Antibodies to the innovator infliximab drug Remicade found in rheumatoid arthritis and spondyloarthritis patients also cross-react with the infliximab biosimilar CT-P13, marketed as Remsima or Inflectra, suggesting that switches from the innovator drug to the biosimilar are not advisable in the presence of anti-infliximab antibodies.
Switching an antibody-positive patient from the innovator drug to the biosimilar could mean that existing infliximab antibodies will “interact with the new drug, enhance clearance, and potentially lead to loss of response and infusion-related reactions,” wrote first author M. Begoña Ruiz-Argüello, Ph.D., an employee of the molecular biology testing company Progenika-Grifols in Derio, Spain, and colleagues (Ann Rheum Dis. 2016 Mar 10. doi: 10.1136/annrheumdis-2015-208684).
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In the current study, the investigators set out to discover whether anti-Remicade antibodies cross-reacted with the biosimilar CT-P13, which was approved by the European Medicines Agency in 2013 for the same indications as the originator infliximab biologic Remicade.
They retrospectively selected 250 patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) who were treated with Remicade and 77 control patients who were infliximab naive.
Antibodies to infliximab were measured at the same time using three bridging ELISA assays: one that used Remicade to detect antibodies (Promonitor-ANTI-IFX kit, Progenika-Grifols, Spain); one that used Remsima (Orion Pharma, Norway); and another that used Inflectra (Hospira, United States).
Overall, 126 (50.4%) patients tested positive for antibodies using the Promonitor-ANTI-IFX kit.
These patients also tested positive for antibodies when the Remsima and Inflectra assays were used. Median antibody concentrations between the assays were not statistically different (P greater than .05). No significant differences were observed between patients with RA and SpA (P greater than .05) or in patients on concomitant immunosuppressive treatment, such as methotrexate.
Contrary to previous research, patients who tested negative for antibodies with the Promonitor-ANTI-IFX kit also tested negative with the Remsima and Inflectra assays. “Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to [infliximab] are also present in the biosimilar,” the researchers said.
The investigators said that their findings also supported the use of therapeutic drug monitoring before considering switching patients between drugs.
Although the researchers recommended not switching between Remicade and Remsima or Inflectra, a small subanalysis in their study suggests it would be okay to switch from adalimumab to the infliximab biosimilar. A control population of 19 patients involved in the study who were anti–adalimumab antibody positive tested negative for antibodies to infliximab across the three assays.
Six of the authors are full-time employees of Progenika Biopharma S.A., maker of the Remicade assay used in the study.