P1147 Proactive therapeutic drug monitoring of infliximab leads to durability of treatment in children with Inflammatory Bowel Disease
Authors: Chuah C W , Eldredge J , Magoffin A , O'Loughlin E V , Park C J , Puppi J , Siew S , Stormon M , Thacker K , Dutt S 
Published: January 2025

Abstract

Background
On standard dosing of infliximab (IFX), one third of patients will develop secondary loss of response (LOR) by the first year and up to 50% of initial responders will develop LOR by 5 years.1 Sustained high trough levels and dose escalation are proven to increase the durability of infliximab.2 The role of proactive therapeutic drug monitoring (TDM) to guide this remains controversial. In 2019, our unit opted for proactive TDM (at week 6, week 14 and 6 monthly thereafter) as standard therapy to guide dose escalation in maintenance. We report the outcomes of our patient cohort over 2 years from initiation of IFX.

Methods
A retrospective chart review was performed between 01/01/2019 to 31/12/2021. All patients with IBD who received IFX were included. Patients with acute severe colitis were excluded as treatment protocol was different. Data on demographics, disease characteristics, immunomodifier, IFX dosing, frequency, drug and antibody levels were collected and analysed. Primary outcome was switching to different biologic as a marker of treatment failure. Standard IFX dosing is 5mg/kg IVI at 0, 2, 6 weeks for induction and 8 weekly in maintenance. The dose was escalated if week 6&lt;15µg/mL, week 14/maintenance &lt;5µg/mL, or &lt;10µg/mL in stricturing/fistulising disease.

Results
98 patients (58% male) were identified, 82% had Crohn’s disease (CD) and 18% Ulcerative Colitis (UC). Median age at diagnosis was 11 years old, and 12.5 years old at starting IFX. 81% received an immune modifier of which 64% had methotrexate and 39% azathioprine. 13% received escalated induction and 77% received escalated maintenance. The median week 6 level of standard vs escalated maintenance group was 22.8µg/mL vs 12.4µg/mL (p=0.01). 3% did not respond to induction and were discontinued. 2% developed IFX antibodies. At 1 year, 5% of CD and 22% of UC patients switched to a different biologic and at 2 years this was 13% and 44% respectively. Median time to switch was 53 weeks. Switching to alternate biologic was associated with escalated induction OR 5.2 (p&lt;0.01) UC phenotype OR 5.6 (p&lt;0.01) and concomitant steroid use OR 5.2 (p&lt;0.04).

Conclusion
Our week 6 IFX level guided clinician decision to escalate dosing in maintenance. The outcomes for our cohort show good treatment durability particularly in CD, 95% at 1 year and 87% at 2 years, which is better than what has been reported.2 Patients with severe phenotype remain poor responders and difficult to treat as evident by receiving escalated induction, i.e escalation without TDM, and steroid use being predictors. This study adds to the growing body of evidence of the role of proactive TDM in increasing durability of IFX.

References
1.Ding, N. S., Hart, A., & De Cruz, P. (2016). Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management. Alimentary pharmacology & therapeutics, 43(1), 30–51. https://doi.org/10.1111/apt.13445
2.Vahabnezhad, E., Rabizadeh, S., & Dubinsky, M. C. (2014). A 10-year, single tertiary care center experience on the durability of infliximab in pediatric inflammatory bowel disease. Inflammatory bowel diseases, 20(4), 606–613. https://doi.org/10.1097/MIB.0000000000000003