Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis

Stéphane Jouneau, Bruno Crestani, Ronan Thibault, Mathieu Lederlin, Laurent Vernhet, Claudia Valenzuela, Marlies Wijsenbeek, Michael Kreuter, Wibke Stansen, Manuel Quaresma, Vincent Cottin, Stéphane Jouneau, Bruno Crestani, Ronan Thibault, Mathieu Lederlin, Laurent Vernhet, Claudia Valenzuela, Marlies Wijsenbeek, Michael Kreuter, Wibke Stansen, Manuel Quaresma, Vincent Cottin

Abstract

Background: Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF.

Methods: Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression.

Results: In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (- 283.3 [SE 22.4], - 207.9 [20.9] and - 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (- 312.7 [SE 32.2] versus - 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups.

Conclusions: In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not.

Trial registration: ClinicalTrials.gov ; Nos. NCT01335464 and NCT01335477 ; URL: www.clinicaltrials.gov .

Keywords: Interstitial lung diseases; Treatment; Vital capacity.

Conflict of interest statement

SJ reports personal fees from Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Galecto, Gilead, GlaxoSmithKline, LVL, Mundipharma, Novartis, Pfizer, Roche, and Savara-Serendex. BC reports grants and personal fees from Boehringer Ingelheim and Roche; grants from Apellis and MedImmune; and personal fees from AstraZeneca and Sanofi. RT has received fees or congress invitations from Aguettant, AstraZeneca, Baxter, Braun, Fresenius-Kabi, Lactalis, Nestlé, Nutricia, Roche, Sanofi, Servier, and Shire. ML reports personal fees from AstraZeneca, Boehringer Ingelheim, Fresenius-Kabi, Roche, and Siemens Healthineers. LV reports grants from Boehringer Ingelheim. CV reports personal fees from Boehringer Ingelheim, Hoffmann-La Roche, and Galapagos. MW reports grants and fees paid to her institution from Boehringer Ingelheim and Hoffmann-La Roche; fees paid to her institution from Galapagos and Respivant. MK reports grants and personal fees from Boehringer Ingelheim and Roche. WS and MQ are employees of Boehringer Ingelheim. VC reports research grants, personal fees, and non-financial support from Boehringer Ingelheim; personal fees from AstraZeneca, Bayer/Merck Sharp & Dohme, Celgene, Fibrogen, Galapagos, Galecto, Novartis, Sanofi, and Shionogi; and personal fees and non-financial support from Actelion, and Roche/Promedior.

Figures

Fig. 1
Fig. 1
Annual rate of decline in FVC (mL/year) assessed over 52 weeks by BMI at baseline
Fig. 2
Fig. 2
Change from baseline in FVC (mL) over 52 weeks by BMI at baseline
Fig. 3
Fig. 3
Annual rate of decline in FVC (mL/year) over 52 weeks by weight loss over 52 weeks
Fig. 4
Fig. 4
Change from baseline in FVC (mL) over 52 weeks by weight loss over 52 weeks

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