title: Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis.
abstract: BACKGROUND
  Increased activity of intestinal alkaline phosphatase (AP) occurs locally in patients with ulcerative colitis (UC), aimed at repairing inflammatory tissue damage. We evaluated the safety and preliminary efficacy of exogenous AP administered to patients with UC in an open-label, first-in-patient exploratory trial, conducted in the Internal Medicine and Gastroenterology hospital departments in the Czech Republic and Italy.
  
  
  METHODS
  Twenty-one patients were enrolled (13 females), age 23-54 years, with steroid- and/or immunosuppressant-refractory, moderate/severe UC (Mayo score 6-11). Oral AP enzyme 30,000 U was administered daily for 7 days, intraduodenally. Efficacy outcomes were changes in Mayo score at Day 21 posttreatment; changes in Modified Truelove-Witts Severity index (MTWSI) at Days 21, 63; C-reactive protein and stool calprotectin levels at Days 7, 21, 63. Safety evaluations were adverse events and laboratory abnormalities reported up to Day 63 posttreatment.
  
  
  RESULTS
  No clinically relevant adverse events causing withdrawal or considered serious, or laboratory abnormalities or antibody formation against AP were observed. Mayo scores were significantly decreased at Day 21, and MTWSI at Days 21 and 63. C-reactive protein and stool calprotectin levels were decreased at Days 21 and 63. Clinical response on the Mayo score after a single 7-day AP course was 48% at Day 21.
  
  
  CONCLUSIONS
  In this uncontrolled trial, administration of exogenous AP enzyme daily over a 7-day course to patients with UC was associated with short-term improvement in disease activity scores, with clinical effects being observed within 21 days and associated with reductions in C-reactive protein and stool calprotectin. AP enzyme treatment was well tolerated and nonimmunogenic.
authors.affiliation: Centre for Gastroenterology, University Hospital, Prague, Czech Republic. milan.lukas@email.cz
authors.forename: Milan
authors.initials: M
authors.lastname: Lukas
authors.forename: Pavel
authors.initials: P
authors.lastname: Drastich
authors.forename: Michal
authors.initials: M
authors.lastname: Konecny
authors.forename: Paolo
authors.initials: P
authors.lastname: Gionchetti
authors.forename: Ondrej
authors.initials: O
authors.lastname: Urban
authors.forename: Franco
authors.initials: F
authors.lastname: Cantoni
authors.forename: Martin
authors.initials: M
authors.lastname: Bortlik
authors.forename: Dana
authors.initials: D
authors.lastname: Duricova
authors.forename: Michael
authors.initials: M
authors.lastname: Bulitta
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000008:administration & dosage* / Q000009:adverse effects; D002097:C-Reactive Protein / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology; D005243:Feces; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; D000469:Alkaline Phosphatase