- Background: There are no prospective trials of mesalamine enemas in children with active Ulcerative Colitis (UC). Unlike in adults, most children with UC are not treated with enemas during the first year of disease. The goal of the current study was to prospectively evaluate the ability of mesalamine enemas to induce remission in children with mild to moderate UC failing to achieve remission with high dose oral mesalamine. Methods: This was a 3- week open label arm of a multicenter, single blinded randomized controlled trial for active UC (i.e. the MUPPIT trial). Children, aged 4–18 years of age, with a PUCAI score between 10–55 were enrolled after failing at least 3 weeks of full dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa enemas 25 mg/kg (max one gram) daily for three weeks in combination with the previous high dose oral mesalamine. The primary endpoint was clinical remission by week 3, defined as PUCAI<10; secondary endpoint was change in PUCAI of 20 points (i.e. response) or remission. Results: Thirty eight children were enrolled (mean age 14.6±2.3 years; 17/38 (45%) with extensive colitis. Clinical remission was obtained in 42% (n=16) while response rate was 71% (n=27) at week 3. Remission rates were similar between left sided (43%) and extensive (41%) colitis, and did not differ between mild (44%) or moderate (41%) disease (p>0.05 for both). Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission. Conclusions: Clinical remission can be markedly increased in children who are refractory to high dose oral mesalamaine by adding mesalamine enemas for 3 weeks, prior to commencing steroids.