Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

Area of Science:

• Pulmonology
• Rheumatology
• Pharmacology

Background:

• Interstitial lung disease (ILD) is a significant complication and cause of mortality in systemic sclerosis.
• Nintedanib, a tyrosine kinase inhibitor, exhibits antifibrotic and anti-inflammatory properties in preclinical models relevant to systemic sclerosis and ILD.

Purpose of the Study:

• To evaluate the efficacy and safety of nintedanib in patients diagnosed with ILD associated with systemic sclerosis.
• To assess the impact of nintedanib on the rate of lung function decline and other systemic sclerosis manifestations.

Main Methods:

• A randomized, double-blind, placebo-controlled trial involving 576 patients with systemic sclerosis and ILD.
• Patients received either 150 mg of nintedanib orally twice daily or a placebo for 52 weeks.
• The primary endpoint was the annual rate of decline in forced vital capacity (FVC); secondary endpoints included changes in skin score and respiratory quality of life.

Main Results:

• Nintedanib demonstrated a statistically significant reduction in the annual rate of FVC decline compared to placebo (-52.4 ml/year vs. -93.3 ml/year, P=0.04).
• No significant differences were observed between groups in the modified Rodnan skin score or St. George's Respiratory Questionnaire total score.
• Diarrhea was the most frequent adverse event, occurring in 75.7% of patients in the nintedanib group versus 31.6% in the placebo group.

Conclusions:

• Nintedanib effectively slowed the annual rate of FVC decline in patients with ILD associated with systemic sclerosis.
• The drug did not show significant benefits for other systemic sclerosis symptoms, and gastrointestinal adverse events, particularly diarrhea, were more common.
• The safety profile was consistent with previous studies in idiopathic pulmonary fibrosis.