Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials

Kristin K Jørgensen, Guro L Goll, Joe Sexton, Nils Bolstad, Inge C Olsen, Øivind Asak, Ingrid P Berset, Ingrid M Blomgren, Katrine Dvergsnes, Jon Florholmen, Svein O Frigstad, Magne Henriksen, Jon Hagfors, Gert Huppertz-Hauss, Espen A Haavardsholm, Rolf A Klaasen, Bjørn Moum, Geir Noraberg, Ulf Prestegård, Jan H Rydning, Liv Sagatun, Kathrine A Seeberg, Roald Torp, Cecilia Vold, David J Warren, Carl M Ystrøm, Knut E A Lundin, Tore Kvien, Jørgen Jahnsen, Kristin K Jørgensen, Guro L Goll, Joe Sexton, Nils Bolstad, Inge C Olsen, Øivind Asak, Ingrid P Berset, Ingrid M Blomgren, Katrine Dvergsnes, Jon Florholmen, Svein O Frigstad, Magne Henriksen, Jon Hagfors, Gert Huppertz-Hauss, Espen A Haavardsholm, Rolf A Klaasen, Bjørn Moum, Geir Noraberg, Ulf Prestegård, Jan H Rydning, Liv Sagatun, Kathrine A Seeberg, Roald Torp, Cecilia Vold, David J Warren, Carl M Ystrøm, Knut E A Lundin, Tore Kvien, Jørgen Jahnsen

Abstract

Background: The NOR-SWITCH main and extension trials demonstrated that switching from originator to biosimilar infliximab (CT-P13) is efficacious and safe across six diseases. However, a subgroup analysis of Crohn's disease (CD) in the main trial displayed a close to significant difference favouring originator infliximab, and more scientific data have therefore been requested.

Objective: The aim was to assess treatment efficacy, safety, and immunogenicity in an explorative subgroup analysis in CD and ulcerative colitis (UC) in the NOR-SWITCH trials.

Patients and methods: The 52-week, randomised, non-inferiority, double-blind, multicentre, phase 4 NOR-SWITCH study was followed by a 26-week open extension trial where all patients received treatment with CT-P13. Treatment efficacy, safety, and immunogenicity in CD and UC were assessed throughout the 78-week study period.

Results: The main and extension trials included 155 and 93 patients with CD and 93 and 80 patients with UC, respectively. Demographic and baseline characteristics were comparable in both treatment arms within patient groups. There were no differences in the main and extension trials regarding changes in activity indices, C-reactive protein, faecal calprotectin, patient's and physician's global assessment of disease activity and patient-reported outcome measures in CD and UC. Moreover, comparable results were also demonstrated for trough serum levels, presence of anti-drug antibodies, and reported adverse events.

Conclusion: Efficacy, safety, and immunogenicity of both the originator and biosimilar infliximab were comparable in CD and UC in the NOR-SWITCH main and extension trials. These explorative subgroup analyses confirm that there are no significant concerns related to switching from originator infliximab to CT-P13 in CD and UC.

Trial registration: ClinicalTrials.gov, number NCT02148640.

Conflict of interest statement

KKJ reports personal fees from Intercept, Norgine, and Celltrion. GLG reports personal fees from AbbVie, Biogen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Orion Pharma, Celltrion, and Boehringer Ingelheim. NB reports personal fees received from Orion Pharma, Roche, Napp Pharmaceuticals, Pfizer, and Takeda. ICO reports grants from the Norwegian Ministry of Health and Care Services during the conduct of the study and personal fees from Pfizer. EAH reports grants from AbbVie, Pfizer, UCB, Roche, and MSD. IPB reports personal fees from AbbVie, MSD, Takeda, Hospira, and Ferring. KEAL reports grants from MSD and personal fees from Takeda, Orion, AbbVie, Pfizer, and MSD. JJ reports personal fees from MSD, AbbVie, Celltrion, Orion Pharma, Takeda, Napp Pharm, AstroPharma, Hikma, and Pfizer. TK reports grants from the Norwegian Ministry of Health and Care Services during the conduct of the study and personal fees from AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, and UCB Pharma. SOF reports personal fees from Takeda, Pharmacosmos, Tillotts, Janssen, Intercept, and Pfizer. The remaining authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Patient disposition in IBD in the NOR-SWITCH main and extension study. CD Crohn’s disease, IBD inflammatory bowel disease, IFX infliximab, PPS per-protocol set, UC ulcerative colitis. 1 Four CD patients withdrew consent, two CD and one UC patients had major change in immunosuppressive treatment, two CD patients were unblinded during the study, two CD patients developed adverse events, and one CD patient was excluded for other reasons. 2 Seven CD and four UC patients withdrew consent, two CD and five UC patients had major change in immunosuppressive treatment, two CD patients were unblinded during the study, one CD and two UC patients developed adverse events, three CD patients and one UC patient were excluded for other reasons
Fig. 2
Fig. 2
Secondary efficacy endpoints in Crohn’s disease from randomisation in main study (baseline/week 0) to study end (week 78), per-protocol set. IFX infliximab
Fig. 3
Fig. 3
Secondary efficacy endpoints in ulcerative colitis from randomisation in main study (baseline/week 0) to study end (week 78), per-protocol set. IFX infliximab

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