Should a patient already on Infliximab (infliximab) undergo routine testing for Infliximab (infliximab) serum levels and anti-Infliximab (infliximab) antibodies?

From the Guidelines

Patients on infliximab should have their serum levels and antibodies checked routinely, particularly when showing suboptimal response, loss of response, or infusion reactions, to guide treatment decisions and optimize therapy. This approach is supported by the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults 1. The guidelines suggest that measuring drug and antibody levels can help inform treatment decisions, such as intensifying anti-TNF therapy, switching to an alternative biologic, or considering withdrawal of treatment.

Key Considerations

• Testing should typically be performed during maintenance therapy, particularly when patients show suboptimal response, loss of response, or infusion reactions.
• The optimal timing is just before the next scheduled infusion (trough level).
• Target trough levels generally range from 3-7 μg/mL for inflammatory bowel disease and 1-10 μg/mL for rheumatologic conditions, though ideal levels may vary by disease.
• If levels are low with positive antibodies, switching to a different biologic may be necessary.
• If levels are low without antibodies, dose intensification (increasing dose or frequency) is often appropriate.

Evidence-Based Recommendations

• A retrospective analysis of 247 IBD patients with 330 loss of response events showed that measurements of drug and antibody levels could inform the likely outcome of interventions 1.
• A decision analytic model in Crohn’s patients losing responsiveness to infliximab showed that a testing strategy was likely to be cost-effective compared with empiric changes in treatment 1.
• The American Gastroenterological Association Institute technical review on the role of therapeutic drug monitoring in the management of inflammatory bowel diseases also supports the use of therapeutic drug monitoring to guide treatment decisions 1.

Clinical Implications

• Routine monitoring of infliximab serum levels and antibodies can help optimize therapy by allowing personalized dosing adjustments, potentially improving outcomes and reducing unnecessary medication exposure.
• This proactive therapeutic drug monitoring approach is increasingly preferred over reactive testing only when problems arise, as it may prevent loss of response and complications.

From the FDA Drug Label

The incidence of antibodies to infliximab was based on the original EIA method in all clinical studies of infliximab except for the Phase 3 study in pediatric patients with ulcerative colitis where the incidence of antibodies to infliximab was detected using both the EIA and ECLIA methods The incidence of antibodies to infliximab in patients given a 3-dose induction regimen followed by maintenance dosing was approximately 10% as assessed through 1 to 2 years of treatment with infliximab. A higher incidence of antibodies to infliximab was observed in Crohn's disease patients receiving infliximab after drug-free intervals >16 weeks Patients who were antibody-positive were more likely to have higher rates of clearance, reduced efficacy and to experience an infusion reaction

The FDA drug label does not answer the question of whether a patient already on infliximab should routinely do infliximab level (serum level) and infliximab antibodies testing.

From the Research

Monitoring Infliximab Levels and Antibodies

• The clinical efficacy of infliximab is correlated with the levels of infliximab and antibodies to infliximab (ATI) 2.
• Monitoring patients for the trough levels of infliximab and the presence of ATI is very important, as ATI may interfere with the pharmacodynamics and pharmacokinetics of the drug, resulting in a loss of response for a substantial proportion of patients 2.
• The addition of an immunomodulator to infliximab therapy can eliminate antidrug antibodies in serum and restore clinical response of patients with inflammatory bowel disease 3, 4.

Routine Measurement of Infliximab Levels and Antibodies

• There is no optimal assay for monitoring infliximab and ATI levels, and many technical problems need to be solved to make therapeutic drug and immunogenicity monitoring a part of routine clinical management 2.
• Single measurement of ATI titer may be insufficient for predicting therapeutic response due to transient expression of ATI, and multiple measurements may be necessary to detect significant differences between adequate and inadequate responder groups 5.
• Simultaneous measurement of serum infliximab level prior to administration of regular infliximab infusion and ATI titers can significantly increase the diagnostic accuracy for therapeutic decision in patients uncertainly responding to the therapy 5.

Clinical Role of Infliximab Level and Antibody Measurements

• Assessments of bioavailability and immunogenicity of anti-TNF biologicals may be used to optimize dose regimens and prevent prolonged use of inadequate therapy 6.
• Serum infliximab and antibody-to-infliximab levels are objective parameters that may have a great role in the therapeutic decisions during maintenance biological therapy 5.
• The measurement of trough levels of infliximab and ATI titers can help identify patients who may benefit from a change in therapy, such as the addition of an immunomodulator 3, 4.