Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm® - and placebo-controlled trial (BRIDGE)

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 moderateto- 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 >= 75% 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 = 267, LAS41008; n = 273, Fumaderm (R); n = 131, placebo). At week 16, 37.5% of patients treated with LAS41008 achieved PASI 75, compared with 15.3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0.001) and 40.3% receiving Fumaderm (R) (noninferiority for LAS41008 vs. Fumaderm (R) : P < 0.001). Overall, 33% of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13.0% receiving placebo (P < 0.0001; LAS41008 superiority vs. placebo) and 37.4% 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 moderateto- severe chronic plaque psoriasis.