Proactive Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease Patients Receiving Infliximab and Biosimilars

Background:
Inflammatory bowel disease (IBD) in children has become more prevalent in the past decade. Infliximab and its biosimilars use in pediatric IBD have increased. Therapeutic drug monitoring (TDM) is used for treatment adjustments when low drug levels or high antibodies to Infliximab are detected. Due to limited data on Biosimilar and infliximab drug monitoring in pediatric IBD, this study aimed to monitor proactive drug and antibody levels and how it may guide the treatment.
Methods:
This retrospective chart review identified 97 pediatric patients (ages 2-22) with IBD receiving Infliximab or biosimilars. 48 patients who had normal drug levels and no antibodies were not included in the study. The remaining 49 were separated into 2 groups. Group A included 42 patients with initial low drug levels (< 8 ug/mL) and normal antibody levels (< 25); 25 on Infliximab, and 17 on a Biosimilars. Group B included 6 patients with both low drug levels and high antibodies; 2 on Infliximab, and 4 on a Biosimilars. 1 additional patient reported normal drug levels but high antibodies. All patient data was collected over time as their treatments were modified (increased dosage, decreased frequency, both, or adjuvant methotrexate).
Results:
In Group A, after treatment modifications 31 patients reached remission-desirable levels (RDL), marked by normal or high drug levels and no antibodies. The remaining 11 had low drug levels (10), or both (1). 3 out of 10 patients in Group A with low drug levels (drug levels between 2.6 - 5.8 ug/mL) had no treatment modification. Of these, 2 reached RDL, while 1 still had low drug levels. This suggests RDL is attainable without treatment modification for some with low drug levels but normal antibody levels. 7 patients (5 from Group A and 2 from Group B) stopped treatment and switched to another biologic treatment based on undesirable drug levels or antibodies. In Group B 3 patients reached RDL, all had normal or high drug levels and high antibodies. Thus, for those with high antibody levels, TDM and treatment modification were not clearly beneficial. 5 of these 6 patients had combined modifications, while 1 had only a dosage increase. The mean drug level increased from 4.17 ug/mL to 14.11 ug/mL at final TDM, indicating that treatment modifications positively impacted drug levels. However, the mean initial and final antibody levels (11.33 and 33.39, respectively) suggest a more complex relationship. Methotrexate was used as adjuvant therapy in 9 patients (8 in Group A and 1 in Group B) But its effectiveness could not be determined due to simultaneous treatment modification.
Conclusions:
Of the 49 patients in this study, 67.34% achieved RDL, suggesting that proactive TDM is effective in optimizing treatment. Treatment modifications are ultimately the key as this study’s results highlight that each patient is unique. One cannot say that all patients should have their dosage increased, frequency decreased, or an adjuvant added. One must take each patient on a case-by-case basis and use TDM to personalize treatment.