THU0700 Immunogenicity in patients switching from stable originator infliximab treatment to CT-P13: analyses across six diseases from the 52-week randomized nor-switch study

Background TNF-inhibitors (TNFi) have improved treatment of Crohn's disease (CD), ulcerative colitis (UC), spondyloarthritis (SpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and chronic plaque psoriasis (Ps). The NOR-SWITCH study was funded by the Norwegian government to investigate if switching from originator infliximab (Remicade®, INX) to biosimilar CT-P13 (Remsima®), is safe. Previously, the primary analyses of the pooled indications have been published1. Immunogenicity is associated with treatment failure and has been of particular concern in switching 2. Objectives The NOR-SWITCH study aimed to assess if immunogenicity to infliximab differed between patients treated with continous INX vs patients switched to CT-P13. Methods The study was designed as a 52-week randomized, double-blind, non-inferiority, phase IV trial. Adult patients with a diagnosis of CD, UC, SpA, RA, PsA or Ps on stable treatment with the originator infliximab were eligible. Patients were randomized 1:1 to either continued INX or switch to CT-P13 treatment, using unchanged dosing regimen. Trough drug levels and neutralizing anti-drug antibodies (ADAb) measurements were done prior to every infusion, but results were not reported during the study. Assays for drug serum levels and ADAb are fully automated on the AutoDELFIA® (PerkinElmer, Waltham, MA) immunoassay platform. Results Twenty patients entered the study with detectable ADAb (9 in INX arm, 11 in CT-P13 arm). 36 additional patients developed detectable incident ADAb during the 52-week study period (17 in INX arm, 19 in CT-P13 arm). Incident ADAb in each disease are shown in the table. Patients with detectable ADAb at any time during the study period 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). Incident ADAb during study period (total number of patients), Full Analysis Set INX CT-P13 All patients in study 17 (241) 7.1% 19 (240) 7.9% RA patients 6 (39) 15.4% 2 (38) 5.3% SPA patients 2 (45) 4.4% 5 (46) 10.9% PSA patients 1 (14) 7.1% 0 (16) UC patients 5 (47) 10.6% 8 (46) 17.4% CD patients 3 (75) 3.9% 4 (77) 5.2% Ps patients 0 (18) 0 (17) Conclusions The NOR-SWITCH study demonstrated similar immunogenicity in patients switched to CT-P13 vs those who continued INX treatment, supporting that switch does not influence ADAb formation. Presence of ADAb was associated with termination of study treatment. References Jørgensen 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, in press. Dörner T, Kay J. Biosimilars in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol 2015 Dec;11(12):713–24. Disclosure of Interest G. Goll Consultant for: Novartis, Pfizer, Orion Pharma, AbbVie, I. Olsen: None declared, K. Lundin Consultant for: Orion Pharma, MSD, Takeda, K. Jørgensen Consultant for: Orion Pharma, AbbVie, Tillott, Intercept, M. Lorentzen: None declared, R. Klaasen: None declared, D. Warren: None declared, C. Mørk Consultant for: Novartis, LeoPharma, ACOhud, AbbVie, Galderma Nordic, Cellgene, J. Jahnsen Consultant for: Orion Pharma, Celltrion, Pfizer, MSD, AbbVie, Takeda, Napp Pharm, AstroPharma, E. Haavardsholm Consultant for: AbbVie, UCB, Pfizer, MSD, Roche, T. Kvien Consultant for: Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lily, Epirus, Hospira, Merck-Serono, Novartis, Orion Pharma, Pfizer, Sandoz, UCB, N. Bolstad: None declared