P103 Impact of premedication and other variables on the formation of antibodies to infliximab in pediatric inflammatory bowel disease

Abstract

BACKGROUND: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor α approved for induction and maintenance of remission in inflammatory bowel disease (IBD). Loss of response to infliximab is a clinical challenge and has been associated with drug immunogenicity and formation of antibodies to infliximab (ATI). The role of premedication with corticosteroids in preventing ATI formation is controversial and poorly studied in children. The aim of this cross sectional study is to investigate the effect of corticosteroid premedication on the prevalence of ATI, as well as to identify other variables that may affect ATI formation and infliximab level. METHODS: The study cohort included pediatric IBD patients treated with infliximab at our institution and had first ATI testing between 1/1/2003 and 6/30/2018. Clinical data obtained included routine premedication, duration of infliximab therapy, infliximab level, age, sex, BMI percentile, albumin, CRP, fecal calprotectin, occurrence of an infusion reaction (IR), and concomitant use of immunomodulator at the time of testing. The above variables were compared between the premedicated and non-premedicated groups, ATI positive and negative groups, and detectable and undetectable infliximab level groups and analyzed with descriptive statistics. Continuous variables were assessed by t-test and categorical variables by chi-square contingency analysis. P value <0.05 indicates statistical significance. This study was approved by the Institutional Review Board. RESULTS: We identified a total of 289 patients, 171 males and 118 females with mean age of 14.6 ± 3.2 years. Reasons for ATI testing were therapeutic drug monitoring (59%), flare (33%), abnormal labs (7%), or IR (1%). The overall prevalence of detectable ATI was 35% (101/289). When we compared the premedicated group (n = 213) to the nonpremedicated group (n = 76), we found no significant difference in ATI prevalence (38% vs 28%, P = 0.113). The premedicated group had significantly longer infliximab therapy duration prior to the first ATI testing (491 ± 605 vs 161 ± 247 days, P < 0.001), and higher BMI percentile (60.5 ± 29.8 vs 48.3 ± 30.6, P = 0.002). No significant differences were found in other variables. Next, we observed that patients with detectable ATI were on infliximab therapy longer (550 ± 634 days vs 321 ± 487 days, P ≤ 0.001) and were less likely to be treated with concomitant immunomodulators (11% vs 23%, P = 0.011) compared to the undetectable ATI group. None of the other variables were significantly different. In addition, we found that detectable infliximab correlated significantly with normal CRP and albumin (P = 0.004 and P ≤ 0.001). Patients with undetectable infliximab were more likely to have an IR (10.4%) than patients with detectable infliximab (1.3%) (P < 0.001). Interestingly, concomitant immunomodulator use did not influence the likelihood of having detectable infliximab (19% vs 19%, P = 0.983). CONCLUSION(S): Our data suggests that premedication does not appear to decrease the prevalence of ATI formation. Our study confirms that concomitant immunomodulator therapy does lead to less ATI formation; however, immunomodulator therapy did not correlate with detectable infliximab. Detectable infliximab was the only variable that correlated with improved clinical parameters (CRP and albumin). Having undetectable infliximab, but not the lack of premedication or presence of ATI, increased the likelihood of IR.