Abstract
Background: BIBF 1120 is an inhibitor of tyrosine kinase receptors involved in lung fibrosis progression.
Methods: The TOMORROW trial was a 12-month, placebo (PBO)-controlled study to investigate efficacy and safety of BIBF 1120 (50 mg, 100 mg, 200 mg, 300 mg per day) in IPF (∼85 pts per group). Annual rate of decline in forced vital capacity (FVC) was measured.
Results: FVC decline decreased from 0.17 L/year (50 mg) to -0.06 L/year (300 mg) vs 0.19 L/year in PBO (300 mg vs PBO: p=0.014; closed-testing multiplicity-corrected: p=0.064). Absolute changes from baseline in% pred FVC were -6.00, -4.58, -4.90, -3.15 and -1.04% in PBO and rising dose groups (200 mg: p=0.031; 300 mg: p=0.0002).
Absolute difference of% change in SpO2 was superior vs PBO by 0.44, 0.33, 1.36 and 1.12% for rising doses (200 mg: p=0.005; 300 mg: p=0.021). Incidence of acute exacerbations fell with dose (15.67, 13.03, 12.46, 7.46 and 2.44 per 100 patient years for PBO and rising doses). Gastrointestinal adverse events (AEs) increased with dose (31.8%, 38.4%, 36.0%, 57.0% and 74.1% in PBO and rising doses). AEs leading to discontinuation occurred in 25.9%, 23.3%, 16.3%, 14.0% and 30.6% of pts in PBO and rising dose groups. Fatal AEs (on-treatment) fell with dose (12, 10, 4, 5 and 1 pts for PBO and rising doses).
Conclusion: Treatment of IPF with BIBF 1120 reduced decline in lung function and incidence of acute exacerbations in a dose-dependent way.
- © 2011 ERS