Nintedanib in patients with idiopathic pulmonary fibrosis and preserved lung volume

Abstract

Rationale: There is no consensus as to when treatment for idiopathic pulmonary fibrosis (IPF) should be initiated. Some physicians prefer not to treat patients with preserved lung volume.

Objective: To investigate whether patients with IPF and preserved lung volume receive the same benefit from nintedanib as patients with more impaired lung volume.

Methods: Post hoc subgroup analyses of pooled data from the two replicate phase III INPULSIS trials by baseline FVC % predicted (≤90%, >90%).

Results: At baseline, 274 patients had FVC >90% predicted and 787 patients had FVC ≤90% predicted. In patients treated with placebo, the adjusted annual rate of decline in FVC was consistent between patients with FVC >90% predicted and FVC ≤90% predicted (-224.6 mL/year and -223.6 mL/year, respectively). There was no statistically significant difference between these subgroups in the effect of nintedanib on annual rate of decline in FVC, change from baseline in St George's Respiratory Questionnaire total score or time to first acute exacerbation. In patients with baseline FVC >90% predicted and ≤90% predicted, respectively, the adjusted annual rate of decline in FVC with nintedanib was -91.5 mL/year (difference vs placebo: 133.1 mL/year (95% CI 68.0 to 198.2)) and -121.5 mL/year (difference vs placebo: 102.1 mL/year (95% CI 61.9 to 142.3)). Adverse events associated with nintedanib were similar in both subgroups.

Conclusions: Patients with IPF and preserved lung volume (FVC >90% predicted) have the same rate of FVC decline and receive the same benefit from nintedanib as patients with more impaired lung volume.

Trial registration number: NCT01335464 and NCT01335477.

Keywords: Idiopathic pulmonary fibrosis.

Conflict of interest statement

Competing interests: MK reports receipt of grants and personal fees from Boehringer Ingelheim and Roche; personal fees from GlaxoSmithKline, Gilead, AstraZeneca, ProMetic and Genoa; and grants from Actelion, Respivert, the Canadian Institute for Health Research and the Canadian Pulmonary Fibrosis Foundation. LR reports receipt of grants and personal fees from Boehringer Ingelheim for being a member of the INPULSIS steering committee and co-principal investigator of the trials; grants and personal fees from InterMune for being a member of an advisory board; personal fees from MedImmune (advisory board member), Biogen Idec (consulting), Sanofi-Aventis (consulting), Roche (advisory board member), Takeda (advisory board member), ImmuneWorks (consulting), Shionogi (speaker honoraria) and GlaxoSmithKline (advisory board member). JB reports serving as an ILD expert for the current international IPF guidelines; serving as Chair or member of the steering committees for the Panorama, BUILD-3, Artemis-IPF, Artemis-PH and RISE-IIP clinical trials; receipt of grants and personal fees from Actelion and InterMune; and personal fees from Boehringer Ingelheim, Grünenthal, Gilead, Bayer, Roche and GlaxoSmithKline. TMM reports receipt of grants and personal fees from GlaxoSmithKline (advisory board member); grants from Novartis; grants and non-financial support from UCB; non-financial support from Takeda; personal fees from Boehringer Ingelheim, InterMune, Lanthio, Sanofi-Aventis, AstraZeneca, Roche, Bayer, Biogen Idec, Cipla, DOSA, ProMetic and Galapagos; and serving as an investigator in an ongoing Gilead phase 2b study. WT, SSt and CH are employees of Boehringer Ingelheim. RMdB has served as a steering committee member for Boehringer Ingelheim and InterMune, and as an advisory board member for GlaxoSmithKline and Actelion.

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Figures

Figure 1

Adjusted annual rate (SE) of decline in FVC (mL/year) by subgroup.

Figure 2

Time to absolute decline in FVC ≥10% predicted or death over 52 weeks by subgroup. HR was 0.59 (95% CI 0.38 to 0.89) in patients with baseline FVC >90% predicted and 0.61 (95% CI 0.48 to 0.78) in patients with baseline FVC ≤90% predicted. Treatment-by-subgroup interaction p=0.830.

Figure 3

Time to absolute decline in FVC ≥5% predicted or death over 52 weeks by subgroup. HR was 0.67 (95% CI 0.50 to 0.90) in patients with baseline FVC >90% predicted and 0.59 (95% CI 0.49 to 0.71) in patients with baseline FVC ≤90% predicted. Treatment-by-subgroup interaction p=0.486.

Figure 4

Time to first acute exacerbation over 52 weeks by subgroup. HR was 0.46 (95% CI 0.09 to 2.48) in patients with baseline FVC >90% predicted and 0.66 (95% CI 0.39 to 1.11) in patients with baseline FVC ≤90% predicted. Treatment-by-subgroup interaction p=0.956.