Intensified infliximab induction is associated with improved response and decreased colectomy in steroid-refractory paediatric ulcerative colitis.

Abstract

Background\nInfliximab pharmacokinetics in steroid-refractory ulcerative colitis (UC) suggest a need for higher dosing, but data concerning efficacy of intensification in this setting are lacking in children and inconsistent overall.\n\n\nMethods\nPaediatric patients (N=125) treated with infliximab for steroid-refractory or steroid-dependent UC were retrospectively reviewed. Outcomes (clinical response and remission, colectomy, mucosal healing, safety) with standard vs. intensified induction (mean induction dose ≥7mg/kg or interval ≤5 weeks between doses 1 and 3) were compared.\n\n\nResults\nAmong 125 patients (median age 14 years; median UC duration 0.7 years, 74 steroid-refractory), 73 (58%) received standard induction and 52 (42%) received intensified induction. Overall, 73 (58%) achieved remission (judged by PGA and PUCAI≤10). Among remitters, 7(10%) experienced secondary loss of response by median 0.7 (IQR 0.4-1.0) years. 17/74 (23%) steroid-refractory patients and 12/51 (24%) steroid-dependent patients underwent colectomy. Intensified induction in steroid-refractory patients was associated with a higher chance of remission (HR 3.2, p=0.02) and lower chance of colectomy (HR 0.4, p=0.05) but did not improve outcomes in steroid-dependent patients. During follow-up, 46/73 (63%) remitters had regimen individualization, with similar rates of return to standard dosing after 1 year between those with initial intensified or standard induction. Follow-up endoscopy, performed in 35/73 remitters, demonstrated mucosal healing for 66%. Adverse events were rare, despite use of intensified regimens.\n\n\nConclusions\nThese data suggest a benefit to intensified infliximab induction specifically among children with steroid refractory UC. Prospective studies comparing dosing regimens and incorporating therapeutic drug monitoring should be undertaken.