Remicade and Its Biosimilars: What Role Does Therapeutic Drug Monitoring Play?

The recent Food and Drug Administration (FDA) recommendation to approve Remicade (infliximab [IFX]) biosimilars for treatment of certain rheumatic disease has prompted further research into implications of transitioning patients from Remicade to these biosimilars.

Antibodies generated against infliximab (IFX) in Remicade-treated patients may cross-react with the IFX biosimilar drug CT-P13 (marketed as Infectra or Remsima), according to research published in Annals of Rheumatic Disease.

Researcher M. Gegona Ruiz-Arguello, PhD, and colleagues affiliated with La Paz University Hospital in Madrid, Spain, sought to determine the cross –reactivity of IFX antibodies generated from exposure to Remicade with the antibodies generated against the Remicade-biosimilar CT-P13 (Infectra or Remsima).

In a retrospective analysis of 250 consecutive patients receiving Remicade IFX for the treatment of rheumatoid arthritis (RA) or ankylosing spondylitis (AS) and 77 healthy controls, researchers measured levels of anti-IFX antibodies produced from treatment with either Remicade or its biosimilars via enyme linked immunosorbent assay (ELISA). To determine ELISA cutoff points, 21 serum samples from healthy donors and 37 samples from IFX-naive patients with RA or AS were assayed.

Researchers found that anti-IFX antibodies generated from Remicade treatment cross-reacted with the Remicade biosimilars, suggesting that there may be shared epitopes in the biosimilars and proteins generated in the immune response to Remicade.

Of the study participants examined, 126 (50.4%) patients tested positive for anti-IFX antibodies with the Promonitor branded analysis kit used to analyze antibody response to Remicade. These Remicade-generated antibodies had a median antibody concentration of 57.8 AU/mL, with 100% of these patients testing positive using 2 additional kits, designed to detect antibodies to Remicade biosimilars Inflectra and Remsima (correlation coefficients ≥0.995).

“Anti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima … suggest[ing] that epitopes influencing the immune response to IFX are also present in the biosimilar,” the authors concluded.

“Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response.”

Summary and Clinical Applicability

In this study, patients with RA and AS being treated with Remicade (IFX) generated anti-Remicade IFX antibodies that, in vitro, cross-reacted with Remicade biosimilars Inflectra and Remsima.  

These results are clinically significant because it suggests a potential therapeutic effect when switching patients from IFX-branded Remicade to its biosimilars, as presumably patients receiving IFX-branded Remicade have generated antibodies that may cross react with the biosimilars. These results are limited by the fact that the Promonitor assay kit detecting anti-Remicade antibodies does not detect IgG4. 

However, if results of this study can be further confirmed via additional studies and their impact on clinical outcomes can be defined, there may be a role in monitoring patients for a loss of clinical response once a patient has been transitioned to a biosimilar drug.

The U.S. Food and Drug Administration has recently recommended biosimilars for approval, after evaluating multiple studies showing pharmacokinetic and therapeutic equivalence.  

The researchers conclude that these results “support the utility for therapeutic drug monitoring before a switching strategy is considered.”

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Ruiz-argüello MB, Maguregui A, Ruiz del agua A, et al. Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars. Ann Rheum Dis. 2016; doi: 10.1136/annrheumdis-2015-208684