Quantification Assays Optimized for Remicade Can Be Used to Monitor Biosimilar Flixabi

Therapeutic drug monitoring (TDM) is increasingly considered a key step to optimizing anti—tumor necrosis factor (anti-TNF) treatment in patients with inflammatory bowel disease (IBD). The advent of biosimilars to Remicade (reference infliximab) creates the necessity of validating the utilization of Remicade-quantifying assays, which are optimized for Remicade, with biosimilar compounds.

A recent study published in Therapeutic Advances in Gastroenterology found that 3 quantification assays optimized for TDM of Remicade can be used to monitor levels of the infliximab biosimilar Flixabi (sold in the United States as Renflexis).

Portuguese researchers, led by Fernando Magro, MD, PhD, and colleagues, previously demonstrated that a number of Remicade quantification methods can be safely applied to quantify Remsima. This study extends those analyses to include Flixabi.

In addition, the researchers assessed the reactivity of anti-Remicade and anti-Remsima sera to Remicade and to its biosimilars, and showed that the anti-Remicade and anti-Remsima sera reacted to the different drugs in a similar fashion. Thus, the researchers determined the existence of Remicade, Flixabi, and Remsima cross-immunogenicity, which supports their high similarity and prevents their switching in nonresponders with antidrug antibodies.

The researchers generated sera of known concentrations of Remicade, Remsima, and Flixabi by diluting the appropriate amount of each drug into a pool of sera extracted from donor controls. Each spiked concentration was repeated between 6 and 9 times and analyzed in duplicate.

Samples were then quantified using 3 different Remicade-quantification assays: an in-house ELISA assay and 2 commercially available kits—the Quantum Blue infliximab quantitative lateral flow assay (Buhlmann; Schonenbuch, Switzerland) and the RIDASCREEN IFX monitoring (R-Biopharm, AG; Darmstadt, Germany).

All tested Remicade-infliximab-optimized assays measured Flixabi as accurately as they measured Remicade and Remsima, with intra-class correlation coefficients between theoretical and measured concentrations varying from 0.920 to 0.990. Inter-assay agreement values for the same compounds were high (intra-class correlation coefficients varied from 0.936 to 0.995).

“This study is, to our knowledge, the first to demonstrate that Remicade-optimized quantification methods can be used to measure Flixabi levels, while consolidating the previously published results concerning Remsima in this context,” the researchers conclude. “In fact, our results suggest that either R-Biopharm, Buhlmann, and the described in-house method can be used to measure Remicade biosimilars Remsima and Flixabi in an accurate fashion.” They said their findings demonstrating the existence of cross-immunogenicity between Remicade, Remsima and Flixabi is a finding that not only reinforces the similarity among these drugs, but also has some clinical implications: “Apatient medicated with Remicade or Remsima whose therapy fails due to the presence of anti-drug antibodies would not benefit from switching to Remicade, Remsima, or Flixabi.”

Reference

Magro F, Rocha C, Viera AI, et al., on behalf of the Portuguese IBD Study Group (GEDII). The performance of Remicade-optimized quantification assays in the assessment of Flixabi levels. Ther Adv Gastroenterol.2018;11:1-9. doi: 10.1177/ 1756284818796956.