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P633 Antibodies to infliximab in patients treated with either the reference biologic or the biosimilar CT-P13 show identical reactivity towards biosimilars CT-P13 and SB2 in inflammatory bowel disease

Fiorino G.*1, Ruiz-Agüello M.B.2, Maguregui A.2, Nagore D.2, Radice S.1, Gilardi D.1, Correale C.1, Allocca M.1, Furfaro F.1, Alfieri M.1, Martínez A.2, Danese S.1,3

1Humanitas Clinical and Research Center, Department of Gastroenterology, Milan, Italy 2Progenika Biopharma SA, R&D Department, Derio, Spain 3Humanitas University, Department of Biomedical Sciences, Milan, Italy

Background

The recent approvals of the infliximab (IFX) biosimilars, CT-P13 (Remsima®/Inflectra®, Celltrion/Hospira) and SB2 (Flixabi®, Biogen) by EMA were based on robust biosimilarity comparisons that demonstrated their equivalent efficacy and comparable safety and immunogenicity with the reference biologic (Remicade®, RMC, Merck). However, concerns about inter-switching patients between the three brands were understandably raised in the absence of cross reactivity data between the antidrug antibodies against each molecule with the other two. We aimed to determine if antibodies to IFX (ATI) in IBD patients cross-react with CT-P13 and SB2.

Methods

Sera from patients who participated in BIOSIM01 (an observational retrospective study in which patients were treated with either RMC only, or CT-P13 only or RMC followed by a switch to CT-P13) were used. Based on previous ATI status 34 (13 RMC, 9 CT-P13, and 12 switchers) out of the 103 patients (59 CD and 44 UC) enrolled, were selected. Additionally, 28 IFX-naïve patients were tested as controls. In total, 180 samples were analysed. ATI trough levels were measured in parallel with 3 different bridging ELISA: a) Promonitor-ANTI-IFX kit (Progenika, Spain) which uses RMC to crosslink patient anti-IFX antibodies; b) the same assay but using CT-P13, and c) the same assay but using SB2. Spearman's coefficient and percent of agreement were used to study the correlation and association between assays.

Results

In total, 76 samples out of 152 IFX-treated patient samples were tested positive with Promonitor-ANTI-IFX (30 RMC, 14 CT-P13 and 32 switchers). All were ATI-positive when either CT-P13 or SB2 bridging assays were used. Positive and Negative Percent Agreements were 100% and 100%,respectively, when they were compared either with CT-P13 or SB2 bridging assays. No significant differences were found among ATI level determined by the three assays, with Spearman's coefficients ranging between 0.98 to 1.0 for all the three groups of patients (p<0.0001) (Table 1).

Conclusion

ATI of RMC-, CT-P13- or RMC to CT-P13 switch patients show full cross-reactivity with SB2 and with CT-P13 [1,2]. No significant differences are observed in ATI levels determined with either drug, suggesting that immunodominant epitopes in the reference and CT-P13 drugs are equally present in SB2, and are responsible for exactly the same degree of reactivity. Results also demonstrate that Promonitor-ANTI-IFX test can be used to monitor antibodies to CT-P13 or SB2 in biosimilar-treated patients.

References:

[1] Ruiz-Arguello MB, (2016), Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity towards biosimilars, Ann Rheum Dis, 1693–6, 75

[2] Ben-Horin S, (2016), Cross-immunogenicity: antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima, Gut, 1132–8, 65