline in FVC >5% predicted (52 percent vs 69 percent; OR, 0.50, 95 percent CI, 0.36–0.68) and in FVC >10% predicted (41 percent vs 49 percent; OR, 0.70, 95 percent CI, 0.52–0.96).

“[These findings show that] the proportions of patients with declines in FVC >5% predicted and >10% predicted over 52 weeks were lower with nintedanib vs placebo. These results support the benefit of nintedanib on slowing the progression of fibrosing ILD,” said the researchers.

Overall, the difference between nintedanib and placebo in terms of adjusted annual rate of FVC decline was 107.0 (95 percent CI, 65.4–148.5). [ATS 2020, abstract 709]

On subgroup analysis, the differences in adjusted annual rates of FCV decline between nintedanib and placebo were as follows: 145.2 and 64.2 (male and female), 86.9 and 115.1 (<65 and ≥65 years), 110.6 and 93.0 (Whites and Asians), 91.7 and 130.0 (≤70% and >70% predicted), 73.1 (hypersensitivity pneumonitis), 104.0 (autoimmune ILDs), 141.6 (iNSIP*), 68.3 (unclassifiable IIP**), and 197.1 (other fibrosing ILDs).

These figures imply that nintedanib had a consistent effect in terms of reducing the annual rate of FVC decline across patient subsets regardless of demographic characteristics, lung function, or ILD diagnosis, noted the researchers.

Patient-reported outcomes

When assessing the impact of nintedanib on symptoms and health-related quality of life (HRQoL), statistically significant differences between nintedanib and placebo were seen in terms of L-PF*** scores (adjusted mean absolute change from baseline, –4.1; p<0.0001 [total], –3.5; p=0.008 [dyspnoea], and –6.1; p=0.0008 [cough]) at week 52. [ATS 2020, session B16]

Adjusted mean changes in PF-IQOLS^# summary score also favoured nintedanib over placebo (0.08 vs 0.20; difference, −0.12, 95 percent CI, −0.23 to −0.01; p=0.04).

“[The] results obtained using the L-PF questionnaire suggested that nintedanib may prevent worsening of cough and … dyspnoea, while … the PF-IQOLS [scores] suggested that nintedanib may reduce worsening of HRQoL,” said the researchers.