Background The first infliximab (IFX) biosimilar (CT-P13) in Europe is marketed as two brand names, Inflectra (IFT) and Remsima (RMS), that contain the same IFX molecule produced with the same manufacturing process. One of the main questions is whether patients treated with Remicade (RMC) can be effectively and safely switched to CT-P13.
Objectives To determine if antibodies to infliximab (ATI) in RMC-treated patients cross-react with CT-P13.
Methods Consecutive patients (250) with active rheumatoid arthritis (RA) and spondyloarthritis (SpA) under RMC treatment and never exposed to CT-P13, were retrospectively selected according to clinical information and anti-drug antibody (ADA) status. 37 IFX-naïve rheumatic patients, 19 IFX-naïve rheumatic patients with anti-adalimumab antibodies (AAA), and 21 healthy individuals were assayed as controls. ATI trough levels were measured in parallel with three different ELISA assays: #1 Promonitor-ANTI-IFX (Progenika, Spain) which uses RMC to crosslink patient ADA; #2 the same assay but using RMS, and #3 the same assay but using IFT.
Results In total, 126 samples out of 250 Remicade-treated patient samples were tested positive with Promonitor-ANTI-IFX (50.4%, 131 patients). All were ATI-positive when either IFT or RMC bridging assays were used (Fig1). Positive and Negative Percent Agreements were 100%/100% for any comparison: RMC vs. IFT or RMC vs. RMS or 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). No differences between RA and SpA, or between concomitant immunosuppressives, were observed. This is the first study that demonstrates cross-immunogenicity between RMC and a biosimilar molecule in patients with rheumatic diseases. Results are in agreement with previous data in patients with inflammatory bowel diseases1.
Conclusions ATI of RMC-treated patients cross-react with either IFT or RMS. Results suggest that the epitopes raising the immune response to the innovator drug are responsible for the same degree of reactivity when sera are confronted to the biosimilar molecule, although it must be noted that the biosimilar might present new epitopes due to different glycosylation pattern or impurities, and even conformational epitopes due to potential aggregations. 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. Further studies with biosimilar-treated patients are warranted to increase our knowledge about potentially different immunogenic responses. Results also demonstrate that Promonitor-ANTI-IFX test can be used to monitor antibodies to CT-P13 in biosimilar-treated patients. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.
Ben-Horin S et al Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima. Gut 2015 [Epub ahead of print]
Disclosure of Interest B. Ruiz-Argüello Employee of: Employee of Progenika Grifols, A. Maguregui Employee of: Employee of Progenika Grifols, A. Ruiz del Agua Employee of: Employee of Progenika Grifols, D. Pascual-Salcedo: None declared, A. Martínez: None declared, T. Jurado: None declared, C. Plasencia: None declared, A. Balsa: None declared, J. Rosas: None declared, F. Llinares-Tello: None declared, N. Torres Employee of: Employee of Progenika Grifols, A. Martínez Employee of: Employee of Progenika Grifols, D. Nagore Employee of: Employee of Progenika Grifols