Respiratory Trials·org

Interstitial lung disease · Antifibrotics beyond IPF

INBUILD subgroups subgroup analysis

Nintedanib in progressive fibrosing ILD: subgroup analyses by ILD diagnosis

INBUILD subgroups trial design and results
Design Prespecified subgroup analysis of a double-blind, placebo-controlled phase 3 trial
Treatment Nintedanib 150 mg twice daily
Control Placebo
Population 663 participants of INBUILD: 173 (26%) chronic hypersensitivity pneumonitis, 170 (26%) autoimmune ILD, 125 (19%) idiopathic non-specific interstitial pneumonia, and others
Follow-up 52 weeks
Primary endpoint Rate of FVC decline within each ILD diagnostic subgroup
Result Of 663 participants, 173 (26%) had chronic hypersensitivity pneumonitis, 170 (26%) an autoimmune ILD, 125 (19%) idiopathic non-specific interstitial pneumonia, 114 (17%) unclassifiable idiopathic interstitial pneumonia and 81 (12%) other ILDs. The effect on FVC decline was consistent in direction across all five: 73.1 mL/year (95% CI -8.6 to 154.8) in hypersensitivity pneumonitis, 104.0 (21.1 to 186.9) in autoimmune ILD and 141.6 (46.0 to 237.2) in idiopathic NSIP. The trial was not powered for any individual subgroup.
Secondary endpoints Adverse events by subgroup

The INBUILD trial was not designed or powered to provide evidence for a benefit of nintedanib in specific diagnostic subgroups. However, its results suggest that nintedanib reduces the rate of ILD progression, as measured by FVC decline, in patients who have a chronic fibrosing ILD and progressive phenotype.

The trial authors, in the published abstract

How it has aged

Exemplary caution from the authors: they state in the abstract that the trial cannot prove subgroup benefit, and the finding is consistency of direction rather than significance within any diagnosis. That is precisely the right way to read it, and it is why guidelines treat progressive fibrosing ILD as one entity. See INBUILD.

Publications

Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial

Wells AU, Flaherty KR, Brown KK, et al. Nintedanib in patients with progressive fibrosing interstitial lung diseases-subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet Respir Med 2020 May;8(5):453-460.

  • Consistent direction of effect across hypersensitivity pneumonitis, autoimmune ILD and idiopathic NSIP
  • No individual subgroup was powered to demonstrate benefit