Background/Purpose: Infliximab (IFX) is the most immunogenic of anti-TNFα drugs available to treat patients with rheumatic diseases. The recent approval of the first infliximab biosimilars in Europe has raised safety and efficacy concerns. Both Inflectra (IFT) and Remsima (RMS), contain exactly the same active molecule produced with the same manufacturing process, but branded differently. One of the main questions is whether patients treated with Remicade (RMC) can be effectively and safely switched to the biosimilar drug. The purpose of the study was to determine if antibodies to infliximab (ATI) in RMC-treated patients cross-react with the biosimilar.

Methods: A total of 256 samples from 256 patients with rheumatoid arthritis (RA) and Spondyloarthritis (SpA) under RMC were retrospectively selected for the study. Serum was collected immediately before the infusion (trough levels) and stored until the analysis. ATI trough levels were measured in parallel with three different bridging ELISA assays: a) Promonitor-ANTI-IFX CE marked kit (Progenika Biopharma SA, Spain) which uses RMC to crosslink patient anti-drug antibodies (ADA); b) the same assay but using RMS, and c) the same assay but using IFT. Briefly, bridging ELISA takes advantage of the two arms of immunoglobulins to crosslink precoated and HRP-conjugated IFX, used as a capture and detection reagent, respectively. The same cut-point (5 AU/mL), as recommended in the kit package insert, was used in the three assays. Spearman´s coefficient and percentages of agreement were used to study the correlation and association between each assay.

Results: In total, 131 samples out of 256 RMC-treated patient samples were tested positive with Promonitor-ANTI-IFX (51.2%, 131 patients). All were ATI-positive when either IFT or RMC bridging assays were used. Only one sample was positive to antibodies to the biosimilars and negative to antibodies against RMC (<5, 5.3 and 7.0 AU/mL of ATI for RMC, IFT and RMS, respectively), with very low ATI levels close to the cut-point, and attributed to experimental variability. Positive and Negative Percentage Agreements were 99.2%/100%, 99.2%/100% and 100%/100%, for RMC vs. IFT, RMC vs. RMS, and IFT vs. RMS, respectively. Spearman´s coefficients were determined to be 0.995, 0.996 and 0.998, for RMC vs. IFT, RMC vs. RMS, and IFT vs. RMS, respectively (p<0.001). This is the first study that demonstrates cross-immunogenicity between RMC and biosimilar molecules in patients with rheumatic diseases. Results are in agreement with previous data in patients with inflammatory bowel diseases.

Conclusion: ATI of RMC-treated patients cross-react with either IFT or RMS. Results suggest that the immune response is elicited by the same epitopes regardless of the molecule nature. ATI-positive patients treated with RMC should not be switched to a biosimilar treatment, since preexisting ATI will interact with the new drug, enhance clearance and potentially lead to loss of response and infusion-related reactions. Results also demonstrate that Promonitor-ANTI-IFX test can be used to monitor ATI in biosimilar-treated patients. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/antibodies-to-infliximab-in-remicade-treated-rheumatic-patients-show-identical-reactivity-towards-biosimilars/