High- and low-dose oral delayed-release mesalamine in children with mild-to-moderately active ulcerative colitis

Abstract

Objective: The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis.

Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity.

Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups.

Conclusions: Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.

Trial registration: ClinicalTrials.gov NCT00713310.

Conflict of interest statement

H.S.W.: consultant for Janssen Pharmaceuticals, Prometheus Laboratories, Mead Johnson, Salix, Shire, and AstraZeneca; grant support from Janssen Pharmaceuticals, Prometheus Laboratories, UCB Pharmaceuticals, Autism Research Institute, Pediatric IBD Foundation, and Nutricia. P.K.: employee of Procter&Gamble Pharmaceuticals and Warner Chilcott at the time of the study. M.B.H.: grant support from Shire, Salix Pharmaceuticals, Procter&Gamble Pharmaceuticals, UCB Pharmaceuticals, Janssen Pharmaceuticals, CCFA, and NIH (DK060617). M.K.: scientific board member of Mead Johnson Nutrition research grant “ALERNI Education Programme.” S.K.: sponsored research for Chr. Hansen; lectures provided for Abbott, Arla Foods, BioGaia, JGL, Nestlé, Nutricia, and MSD; grant support from FALK, Abbott, BioGaia, and Nestlé. J.A.Q.: consultant for Sigma-Tau, Prometheus Laboratories, and Santarus. B.Y.: employee of Procter&Gamble Pharmaceuticals at time of study; speakers bureau for Optimer, Santarus, and Forest; consultant to N-8, GlaxoSmithKline, Sucampo, and Procter&Gamble Pharmaceuticals; and grant funding (ISP) from Merck. The remaining authors report no conflicts of interest.