An audit of acute severe colitis outcomes in children in the modern era of accelerated infliximab

Abstract

Background and Aim: Acute severe ulcerative colitis (ASUC) is a catastrophic presentation of ulcerative colitis with significant short- and long-term morbidities, including risk of colectomy. Recent pediatric practice is to be more aggressive with biological agents, using accelerated dosing. We report our tertiary statewide service's experience of children presenting with ASUC over the past 8 years, focusing on outcomes and indicators. Methods: We performed a retrospective chart review of pediatric patients presenting with ASUC (Pediatric Ulcerative Colitis Activity Index [PUCAI] >65) to the Queensland Children's Hospital from January 2014 to April 2021. Indicators of severity were reviewed, including response to treatment based on PUCAI score (Days 0, 3, 5, and 7), infliximab (IFX) dosing schedule, body mass index (BMI), sex, C-reactive protein (CRP) level, and albumin level. Results: In 8 years, 52 children presented with 67 episodes of ASUC (median age, 11.4 years; 0.7-16; 23 [44%] male; and average BMI, 19.2 kg/m2 [normal, 18-25 kg/m2]). By Day 7, nine children responded to intravenous steroids and did not require second-line therapy. Of these nine children, one child had ASUC recurrence that again responded to steroids 2 years later, none escalated to acute IFX, none came to colectomy during follow-up (1 to 4 years), six had steroid-free remission at 12 months, and two started adalimumab for chronic colitis in the first year. Of the 52 children, 33 required IFX as second-line therapy, at a median of Day 5. PUCAI scores on Day 7 had improved to <40 in 25/33 children. Two children did not respond to second-line IFX. In the following 12 months, seven children required maintenance IFX to be restarted for ongoing disease or steroid dependence. Fifteen children (M = F) had a further ASUC episode. Those who developed a second episode of ASUC had a higher Day 7 PUCAI during the first presentation (mean, 27.2 vs 15.5), higher CRP level (32 vs 28 mg/L), and higher platelet count (468 vs 417 × 109/L), but there were no predictive cutoffs. Day 1 PUCAI, albumin level, and BMI showed no indicative value. Colectomy rates at 3, 6, and 12 months were 5/50 (10%), 7/49 (14%), and 10/42 (24%), respectively. Indicators for colectomy included CRP level (mean, 70 vs 20 mg/L) and PUCAI on Day 5 (46 vs 33) and Day 7 (35 vs 21). Fecal calprotectin level showed no indicative value (mean, 2267 vs 3049 μg/g). Children in steroid-free remission at 12 months had lower CRP levels (mean, 23 vs 34 mg/L) at presentation and lower PUCAI on Day 5 (31 vs 40) and Day 7 (21 vs 26). Accelerated IFX practice (vs 3 × 5 mg/kg at 0, 2, and 6) has been employed since 2014, with total dosing over the first 4 weeks of IFX therapy showing no difference when comparing the eras of 2014-2017 (20 mg/kg) and 2018-2021 (21 mg/kg). There were 33 children who received accelerated IFX: five with >30 mg/kg, 24 with >20-30 mg/kg, and four with >10- 20 mg/kg. In these children, rates of steroid-free clinical remission (PUCAI < 10) at 3, 6, and 12 months were 77% (23/30), 60% (18/30), and 60% (15/25), respectively. Cumulative colectomy rates at 3, 6, and 12 months for those receiving second-line IFX were 10% (3/30), 20% (6/ 30), and 28% (7/25), respectively. Indicators for colectomy were CRP level at presentation (63.5 vs 20 mg/L; 70% having colectomy had a CRP level >25 mg/L), male sex (7 vs 3), PUCAI at Day 5 (mean, 41.1 vs 33), and PUCAI at Day 7 (mean, 35 vs 21). Conclusion: In the modern era of accelerated IFX dosing for second-line therapy, colectomy remains a significant complication in children presenting with ASUC, and the implementation of higher IFX dosing is still accompanied by high colectomy rates. The best indicators of outcome were consistent with published literature: Day 5-7 clinical response/PUCAI and CRP level.L6361721932021-10-12 <br />