Efficacy and safety of nintedanib in elderly patients with progressive fibrosing interstitial lung diseases (ILDs)* 

Rationale Elderly ILD patients are more likely to be frail and to have comorbidities that complicate their care. We investigated the efficacy and safety of nintedanib in elderly patients with progressive fibrosing (PF-) ILDs other than idiopathic pulmonary fibrosis (IPF) in the INBUILD trial ([Abb. 1]).

Abb. 1  Rate of decline in FVC (m/year) over 52 weeks in the INBUILD trial in subgroups by age at baseline.

Methods Patients had a chronic fibrosing ILD other than IPF, reticular abnormality with traction bronchiectasis (with/without honeycombing) of>10% on HRCT, and met criteria for ILD progression within the 24 months before screening, despite management deemed appropriate in clinical practice. Patients were randomized to nintedanib or placebo. We analyzed the rate of decline in FVC (mL/year) over 52 weeks in subgroups by age<75 vs≥75 years at baseline. Interaction p-values were calculated to assess potential heterogeneity in the effect of nintedanib versus placebo between subgroups. Adverse events (AEs) are presented descriptively.

Results Of 663 patients, 126 (19.0%) were aged≥75 years at baseline. In patients aged<75 years and≥75 years, respectively, 52.0% and 61.1% were male, mean (SD) age was 62.8 (8.3) and 78.5 (3.1) years, weight 78.0 (17.5) and 72.4 (16.5) kg, BMI 28.5 (5.5) and 27.1 (4.3) kg/m², FVC 68.3 (15.3) and 71.9 (16.8)% predicted and DLco 46.5 (14.0) and 44.7 (12.1)% predicted. In placebo, the rate of decline in FVC was numerically greater in patients aged≥75 than<75 years (Figure). Nintedanib reduced the rate of decline in FVC in both subgroups by age, with a greater effect in patients aged≥75 than<75 years (p=0.03 for treatment-by-time-by-subgroup interaction). In the nintedanib and placebo groups, respectively, the proportions of patients with AEs leading to treatment discontinuation were 18.9% and 13.4% in patients aged<75 years and 36.8% and 18.8% in those aged≥75 years, and the proportions of patients with serious AEs were 42.9% and 45.8% in those aged<75 years and 50.9% and 63.8% in those aged≥75 years.

Conclusions In patients with PF-ILDs other the IPF, nintedanib reduced the rate of decline in FVC both in patients aged≥75 years and in younger patients, with a greater treatment effect in the elderly patients. AEs leading to treatment discontinuation were more frequent in patients aged≥75 than<75 years. Proactive management of AEs is important to help maintain patients on antifibrotic therapy.

Publication History

Article published online:
09 March 2023