Abstract
BACKGROUND: Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm(R) is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient. OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm(R) , in adults with moderate-to-severe chronic plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm(R) or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving +AD4-/+AD0- 75+ACU- improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in the Physician's Global Assessment (PGA) at week 16. RESULTS: In total, 671 patients were randomized and included in the full analysis set (n +AD0- 267, LAS41008+ADs- n +AD0- 273, Fumaderm(R) +ADs- n +AD0- 131, placebo). At week 16, 37.5+ACU- of patients treated with LAS41008 achieved PASI 75, compared with 15.3+ACU- receiving placebo (superiority for LAS41008 vs. placebo: P +ADw- 0.001) and 40.3+ACU- receiving Fumaderm(R) (noninferiority for LAS41008 vs. Fumaderm(R) : P +ADw- 0.001). Overall, 33+ACU- of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13.0+ACU- receiving placebo (P +ADw- 0.0001+ADs- LAS41008 superiority vs. placebo) and 37.4+ACU- receiving Fumaderm(R) . Most treatment-related adverse events were classed as 'mild' in severity. CONCLUSIONS: LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.
