Assays Used to Monitor Infliximab Are Similarly Effective for Biosimilars SB2, CT-P13

Investigators said they have determined that assays used to evaluate circulating drug levels and antibody resistance for the Remicade version of infliximab are also appropriate for 2 infliximab biosimilars, SB2 (Renflexis) and CT-P13 (Inflectra).

The quantitative comparison study compared 4 different, commercially available enzyme-linked immunosorbent assays (ELISAs) used in therapeutic drug monitoring (TDM) to detect drug concentration and antibodies to infliximab (ATIs) in samples of drug diluted in serum. The findings showed the measurements for SB2 and CT-P13 were “comparable to those of the reference infliximab” for each of the assays, the authors wrote.

“The therapeutic drug monitoring required for infliximab therapy can be adequately performed with the biosimilars using the kits currently in use or available in clinical laboratories,” they concluded.

TDM is the measurement of specific drugs and their breakdown by analyzing serum trough levels at timed intervals. Measurements help to guide adjustments in treatment intensity to minimize the risk of treatment failure.

Variability in circulating drug levels is attributed to drug metabolism, leakage through the intestinal wall, or formation of antibodies against the drug. Commercial assays that measure antibodies to infliximab are routinely used as part of drug monitoring.

The biosimilars SB2 and CT-P13 are approved for treatment of inflammatory bowel disease (IBD) in Canada. Although they are structurally different from infliximab, they exhibit similar physicochemical characteristics, pharmaceutical effectiveness, and immunogenicity.

Renflexis and biosimilars SB2 and CT-P13 attack tumor necrosis factor, a cytokine responsible for inflammation affecting patients with ulcerative colitis and Crohn disease. TNF inhibitors are antibodies injected into the blood stream to attack and block TNF's ability to communicate with cells, causing a reduction in inflammatory symptoms.

Development of ATIs alters circulating drug levels by making the drug inactive or increasing the rate of elimination. This makes it important to be able to know the levels of ATI.

Biosimilars to Remicade are associated with cost savings, but it must be possible to reliably monitor for circulating drug and antibody resistance, the authors wrote. The 4 assay kits used for observation were Immunodiagnostik (ALPCO), Ridascreen, Lisa Tracker, and Promonitor.

Two testing labs were used to evaluate results. The drug concentrations tested were based on the analytical measuring range of the assays and the therapeutic range of the drugs. Investigators said the assays demonstrated an acceptable linearity in the tested range for the reference biologic as well as for SB2 and CT-P13.

Although the 4 assays were originally developed for Remicade measurement, investigators said the slopes calculated through Deming regression varied by less than 10% across the three biologics for a given assay. “This gives a bias between the reference infliximab and biosimilars that is less than the usual analytical variability allowable,” suggesting that the slope variations were clinically insignificant, the authors wrote.

Researchers stress that the same evaluations should be made as other biosimilars become available, such as for adalimumab, another TNF inhibitor used to treat IBD. “Analytically biased quantification of biosimilars could lead to inappropriate dose adjustments and harm the patient.”

Reference

Neveu B, Kunst A, Prosser, C, Robitaille R. An in vitro comparison of four different immunoassays for the monitoring of Infliximab biosimilars drug levels [published online January 23, 2020]. Clin Biochem. doi: doi: 10.1016/j.clinbiochem.2020.01.006.