title: Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.
abstract: OBJECTIVE
  Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC.
  
  
  METHODS
  We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 μg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 μg/g. Secondary outcomes were continued remission with FC <100 μg/g or <200 μg/g (among patients with pre-randomization values above these levels).
  
  
  RESULTS
  The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 μg/g (P = .04) and 200 μg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 μg/g compared with those with FC <200 μg/g (P = .01).
  
  
  CONCLUSIONS
  Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145.
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Osterman
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Faten N
authors.initials: FN
authors.lastname: Aberra
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Raymond
authors.initials: R
authors.lastname: Cross
authors.affiliation: South Jersey Gastroenterology, Marlton, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Liakos
authors.affiliation: Minnesota Gastroenterology, Bloomington, Minnesota.
authors.forename: Robert
authors.initials: R
authors.lastname: McCabe
authors.affiliation: Shafran Gastroenterology Center, Winter Park, Florida.
authors.forename: Ira
authors.initials: I
authors.lastname: Shafran
authors.affiliation: Atlanta Gastroenterology Associates, Atlanta, Georgia.
authors.forename: Douglas
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Chevy Chase Clinic Research and George Washington University Medical School, Washington, District of Columbia.
authors.forename: Robert
authors.initials: R
authors.lastname: Hardi
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Colleen
authors.initials: C
authors.lastname: Brensinger
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Erin
authors.initials: E
authors.lastname: Gilroy
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: lewisjd@mail.med.upenn.edu.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D005243:Feces / Q000737:chemistry*; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D039841:Leukocyte L1 Antigen Complex; D019804:Mesalamine
keywords: 5 Aminosalicylate; 5-ASA; Biomarker; MMX; Natural History