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

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 mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of 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 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/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 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion 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: NCT00652145

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target

“…Fecal calprotectin has been shown to correlate well with mucosal healing ( 16,164,165 ) (CEBM 2b). While fecal calprotectin has only recently been used as an end point in randomized controlled trials, it has been shown to correlate with response to induction therapy and to be predictive of loss of response to maintenance therapy ( 86,(164)(165)(166)(167) …”

Clinicians’ Guide to the Use of Fecal Calprotectin to Identify and Monitor Disease Activity in Inflammatory Bowel Disease

“…A randomized trial involving patients with quiescent UC found that FC levels were lowered by increasing the dose of mesalamine (28). Moreover, relapse occurred sooner in patients with FC levels >200 µg/g compared with those with lower FC levels (P=0.01).…”

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study

“…This approach, with targeted medical therapy using calprotectin to identify patients with UC at impending risk of a flare, and to optimize treatment for those before symptoms appear, is new. In a very recent trial by Osterman et al 24 a similar concept was presented; however, we preferred to monitor our patients over time and to maintain the current 5-ASA agent, instead of changing regimen. We also excluded patients with previous anti-TNF therapy, to achieve a more uniform group of patients.…”