Immunogenicity of Originator and Biosimilar Infliximab: Anti-Drug Antibody Occurence, Cross-Reactivity and Epitope Specificities across Six Diseases. Analyses from a Norwegian Randomized Switching Trial

Guro Løvik Goll¹, Nils Bolstad², Ines Iria^3,4, Rolf Klaasen⁵, Kristin Kaasen Jørgensen⁶, Inge C Olsen⁷, Ana Valido⁸, Maria J Saavedra⁹, João E. Fonseca¹⁰, Merete Lorentzen¹¹, Cato Mork¹², Knut EA Lundin¹³, David J Warren¹⁴, Espen A. Haavardsholm¹⁵, Jorgen Jahnsen¹⁶, Tore Kvien¹⁵ and João Gonçalves¹⁷, ¹Department of Rheumathology, Diakonhjemmet Hospital, Oslo, Norway, ²Department of Medical Biochemistry,, OUS-Radiumhospitalet, Oslo, Norway, ³Dept Pharmacology, Faculdade de Farmacia da Universidade de Lisboa, Lisbon, Portugal, ⁴iMed- Research Institute for medicines, Lisbon, Portugal, ⁵Dartment of Medical Biochemistry, OUS-Radiumhospitalet, Oslo, Norway, ⁶Dept Gastroenterology, Akershus University Hospital, Lørenskog, Norway, ⁷Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ⁸Rheumatology, Centro Hospitalar Lisboa Norte, Lisbon, Portugal, ⁹Rheumatology and Metabolic Bone Diseases, Hospital de Santa Maria, CHLN, Lisbon, Portugal, ¹⁰Serviço de Reumatologia e Doenças Ósseas Metabólicas, Hospital de Santa Maria, CHLN, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal, ¹¹Dept of Dermatology, Rikshospitalet, Oslo, Norway, ¹²Dept of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, ¹³Dept of gastroenterology, Oslo University Hospital, Oslo, Norway, ¹⁴Department of Medical Biochemistry, OUS-Radiumhospitalet, Oslo, Norway, ¹⁵Dept. of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, ¹⁶Dept of Gastroenterology, Akershus University Hospital, Lørenskog, Norway, ¹⁷Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Antibodies, Biologic drugs, biosimilars and infliximab

Session Information

Date: Sunday, October 21, 2018

Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster I: Imaging, Clinical Studies, and Treatment

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

The NOR-SWITCH study was funded by the Norwegian government to investigate switching from originator infliximab (INX) to biosimilar CT-P13, in spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (Ps), Crohn’s disease (CD) and ulcerative colitis (UC). Previously, the primary analyses of the pooled indications have been published¹. Anti-drug antibodies (ADAb) are associated with treatment failure and have been a concern in switching. Here, we investigate immunogenicity of infliximab in patients treated with originator INX vs patients switched to CT-P13; between patients with different inflammatory diseases; and the epitope specificities of ADAb.

Methods:

The study was a 52-week randomized, double-blind, non-inferiority, phase IV trial and included adult patients with SpA, RA, PsA, UC, CD or Ps on originator INX. Patients were randomized 1:1 to either continued INX or switch to CT-P13 treatment. Assays for drug serum levels and neutralizing ADAb are fully automated on the AutoDELFIA® (PerkinElmer, Waltham, MA) immunoassay platform. Immunogenic infliximab-epitopes were identified by ELISA and comparison of sera from patients with CD, UC, SpA, RA, PsA or Ps was performed.

Results:

20 patients entered the study with detectable ADAb (9 in INX arm, 11 in CT-P13 arm). 36 patients (17 in INX-arm, 19 in CT-P13 arm) developed incident ADAb during the 52-week main study period with no consistent difference between diseases though numbers are small. 36 patients’ and 15 control sera were tested for epitope specificity. No Ps patients developed ADAbs in our study. All anti-CT-P13 and anti-INX sera were cross-reactive with INX and CT-P13, respectively. ADAb concentrations against INX or CT-P13 were strongly correlated (r values 0.92 – 0.99, p<0.001 for all experiments, Spearman’s correlation test). ADAb-negative controls (10 healthy individuals, 5 patients with RA) were negative for both INX and CT-P13. Recognition of 5 different batches of CT-P13 and INX by IgG4 ADAb were similar between all tested sera. ADAb in 60%-79% of patients recognized 7 synthetic peptides, with no significant differences between CT-P13 and INX ADAb. However, two epitopes were specifically recognized in UC and CD but not in rheumatic patients. Patients with detectable ADAb at any time were more likely to discontinue study drug treatment (7/26 (26.9 %) in INX arm, 5/30 (16.7 %) in CT-P13 arm) than patients without detectable ADAb (17/214 (7.9 %) in INX arm, 13/210 (6.2 %) in CT-P13 arm) (p=0.001).

Studies on a possible association between HLA and ADAb responses are ongoing.

Conclusion:

ADAb occured to a similar degree in the two study arms and ADAb to originator INX also recoginized CT-P13. The majority of patients show no consistent difference in epitope specificity between RA, SpA, PsA, UC and CD patients. However, two specific minor epitopes are only recognized by IBD patients which might reflect the importance of HLA background for ADAb response.

¹Jørgensen KK, Olsen IC, Goll GL et al. Switching from originator infliximab to biosimilar CT-P13 compared to maintained treatment with originator infliximab (NOR-SWITCH): a 52-week randomised double-blind non-inferiority trial. The Lancet, 2017; 389:2304-16.

Disclosure: G. L. Goll, AbbVie, Boeringer Ingelheim, Eli Lilly, Novartis, Pfizer, Orion Pharma, Roche, Sandoz, 5; N. Bolstad, Roche, 5,Orion Pharma, 5,Napp Pharma, 5,Pfizer, Inc., 5,Takeda, 5,Janssen, 5; I. Iria, None; R. Klaasen, None; K. K. Jørgensen, Tillots, Celltrion, Intercept, Sandoz, 5; I. C. Olsen, Pfizer, Inc., 5; A. Valido, None; M. J. Saavedra, None; J. E. Fonseca, AbbVie Inc., 2, 8,Pfizer, Inc., 2, 8,Merck & Co., 2, 8,Bayer, 2, 8,Janssen, 2, 8,Roche, 2, 8,UCB, Inc., 2,Novartis, 2, 8; M. Lorentzen, None; C. Mork, Novartis, 5,LEO Pharma, 5,ACO hud, 5,AbbVie Inc., 5,Galderma Nordic, 5,Cellgene, 5; K. E. Lundin, AbbVie Inc., 5,MSD, 5,Takeda, 5,Orion Pharma, 5,Hospira, 5,Tillots, 5,Bioniz, 5,Immusan T, 5; D. J. Warren, None; E. A. Haavardsholm, Pfizer, Eli Lilly, Janssen-Cilag, Roche, Celegene, Pfizer, UCB, Roche, AbbVie, MSD, EliLilly, 5,Pfizer, UCB, Roche, MSD, AbbVie, 2; J. Jahnsen, Orion Pharma, 5,Celltrion, 5,Janssen, 5,Pfizer, Inc., 5,MSD, 5,AbbVie Inc., 5,Takeda, 5,Napp Pharma, 5,Roche, 5,Boeringer Ingelheim, 5,Astro Pharma, 5,Mundi Pharma, 5,Sandoz, 5; T. Kvien, AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, 5, 8,AbbVie, BMS, MSD, Pfizer, Roche, UCB., 2; J. Gonçalves, AbbVie Inc., 5,Amgen Inc., 5,Biogen, 5,MSD, 5,Pfizer, Inc., 5.

To cite this abstract in AMA style:

Goll GL, Bolstad N, Iria I, Klaasen R, Jørgensen KK, Olsen IC, Valido A, Saavedra MJ, Fonseca JE, Lorentzen M, Mork C, Lundin KE, Warren DJ, Haavardsholm EA, Jahnsen J, Kvien T, Gonçalves J. Immunogenicity of Originator and Biosimilar Infliximab: Anti-Drug Antibody Occurence, Cross-Reactivity and Epitope Specificities across Six Diseases. Analyses from a Norwegian Randomized Switching Trial [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/immunogenicity-of-originator-and-biosimilar-infliximab-anti-drug-antibody-occurence-cross-reactivity-and-epitope-specificities-across-six-diseases-analyses-from-a-norwegian-randomized-switching-tri/. Accessed .

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