Early Serum Infliximab Levels in Pediatric Ulcerative Colitis

Abstract

Background: Data on serum infliximab concentrations during induction in pediatric ulcerative colitis are limited. The study aim is to evaluate the relationship between serum infliximab concentrations during induction and short-term clinical remission in children with ulcerative colitis.Methods: We carried out a prospective, multi-center cohort study in pediatric patients with ulcerative colitis. Serum infliximab concentrations were collected at peak dose #1, week 1, trough pre-dose #2, and trough pre-dose #3. Infliximab dosing was left to investigator discretion. Clinical remission was defined by pediatric ulcerative colitis activity index <10 at week 8.Results: Twenty-four of thirty-four subjects (71%) achieved clinical remission at week 8. The median infliximab concentrations were 33.0 μg/mL (interquartile range: 26.5–52.1 μg/mL) pre-dose #2 and 22.5 μg/mL (interquartile range:15.9–32.3 μg/mL) pre-dose #3. Trough pre-dose #2 infliximab concentration yielded area under receiver operator characteristic curve 0.7, 95% CI: 0.5–0.9 in predicting week 8 clinical remission; a cut-off of 33.0 μg/mL yielded 62.5% sensitivity, 66.7% specificity. Trough pre-dose #3 infliximab concentrations were lower for subjects <10 years compared to ≥ 10 years [median 15.9 μg/mL, interquartile range (IQR) 8.5–21.8 μg/mL vs. 27.7 μg/mL, IQR 17.2–46.7 μg/mL, p = 0.01] and correlated with baseline weight (Spearman's rank correlation coefficient 0.45, p = 0.01). The median half-life following first IFX dose was 6.04 days (IQR 5.3–7.9 days).Conclusions: Infliximab concentrations ≥33 μg/mL prior to the second dose were associated with week 8 clinical remission. As young age and low body weight impact infliximab concentration, prospective studies with proactive adjustment in pediatric patients with ulcerative colitis should be carried out. Clinicians caring for children with UC should diligently adjust and monitor infliximab to optimize response.

Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model

“…It was previously demonstrated that a high proportion of anti-TNFα treated children with IBD will eventually undergo treatment escalation either by increasing dose or by decreasing the interval between infusions/injections (2,16). Furthermore, a clear association between higher TC and both clinical and mucosal response has been established for adalimumab and infliximab (3)(4)(5). In adalimumab treated patients, as was shown in previous studies (17,18), we found that interval change resulted in an almost linear response in adalimumab TC, whereas in infliximabtreated patients, the response to interval change was less predictable and the response to dose escalation could not have been predicted at all.…”

“…The influence of weight on the clearance of mAbs is not linear (20,29). A nonlinear correlation between body weight and infliximab clearance have been seen in several pediatric studies (5,16,29,30). In contrast to infliximab, adalimumab dose is constant and is not determined based on body weight, thus, the effect of age, body weight, and body surface area (BSA) on TC response could be assessed.…”

Cell division control 42 elevates during infliximab therapy, and its increment relates to treatment response in ulcerative colitis patients

“…4,7,8 However, approximately 20%-30% of UC patients experience poor treatment response to IFX and disease progression, which further impairs their long-term clinical outcomes. 9,10 Hence, it is obligatory to identify potential biomarkers to monitor disease progression and predict IFX efficacy in UC patients.…”

“…IFX, as one approved biologic regimen for UC management, shows a superior short‐term clinical response rate and long‐term mucosal‐healing rate in treating moderate‐to‐severe UC patients 4,7,8 . However, approximately 20%–30% of UC patients experience poor treatment response to IFX and disease progression, which further impairs their long‐term clinical outcomes 9,10 . Hence, it is obligatory to identify potential biomarkers to monitor disease progression and predict IFX efficacy in UC patients.…”

Therapeutic drug monitoring for biological medications in inflammatory bowel disease

“…Several factors may affect trough concentrations of these medications, including disease subtype, extent, phenotype, degree of inflammation, serum albumin, concomitant immunomodulator, patient's sex, and body mass index. [ 5 6 7 ] In clinical care, TDM can be performed proactively or reactively. In reactive TDM, serum drug level and presence of ADA are measured in patients receiving a biological agent, in response to evidence of active disease or incomplete response to the biologic that is confirmed with objective evidence via endoscopy, biochemically, or radiographically.…”