Interstitial lung disease · Antifibrotics beyond IPF
Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease
| Design | Randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Nintedanib 150 mg orally twice daily |
| Control | Placebo |
| Population | 576 patients with systemic sclerosis-associated ILD, 51.9% diffuse cutaneous, 48.4% on mycophenolate at baseline |
| Inclusion criteria | First non-Raynaud's symptom within the past 7 years and HRCT fibrosis affecting at least 10% of the lungs. |
| Follow-up | 52 weeks |
| Primary endpoint | Annual rate of decline in FVC |
| Result | FVC decline -52.4 mL/year with nintedanib versus -93.3 mL/year with placebo (difference 41.0 mL/year, 95% CI 2.9 to 79.0, p=0.04). Sensitivity analyses using multiple imputation gave p values of 0.06 to 0.10. Modified Rodnan skin score and SGRQ did not differ. Gastrointestinal adverse events were more common with nintedanib. |
| Secondary endpoints | Modified Rodnan skin score, St George's Respiratory Questionnaire |
Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis.
The trial authors, in the published abstract
A positive trial that deserves its caveats stated plainly: p=0.04 on the primary analysis, but 0.06 to 0.10 when missing data are imputed, and nothing outside the lung improved. It supports adding nintedanib to mycophenolate rather than choosing between them.
Distler O, Highland KB, Gahlemann M, et al. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med 2019 Jun 27;380(26):2518-2528.