Pneumologie 2016; 70 - P353
DOI: 10.1055/s-0036-1572001

Consistent effect of nintedanib on decline in FVC in patients across subgroups based on HRCT diagnostic criteria: results from the INPULSIS® trials in idiopathic pulmonary fibrosis (IPF)

M Pfeifer 1, G Raghu 2, A Wells 3, AG Nicholson 3, L Richeldi 4, KR Flaherty 5, F Le Maulf 6, S Stowasser 7, R Schlenker-Herceg 8, DM Hansell 3
  • 1Donaustauf Hospital; presenting on Behalf of the Authors
  • 2University of Washington, Seattle, Washington, USA
  • 3Royal Brompton and Harefield NHS Foundation Trust and National Heart and Lung Institute, Imperial College, London
  • 4National Institute for Health Research Southampton Respiratory Biomedical Research Unit and Clinical and Experimental Sciences, University of Southampton, UK
  • 5University of Michigan Health System, Ann Arbor, Michigan, USA
  • 6Boehringer Ingelheim France S.A.S., Reims, France
  • 7Boehringer Ingelheim Pharma GmbH & Co. Kg, Ingelheim am Rhein
  • 8Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA

Background: The randomized, placebo-controlled, 52-week INPULSIS® trials assessed efficacy and safety of nintedanib 150 mg bid in patients with IPF. Nintedanib significantly reduced annual rate of FVC decline vs. placebo (primary endpoint) in both trials). Key secondary endpoints were time to first acute exacerbation and change from baseline in SGRQ total score, both over 52 weeks.

Methods: If a surgical lung biopsy was unavailable, HRCT criteria A + B + C; or A + C; or B + C had to be met (A = definite honeycombing with basal and peripheral predominance, B = presence of reticular abnormality and traction bronchiectasis consistent with fibrosis with basal and peripheral predominance, C = atypical features absent, specifically nodules and consolidation; ground glass opacity is less extensive than reticular opacity pattern). A post-hoc subgroup analysis of patients with diagnosis based on honeycombing and/or confirmation of UIP by biopsy versus patients with no honeycombing and no biopsy was undertaken using pooled data from both trials.

Results: In patients with honeycombing and/or biopsy, the adjusted annual rate of FVC decline was -108.7 mL/year with nintedanib and -225.7 mL/year with placebo (difference: 117.0 mL/year [95% CI: 76.3, 157.8]); in patients with no honeycombing or biopsy, it was -122.0 mL/year with nintedanib and -221.0 mL/year with placebo (difference: 98.9 mL/year [95% CI: 36.4, 161.5]). The treatment by subgroup interaction p-value was not significant for the primary or key secondary endpoints, indicating that the treatment effect of nintedanib was not statistically significantly different between subgroups.

Conclusion: FVC decline in placebo arms was virtually identical in patients with A) the presence of honeycombing and/or biopsy confirmation of UIP and B) the absence of both, but features of “possible UIP” on HRCT. Nintedanib slowed FVC decline equally in both sub-groups. These findings have major implications for diagnosis and clinical trial design.