Increasing dosages of mesalamine by 2.4 g/d for patients with quiescent ulcerative colitis can dramatically reduce concentrations of fecal calprotectin and ultimately decrease the likelihood of relapse, according to the results of a new Dose Escalation and Remission (DEAR) study published in the November issue of Clinical Gastroenterology and Hepatology (2014;12:1887-93.e3).
In an open-label, randomized controlled trial, 119 patients with quiescent ulcerative colitis (UC) in remission were screened for Simple Clinical Colitis Activity Index scores, fecal calprotectin (FC) of 50 mcg/gram, and intake of no more than 3 g of mesalamine per day between October 2008 and March 2012. These subjects were divided into four groups based on FC levels, with Group 1 comprising 58 representing a baseline of FC < 50 mcg/gram, and groups 2-4 having 61 individuals with elevated baseline FC levels. Group 1 patients were retained for an observational follow-up study but were not included in the randomized controlled trial.
Participants were either told to maintain their current medication regimen or were prescribed a multimatrix mesalamine of either 2.4 or 4.8 g/d for 6 weeks, depending on their initial FC levels, after which point FC levels were taken. Participants in Group 2 with FC < 50 mcg/g were kept in an observational follow-up study group, while the rest of the participants were randomly assigned to continue their 2.4 g/d regimen, or increase their intake to 4.8 g/d.
Individuals in Group 3 with FC levels greater than 50 mcg/g were randomly assigned to either the 2.4- or 4.8-g/d regimen for 6 weeks; after that point, those whose FC levels had decreased below 50 continued with their regimen while those whose FC levels remained high were upped to 4.8 g/d. Subjects in Group 4 who were not already on a multimatrix mesalamine regimen and whose FC levels were above 50 mcg/g were randomized to continue their medication or add 2.4 g/d of mesalamine; after 6 weeks, if FC levels remained above 50, the dosage was increased to 4.8 g/d.
The primary outcome of continued remission with FC no greater than 50 mcg/g was observed in 3.8% of controls and 26.9% of participants in the dose escalation group (P = .0496). Others within the same group experienced secondary outcomes of FC levels below 100 mcg/gram (P = .04) and below 200 mcg/g (P = .005). Furthermore, among patients who were in remission during the randomization phase of the study, relapse occurred far sooner in those whose FC was above 200 mcg/g than those whose FC levels were below that mark.
“Our study adds to the evidence supporting FC concentration as a valid biomarker for UC,” said lead authors Dr. Mark T. Osterman and Dr. Faten N. Aberra of the University of Pennsylvania’s department of medicine, Philadelphia. “Perhaps more importantly, our results offer a novel way to use FC testing to positively impact outcomes in UC. We demonstrated efficacy of intervention to reduce FC (a surrogate for mucosal inflammation) before symptoms develop in patients at potentially increased risk of relapse.”
Dr. Osterman is a consultant for AbbVie, Elan, Janssen, and UCB and receives research funding from UCB. Dr. Aberra is a consultant for Janssen and research investigator for Amgen, Janssen, and UCB. Other coauthors disclosed ties to numerous pharmaceutical companies.