Mesalamine Dose Escalation Reduces Fecal Calprotectin in Patients With Quiescent Ulcerative Colitis

Abstract

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. 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). 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). 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.