P443 Trough concentration response in infliximab and adalimumab treated children with IBD following treatment adjustment: A pharmacokinetic model.
Levi, R.(1);Matar, M.(1);Zvoluni, M.(1);Shamir, R.(1);Assa, A.(1);
(1)Schneider Children's Hospital, The institute of Pediatric Gastroenterology- Hepatology and Nutrition, Petach Tikva, Israel;
In patients with IBD, data on trough concentration (TC) response to adjustments in anti-TNFα treatment are scarce.
We included pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of TC. Treatment adjustments were detected and subsequent changes in TC were recorded (next infusion for infliximab and up to 8 weeks TC measurement for adalimumab). Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded.
For the entire cohort (86 patients), median age at diagnosis was 13.2 (10.7-14.9) years (Females, 48%; Crohn's disease, 72%). For infliximab, 58 patients had 201 interval changes (98 decrease and 103 increase) and 26 had dose increase. Dose increase resulted in TC change in the same direction but TC changes could not be predicted due to significant variability (p=0.9). This variability could not be attributed to any specific variable.
Interval decrease: Median TC pre adjustment was 4.3 mcg/ml (IQR, 3.1-6.9 mcg/ml). For every 10% decrease in interval, TC was increased by 1.6 mcg/ml (B= 1.6, 95% CI; 0.9-2.4; p<0.001) or by 57.2% (B=57.2, 95% CI;12.8-124.6; p=0.014). The presence of perianal disease was associated with attenuated response to interval decrease (diminished TC increase), p=0.001. Interval increase: Median TC pre change was 12.6 mcg/ml (IQR, 9.5-12.1 mcg/ml). For every 10% increase in interval, TC was decreased by 0.66 mcg/ml (B= 0.66, 95% CI; 0.2-1.2; p=0.01) or by 4.2% (B= 4.2, 95% CI; 2.0-6.4; p<0.001). The diagnosis of Crohn’s disease (VS. diagnosis of UC) was associated with reduced response to interval increase (diminished TC decrease), p=0.012.
For adalimumab, 28 patients had 31 events of interval decrease from every 2 weeks to every week and 12 events of interval increase back to every 2 weeks. Interval decrease resulted in increased median TC from 4.5 (3.5-5.3) mcg/ml to 8.1 (6.5-10.5) mcg/ml (X1.8) while interval increase resulted in TC change from 15.5 (12.8-18.6) mcg/ml to 9.7 (6.5-14.6) mcg/ml (:1.6). Changes in adalimumab TC were consistently significant (p<0.001). Increase in delta TC was associated with younger age (p=0.018), lower body surface area (p<0.001) and with the absence of perianal disease (p=0.001).
Laboratory measures (CRP, albumin- mostly within normal limits) were not associated with TC response for both agents.
Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab but not for infliximab. Thus, following infliximab adjustment, TC should be measured in-order to assess adequate TC response.