Review of the Impact of Weight Loss and Body Mass Index in Clinical Trials of Nintedanib in Interstitial Lung Disease.

INTRODUCTION: Weight loss and malnutrition are poor prognostic factors in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). In this review, the effect of weight loss and body mass index (BMI) on the decline in forced vital capacity (FVC) was assessed using published secondary analyses of the placebo arms of clinical trials of nintedanib in IPF and PPF, as well as previously unpublished analyses of the INPULSIS trials in IPF. METHODS: Published secondary analyses of placebo arms from clinical trials of nintedanib in IPF and PPF were reviewed. In addition, previously unpublished analyses of pooled INPULSIS trial data in IPF were conducted to evaluate the relationship between baseline BMI, weight loss, and FVC decline. RESULTS: In published analyses, both low BMI at baseline and weight loss during treatment were associated with greater decline in FVC. New analyses of INPULSIS data indicated that the effect of weight loss on FVC decline was most pronounced in patients with lower BMI (< 25 kg/m2) at baseline. In those with mid-range BMI (25 to < 30 kg/m2), patients with weight loss > 5% also had a greater decline in FVC than those who lost ≤ 5% body weight. An adverse effect of weight loss was not observed in patients with high baseline BMI (≥ 30 kg/m2). While gastrointestinal events and weight loss are recognised side effects for nintedanib, patients treated with nintedanib had lower FVC decline than those given placebo in all subgroups, regardless of weight loss or baseline BMI. CONCLUSION: Increased attention to nutrition and management of gastrointestinal side effects to help patients adhere to treatment can improve outcome of treatment for IPF and PPF. CLINICAL TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT02999178 (INBUILD), registered December 19, 2016. CLINICALTRIALS: gov identifiers: NCT01335464 and NCT01335477 (INPULSIS-1 and INPULSIS-2), both registered April 13, 2011.