Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis
Mark T Osterman, Faten N Aberra, Raymond Cross, Steven Liakos, Robert McCabe, Ira Shafran, Douglas Wolf, Robert Hardi, Lisa Nessel, Colleen Brensinger, Erin Gilroy, James D Lewis, DEAR Investigators, James D Lewis, Raymond Cross, Samir Shah, Douglas Wolf, Robert McCabe, Steven Liakos, Richard Chasen, Seth Persky, Seymour Katz, Ira Shafran, Raymond Phillips, Daniel Geenan, Alex Sherman, Robert Hardi, Mark T Osterman, Faten N Aberra, Raymond Cross, Steven Liakos, Robert McCabe, Ira Shafran, Douglas Wolf, Robert Hardi, Lisa Nessel, Colleen Brensinger, Erin Gilroy, James D Lewis, DEAR Investigators, James D Lewis, Raymond Cross, Samir Shah, Douglas Wolf, Robert McCabe, Steven Liakos, Richard Chasen, Seth Persky, Seymour Katz, Ira Shafran, Raymond Phillips, Daniel Geenan, Alex Sherman, Robert Hardi
Abstract
Background & aims: 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.
Keywords: 5 Aminosalicylate; 5-ASA; Biomarker; MMX; Natural History.
Conflict of interest statement
Potential conflicts of interest:
Dr. Osterman – Consultant for Abbvie, Elan, Janssen, UCB; Research funding from UCB.
Dr. Aberra – Consultant for Janssen, Research investigator for Amgen, Janssen, UCB.
Dr. Lewis – Consultant for Elan, Proctor & Gamble, GlaxoSmithKline, Allos Therapeutics, Millennium Pharmaceuticals, AbbVie, Prometheus, Lilly, Shire Pharmaceuticals, Nestle, Janssen, AstraZeneca, Amgen, Merck; Research funding from Centocor, Takeda, Bayer.
Dr. Shafran reports no potential conflicts of interest.
Ms. Nessel reports no potential conflicts of interest.
Dr. Hardi – Consultant for Abbvie, Takeda, Santarus
Dr. McCabe – AbbVie Speakers Bureau
Dr. Cross – Consultant for Abbvie and Janssen; Educational and Research Funding from Abbvie, Janssen, and UCB..
Dr. Wolf – Consultant for AbbVie, Centocor, Salix, Warner Chilcot, Research investigator for Genetech, Millennium Research Group, Pfizer, Receptos
Dr. Liakos reports no potential conflicts of interest.
Ms. Gilroy reports no potential conflicts of interest.
Ms. Brensinger reports no potential conflicts of interest.
Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Source: PubMed