Anti-tumor necrosis factor alpha (anti-TNFa) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD) and carry risks for adverse events. We aimed to assess the relationship between anti-TNFa trough concentrations and adverse events rate among pediatric patients with IBD. The medical records of pediatric patients with IBD who were treated with anti-TNFa agents from 2015 to 2020 and had sequential monitoring of trough concentration (TC) were reviewed retrospectively for the presence of adverse events. The study cohort included 135 eligible patients (59 [43.7%] girls, mean age at diagnosis 12.9 [AE3] years, 111 [82.2%] Crohn disease) who had 1589 measurements of TCs (1037 [63%] infliximab). During a median follow-up period of 1.7 years (IQR 1.1-2.7), we recorded 156 adverse events in 50 patients (37%). Higher TCs were not associated with higher rate of anti-TNFarelated adverse events whereas these events (excluding increase in liver transaminases) were associated with younger age.

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Objectives: In patients with inflammatory bowel diseases (IBD), data on trough concentration (TC) response to adjustments of anti-tumor necrosis factor (TNFα) are scarce. Methods: We included pediatric patients with IBD who were treated with anti-TNFα agents and had sequential monitoring of TC pre- and post-adjustment. Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded. Results: For the entire cohort (86 patients), median age at diagnosis was 13.2 (interquartile range, 10.7–14.9) years [females, 48%; Crohn disease (CD), 72%]. For infliximab, 58 patients had 201 interval changes and 26 had dose increase. Increase in TC following dose increase could not be predicted due to significant variability (P = 0.9). For every 10% decrease in interval, TC was increased by 1.6 µg/mL or by 57.2% (P = 0.014). Perianal disease was associated with attenuated response. For every 10% increase in interval, TC was decreased by 0.66 µg/mL or by 4.2%. The diagnosis of CD was associated with reduced response to interval increase. For adalimumab, 28 patients had 31 and 12 events of interval decrease or increase, respectively. Interval decrease resulted in increased median TC from 4.5 (3.5–5.3) µg/mL to 8.1 (6.5–10.5) µg/mL (X1.8) while interval increase resulted in TC change from 15.5 (12.8–18.6) µg/mL to 9.7 (6.5–14.6) µg/mL (:1.6) (P < 0.001 for both). Increase in delta TC was associated with younger age, and with absence of perianal disease (P = 0.001). Conclusion: Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab while response to infliximab adjustment are more variable.

Background Anti-tumor necrosis factor alpha (anti-TNFα) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD). Prolonged use of anti-TNFα therapy has been linked to a number of adverse events. We aimed to assess the relationship between serum trough concentrations (TC) of anti-TNFα and adverse events rate among patients with pediatric IBD. Methods The medical records of 135 pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of TC were reviewed retrospectively for the presence of adverse events (infusion reactions, infections, acute cutaneous reactions, psoriatiform rashes, elevated transaminases and others). The association between demographic or disease related variables and adverse events were analyzed using multivariate analysis. Results Out of 135 patients, [59 (43.7%) female, mean age at diagnosis 12.9 (±3)years, 111 (82.2%) Crohn’s disease] who had 1645 measurements of TC [1037(63%) infliximab, range 0-46 µgr/ml] during a median follow-up period of 1.7 years (1.1-2.7), we recorded 120 adverse events in 42 patients (31%). When analyzing TC as continuous measure or as a categorical measure (&gt; or &lt;10 µgr/ml) there were not associated with a higher rate of adverse events (p=0.9).Patients who reported non-infusion related adverse events were younger at the time of diagnosis (mean age 11.4±3.9 vs.13.3±2.8years) than those without adverse effect (p=0.029). There was no statistically significant correlation between other variables (gender, disease type, Paris classification, extra-intestinal manifestation, perianal disease, and the pediatric disease activity index) and the occurrence of adverse events. Conclusion Based on our cohort, higher TCs were not associated with higher rate of anti-TNF related adverse events whereas younger age at diagnosis increased the risk for such events. The study protocol was approved by the local Internal Review Board at the Rabin/Schneider Medical Center (RMC0320-10).

Background Fecal calprotectin (FC) is a sensitive surrogate marker of mucosal inflammation in inflammatory bowel disease (IBD). Our aim was to asses the effect of anti-tumor necrosis factor alpha (TNFα) induction and maintenance therapy on FC levels in children with IBD. Methods The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 were reviewed retrospectively. We identified 63 patients who had FC levels measured prior to anti TNFα induction with sequential measurements during the first months of therapy. The main outcome measures were time to FC response according to cut-offs of 250,150,100 and 50µgr/gr. Variables affecting FC response were analyzed using multivariate analysis. Results Out of 63 patients, mean age 13.6 (±3) years, females 28(44.4%),54 (85.7%) had Crohn’s disease. The median (interquartile range) FC at baseline was 715 µgr/gr (312–1700). The outcomes of &lt;250, &lt;150, &lt;100 and &lt;50 µgr/gr were achieved by 52 (82%), 51 (81%), 44 (70%) and 32 (50%) patients, respectively. The mean time (± standard error) for achieving these cut-offs were 4.8 ±0.8, 7.9±1.3, 10±1.8 and 18.5±7.2 months, respectively. There was no statistically significant correlation between age, gender, type of disease, Paris classification, extra-intestinal manifestation, albumin levels, erythrocyte sedimentation rate, C-reactive protein and the pediatric disease activity indexes at baseline and FC response. Furthermore, there was no statistically significant correlation between anti TNFα trough concentration during induction and FC response. Conclusion In pediatric patients with IBD, FC response (&lt;250µgr/gr) was achieved by the majority of patients within a relatively short period of time. Nevertheless, calprotectin normalization (&lt;100µgr/gr) required an average period of approximately one year in responders.