Utility of Measuring Infliximab Drug Levels and Anti-Drug Antibodies in Clinical Practice: A Large IBD Referral Centre Experience
Introduction: The development of infliximab (IFX) drug level and anti-drug antibody (ADA) testing has allowed a personalised approach to IFX use in inflammatory bowel disease (IBD). We present our 2-year experience at a tertiary IBD centre.
Method: All IFX drug and ADA levels measured in patients managed at the Guy’s and St. Thomas’ IBD centre were reviewed. Indications for carrying out drug levels, subsequent changes in management and long-term outcomes were evaluated.
Results: 330 levels were measured in 199 patients from May 2012 to October 2014. Median IFX levels were 4.1 (range 0- >8 μg/ml). 109 (33%) levels were sub therapeutic (£2.0 μg/ml), of which 61 patients were symptomatic. This resulted in a change in management in 44 (72%) of those patients. ADA were detected in 22 tests (7%) from 19 patients. 12 patients were switched to adalimumab of which 11 continue (median 11 months follow-up) and 1 was a primary nonresponder. 4 patients continued on IFX but were optimised on thiopurines, only 1 of which had a subsequent improvement in disease activity. 1 patient stopped anti-TNF therapy due to demyelination, and 2 discontinued anti-TNF to take part in clinical trials. 121 levels (37%) were measured in patients with loss of response (LOR) of whom 50 (41%) had sub therapeutic levels (<2.0 μg/ml). 27 patients, all with no detectable antibodies, underwent dose escalation. 32 levels (10%) were measured at week 14 after standard induction of IFX resulting in 3 patients being switched to adalimumab (Ada) due to significant antibody detection (>200 U/ml) and 1 patient having their dose increased to 10 mg/kg due to borderline levels (2.0 μg/ml) along with poor clinical response. 97 levels (29%) were measured as part of annual reassessment resulting in only 8 changes in management. 1 patient with levels >8 μg/ml had a de-escalation from 10 to 5 mg/kg and 3 had their dose increased due to low levels. As a result of inactive disease, 4 out of the 81 patients with therapeutic IFX levels were able to be withdrawn. The remaining levels were measured after a change in dose of IFX (17%) or for consideration of: withdrawal of concomitant immunosuppression (1%), dose reduction (3%) and withdrawal from IFX (3%).
Conclusion: IFX drug and antibody level testing is being increasingly used in clinical practice. The benefits seem greatest in patients with LOR although our understanding of their utility in other circumstances is increasing.
