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Randomized Controlled Trial
. 2014 Nov;12(11):1887-93.e3.
doi: 10.1016/j.cgh.2014.03.035. Epub 2014 Apr 30.

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis

Mark T Osterman  1 , Faten N Aberra  1 , Raymond Cross  2 , Steven Liakos  3 , Robert McCabe  4 , Ira Shafran  5 , Douglas Wolf  6 , Robert Hardi  7 , Lisa Nessel  8 , Colleen Brensinger  8 , Erin Gilroy  8 , James D Lewis  9 ; DEAR Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis

Mark T Osterman et al. Clin Gastroenterol Hepatol. 2014 Nov.

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.

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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.

Figures

Figure 1
Figure 1
Follow-up of patients in the randomized trial and the observational cohort. FC – Fecal calprotectin concentration in mcg/g. Flare – clinical relapse. REM – In clinical remission. LTF – Lost to follow-up.
Figure 2
Figure 2
FC levels were decreased in the group randomized to dose escalation. Panel A includes all randomized patients; those without a post randomization FC level are categorized as not achieving the outcome. Panel B includes only patients with a FC level measured after randomization or who experienced documented clinical relapse.
See this image and copyright information in PMC

Comment in

References

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