Clinical Information

Infliximab is a chimeric immunoglobulin (IgG1 kappa) targeting tumor necrosis factor-alpha (TNF-a) and it is currently US Food and Drug Administration (FDA)-approved for the treatment of multiple inflammatory conditions. Infliximab binds to soluble TNF-a and transmembrane homotrimers, which are found on the surface of macrophages and T cells, with similar affinity. Infliximab has the ability to mediate complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity, which leads to the lysis of target cells.

The reference product for infliximab is Remicade (Janssen Pharmaceuticals) and several biosimilar products are FDA-approved, including but not limited to: Renflexis (infliximab-abda, Organon), Inflectra (infliximab-dyyb, Pfizer Inc), Ixifi (infliximab-qbtx, Pfizer Inc), and Avsola (infliximab-axxq, Amgen). Inflectra, Renflexis, and Avsola have the same primary amino acid sequence as Remicade. Therefore, “infliximab” will be used to refer to both the reference product and the biosimilar products interchangeably. This test cannot distinguish between Remicade and the infliximab biosimilar products.

A biosimilar product is a biological product that it is highly similar to an FDA-approved biological product, known as the reference product, but manufactured by a different company. No clinically meaningful differences in terms of safety and effectiveness from the reference product are present. Only minor differences in clinically inactive components are allowable in biosimilar products. In contrast to generic medications, a prescription of biosimilars needs to come from the ordering physician and not the dispensing pharmacy (pharmacies cannot substitute a biosimilar for another medication; a separate prescription is required).

This assay has been verified to measure antibodies to infliximab (ATI) (Remicade and the biosimilars infliximab-dyyb, infliximab-abda, and infliximab-axxq) with no analytical differences between the detection of ATI for the four drugs. It is expected that antibodies developed against other biosimilars would also demonstrate no significant analytical differences for the drug quantitation.

Infliximab pharmacokinetic properties may vary with disease and clearance is affected by concomitant use of immunosuppressants, high concentrations of TNF-a and C-reactive proteins,(1,2) low albumin concentrations, high body mass index, and presence of ATI, also known as human antichimeric antibodies.(3) Male patients seem to clear infliximab faster than female patients.(3)

Several studies have demonstrated that infliximab quantitation in the setting of loss of response to therapy can aid in patient management, as trough concentrations defined as therapeutic have been associated with superior clinical response and improved prognosis.(4-6) Other studies have shown that proactive monitoring of infliximab concentrations in the maintenance stage, even when there is clinical response was more effective in sustaining disease control than standard therapy without any therapeutic drug monitoring in preventing disease worsening during a 52-week period.(7)

Evaluation of infliximab concentrations may be of value for all inflammatory diseases for which it is prescribed. Primary indications for testing of infliximab include loss of response, partial response on initiation of therapy, autoimmune or hypersensitivity reactions, primary nonresponse, reintroduction after drug holiday, endoscopic/computed tomography enterography recurrence (in inflammatory bowel disease), acute infusion reactions and proactive monitoring.

Measurement of infliximab concentrations is indicated at trough, immediately prior to the next scheduled infusion. Infliximab concentrations tend to reach steady state and stabilize after 14 weeks (approximately 100 days). Quantitation of peak infliximab concentrations is strongly discouraged.

Low trough concentrations may be correlated with loss of response to infliximab. Assessment of ATI is suggested when infliximab quantitation at trough is 5.0 mcg/mL or less.