P602 Factors associated with discontinuation of initial and subsequent tumour necrosis factor inhibitors in a large paediatric inflammatory bowel disease observational cohort

Abstract

Objectives and Study: Tumour necrosis factor inhibitors (TNFi) are effective in treating children with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). However, nonresponse or loss of response to therapy may lead to sequential biologic treatment. Factors associated with TNFi discontinuation in children are not well known. The aim of this study was to assess for clinical factors associated with first and subsequent TNFi discontinuation in a large paediatric inflammatory bowel disease (IBD) cohort. Method(s): We performed a retrospective study using data from ImproveCareNow (ICN), a multicenter, prospective paediatric IBD registry. Patients with CD and UC who were treated with their first TNFi following enrolment into ICN were identified at 39 participating ICN clinical sites. Clinical information was obtained from the ICN database and through chart review. The association of factors with TNFi discontinuation was assessed using Cox regression analysis. Result(s): 846 patients (678 CD, 168 UC) who fulfilled inclusion criteria were identified. Infliximab (IFX) was used first in 89% of CD patients while 11% received adalimumab (ADA) first. Mean age at IBD diagnosis was 11.7 +/- 3.4 years and mean age at TNFi initiation was 13.3 +/- 3 years. At the time of first TNFi initiation, 64% (333/523) of CD patients had ileocolonic disease, 28% (175/623) had perianal involvement, 86% (557/649) had a non-penetrating, non-stricturing phenotype, and the mean shortPCDAI score was 24.2 (Table 1). For the UC patients, 79% (109/139) had pancolonic disease and mean PUCAI score was 35. Approximately half of UC and CD patients received at least a single thiopurine or methotrexate dose within the six months following the first TNFi start (Table 1). On univariate analysis, discontinuation of the first TNFi in CD was associated with colonic only vs ileocolonic disease location (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.28-2.94, P = 0.0020, and with higher shortPCDAI (HR, 1.01 per 1 unit increase in shortPCDAI; 95% CI, 1.00-1.02, P = 0.032) and prednisone use (HR, 1.49; 95% CI, 1.07-2.08, P = 0.017) at the time of TNFi initiation. Receipt of at least one dose of an immunomodulator in the 6 months following first TNFi initiation was not associated with TNFi discontinuation (P = 0.23). Discontinuation of the second TNFi (86% ADA, 14% IFX) in CD was associated with abnormal C-reactive protein (HR 3.33; 95% CI, 1.05-10.55, P = 0.041), lower albumin (P = 0.006) and hematocrit (P = 0.032) at the time of 2nd biologic initiation, and the presence of upper gastrointestinal (GI) tract CD (HR, 3.25; 95% CI, 1.13-9.35, P = 0.029). IFX was used first in 94% of UC patients, while 6% received ADA first. Discontinuation of the first TNFi in UC was more common with ADA compared to IFX (HR, 2.43; 95% CI, 1.02-5.80, P = 0.045). Conclusion(s): Multiple factors associated with TNFi discontinuation in paediatric IBD patients were identified, including colonic only and upper GI tract CD location as well as markers of more severe CD at TNFi initiation like prednisone use and higher shortPCDAI. Prospective studies are needed to confirm these findings (Table presented).