title: 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).
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®is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.
  
  
  OBJECTIVE
  To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm®, 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®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®; 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®(noninferiority for LAS41008 vs. Fumaderm®: 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®. 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.
authors: Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Schittenhelmstraße 7, 24105, Kiel, Germany.
authors: U
authors: U
authors: Mrowietz
authors: Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland.
authors: J C
authors: JC
authors: Szepietowski
authors: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors: R
authors: R
authors: Loewe
authors: Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors: P
authors: P
authors: van de Kerkhof
authors: Almirall S.A., Barcelona, Spain.
authors: R
authors: R
authors: Lamarca
authors: Almirall Hermal, Reinbek, Germany.
authors: W G
authors: WG
authors: Ocker
authors: Almirall Hermal, Reinbek, Germany.
authors: V M
authors: VM
authors: Tebbs
authors: Almirall S.A., Barcelona, Spain.
authors: I
authors: I
authors: Pau-Charles
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069462:Dimethyl Fumarate / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D000069462:Dimethyl Fumarate