Point-of-Care Assays for Infliximab Therapeutic Drug Monitoring in Patients with IBD: Is Quicker Better?

Excerpt

It has been 25 years since the FDA approved infliximab, the first tumor necrosis factor-a (TNF) inhibitor, for treatment of inflammatory bowel disease (IBD). Despite the subsequent introduction of multiple new therapies, treatment failure remains a major cause of morbidity for patients with IBD. Over the last decade, as experience with biologic medications has advanced, therapeutic drug monitoring (TDM) has emerged as a technique for measuring the serum concentration of biologic medications and detecting anti-drug antibodies that are associated with treatment failure [1] with the intent to reduce the risk of primary and secondary non-response. Several studies have investigated different monitoring strategies for biologic treatment of IBD, broadly falling into reactive (in response to clinical deterioration) vs. proactive (TDM regardless of clinical condition) approaches, with conflicting results in many cases as to utility and cost-effectiveness [2‐4]. Though in theory, proactive TDM could prevent loss of response to therapy (vs. reactive TDM which would aim to rescue response in a patient who had relapsed disease), several factors have hindered the wider adoption and analysis of this strategy. Perhaps one of the largest barriers is the infliximab drug concentration is typically measured using an enzyme-linked immunosorbent assay (ELISA) assay that can be time-consuming in some laboratories. To address this, point-of-care (POC) assays were developed to address this issue, with successful use in the detection of anti-drug antibodies, [5] and in a few instances in the measurement of infliximab serum levels, albeit with varying accuracy [6]. Unfortunately, many of the available POC assays rely upon serum input, necessitating additional laboratory equipment over those that can use capillary blood for detection. Valdés-Delgado and colleagues, in an article published in this issue of Digestive Diseases and Sciences [7], assessed two capillary blood-based POC tests (one for anti-drug antibodies, the other for drug concentration) for performance against reference ELISA tests in adult patients with IBD both during induction and maintenance phases of treatment. They performed a prospective observational study in which they assessed a total of 135 blood samples using a POC test that could detect drug levels from capillary blood (Promonitor Quick IFX) with excellent correlation between POC and ELISA (r = 0.84). Consistent with prior work, the POC assay has slightly lower sensitivity than ELISA for anti-drug antibodies [5]. The overall concordance with regard to therapeutic range between ELISA and POC assays was 87.4%, indicating that for the most part clinical decision-making would have been the same when informed by either assay. …