Outcomes of a National Cohort of Children with Acute Severe Ulcerative Colitis.

AIM: All Irish children with ulcerative colitis (UC) attend the National Centre for Paediatric Gastroenterology at Our Lady's Children's Hospital, Crumlin. The aim of this study was to determine the outcomes of children with acute severe ulcerative colitis (ASC) and the impact of infliximab on these outcomes following its introduction for this indication in 2011. METHODS: A retrospective chart review of all patients admitted with ASC between January 1, 2009 and December 31, 2015 was undertaken. Patients were identified from the departmental database cross-referenced with the hospital inpatient enquiry system. Inpatients with a paediatric ulcerative colitis activity index (PUCAI) of ≥65 were included. Data collected included baseline demographic and laboratory data, concomitant treatments, PUCAI scores on days 3 and 5, second-line treatments, surgery, and discharge outcomes. Infliximab dose, frequency, and available therapeutic drug monitoring results were recorded, along with clinical response outcomes (remission, primary, and secondary loss of response). The cohort was sub-analysed to determine if there was any era effect pre- and post-introduction of infliximab (2009-2010 and 2011-2015, respectively). RESULTS: Fifty-five patients (M:F = 1.4:1) were treated for acute severe colitis over the study period (8 in the pre-infliximab and 47 in the post-infliximab era) and 46/55 (86%) had steroid-refractory disease. Of these, 7/8 (88%) required colectomy in the pre-infliximab era, compared with 15/47 (36%) in the post-infliximab era. The remission rate with second-line infliximab was 61% at maximal follow-up. There were no identifiable factors that predicted likely success or failure of infliximab, including gender, CRP, day-3 and day-5 PUCAI scores. Of the 33 patients treated with infliximab, dose increase was required in 23/33 (70%); 21/33 (64%) received an accelerated dose schedule, and 9/33 (27%) eventually needed colectomy. Primary and secondary loss of response to infliximab was seen in one and nine patients, respectively. CONCLUSION: This is the first population-based study of the outcomes of severe UC in Irish children, and suggests a higher burden of steroid-refractory disease compared with previous international studies. While infliximab treatment has led to reduction in colectomy rates, a significant proportion of patients lose therapeutic effect.

Golimumab: early experience and medium-term outcomes from two UK tertiary IBD centres.

OBJECTIVE: To gain an understanding of the effectiveness of golimumab in a 'real-world' setting. DESIGN: Retrospective cohort study using prospectively maintained clinical records. SETTING: Two UK tertiary IBD centres. PATIENTS: Patients with ulcerative colitis (UC) were given golimumab at Guy's & St Thomas and King's College Hospitals between September 2014 and December 2016. INTERVENTION: Golimumab, a subcutaneously administered antitumour necrosis factor agent. MAIN OUTCOME MEASURES: Clinical disease activity was assessed at baseline and at the first clinical review following induction therapy using the Simple Clinical Colitis Activity Index (SCCAI). Response was defined as an SCCAI reduction of 3 points or more. Remission was defined as an SCCAI of less than 3. RESULTS: Fifty-seven patients with UC completed golimumab induction therapy. Paired preinduction and postinduction SCCAI values were available for 31 patients and fell significantly from 7 (2-19) to 3 (0-11) (p<0.001). To these 31, an additional 13 patients who did not have paired SCCAI data but stopped treatment due to documented 'non-response' in the opinion of their supervising clinician, were added. Among this combined cohort, 23/44 (52%) had a clinical response, 15/44 (34%) achieved remission and 13/44 (30%) achieved corticosteroid-free remission.Faecal calprotectin and CRP fell (FC: pre-induction: 1096 (15-4800) µg/g, post-induction: 114 (11-4800) µg/g, p = 0.011; n = 20; CRP: pre-induction: 4 (1-59) mg/L, post-induction: 2 (1-34) mg/L, p = 0.01 for n = 43). Post-induction endoscopy was carried out in 23 patients and a mucosal healing (Mayo 0 or 1) rate of 35% was observed. CONCLUSIONS: Our experience mirrors previously reported real-world cohorts and demonstrates similar outcomes to those observed in randomised controlled trials. These data demonstrate a meaningful reduction in clinical, biochemical and endoscopic disease activity as well as a steroid-sparing effect in patients with previously refractory disease.