Journal Article

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Bargagli, Elena, Glaspole, Ian, Bonella, Francesco, Caro, Fabian, Bendstrup, Elisabeth, Stansen, Wibke, Quaresma, Manuel, Glassberg, Marilyn K., Orsatti, Leticia

2021

Overview

Background Idiopathic pulmonary fibrosis (IPF) predominantly affects individuals aged > 60 years who have several comorbidities. Nintedanib is an approved treatment for IPF, which reduces the rate of decline in forced vital capacity (FVC). We assessed the efficacy and safety of nintedanib in patients with IPF who were elderly and who had multiple comorbidities. Methods Data were pooled from five clinical trials in which patients were randomised to receive nintedanib 150 mg twice daily or placebo. We assessed outcomes in subgroups by age < 75 versus ≥ 75 years, by < 5 and ≥ 5 comorbidities, and by Charlson Comorbidity Index (CCI) ≤ 3 and > 3 at baseline. Results The data set comprised 1690 patients. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks versus placebo in patients aged ≥ 75 years (difference: 105.3 [95% CI 39.3, 171.2]) (n = 326) and < 75 years (difference 125.2 [90.1, 160.4]) (n = 1364) (p = 0.60 for treatment-by-time-by-subgroup interaction), in patients with < 5 comorbidities (difference: 107.9 [95% CI 65.0, 150.9]) (n = 843) and ≥ 5 comorbidities (difference 139.3 [93.8, 184.8]) (n = 847) (p = 0.41 for treatment-by-time-by-subgroup interaction) and in patients with CCI score ≤ 3 (difference: 106.4 [95% CI 70.4, 142.4]) (n = 1330) and CCI score > 3 (difference: 129.5 [57.6, 201.4]) (n = 360) (p = 0.57 for treatment-by-time-by-subgroup interaction). The adverse event profile of nintedanib was generally similar across subgroups. The proportion of patients with adverse events leading to treatment discontinuation was greater in patients aged ≥ 75 years than < 75 years in both the nintedanib (26.4% versus 16.0%) and placebo (12.2% versus 10.8%) groups. Similarly the proportion of patients with adverse events leading to treatment discontinuation was greater in patients with ≥ 5 than < 5 comorbidities (nintedanib: 20.5% versus 15.7%; placebo: 12.1% versus 10.0%). Conclusions Our findings suggest that the effect of nintedanib on reducing the rate of FVC decline is consistent across subgroups based on age and comorbidity burden. Proactive management of adverse events is important to reduce the impact of adverse events and help patients remain on therapy. Trial registration: ClinicalTrials.gov NCT00514683, NCT01335464, NCT01335477, NCT02788474, NCT01979952.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Adult / Adverse events / Age / Age Factors / Aged / Aged patients / Aged, 80 and over / Clinical trials / Comorbid patients / Comorbidity / Diabetes / Diarrhea / Disease Progression / Drug therapy / Dyspnea / Female / Fibrosis / Gastroesophageal reflux / Humans / Hypertension / Idiopathic Pulmonary Fibrosis - diagnosis / Idiopathic Pulmonary Fibrosis - drug therapy / Idiopathic Pulmonary Fibrosis - epidemiology / Idiopathic Pulmonary Fibrosis - physiopathology / Indoles - adverse effects / Indoles - therapeutic use / Liver diseases / Lung - drug effects / Lung - physiopathology / Lung diseases / Male / Medicine / Medicine & Public Health / Middle Aged / Mortality / Older people / Patients / Placebos / Pneumology/Respiratory System / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Pulmonary Diffusing Capacity / Pulmonary fibrosis / Quality of life / Questionnaires / Randomized Controlled Trials as Topic / Safety / Subgroups / Time Factors / Treatment Outcome / Vital Capacity