Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial

G L Goll; K K Jørgensen; J Sexton; I C Olsen; N Bolstad; E A Haavardsholm; K E A Lundin; K S Tveit; M Lorentzen; I P Berset; B T S Fevang; S Kalstad; K Ryggen; D J Warren; R A Klaasen; Ø Asak; S Baigh; I M Blomgren; Ø Brenna; T J Bruun; K Dvergsnes; S O Frigstad; I M Hansen; I S H Hatten; G Huppertz-Hauss; M Henriksen; S S Hoie; J Krogh; I P Midtgard; P Mielnik; B Moum; G Noraberg; A Poyan; U Prestegård; H U Rashid; E K Strand; K Skjetne; K A Seeberg; R Torp; C M Ystrøm; C Vold; C C Zettel; K Waksvik; B Gulbrandsen; J Hagfors; C Mørk; J Jahnsen; T K Kvien

doi:10.1111/joim.12880

Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial

J Intern Med. 2019 Jun;285(6):653-669. doi: 10.1111/joim.12880. Epub 2019 Apr 12.

Authors

G L Goll¹, K K Jørgensen², J Sexton¹, I C Olsen^{1

3}, N Bolstad⁴, E A Haavardsholm^{1

5}, K E A Lundin^{5

6

7}, K S Tveit⁸, M Lorentzen⁹, I P Berset¹⁰, B T S Fevang¹¹, S Kalstad¹², K Ryggen¹³, D J Warren⁴, R A Klaasen⁴, Ø Asak¹⁴, S Baigh¹⁵, I M Blomgren¹⁶, Ø Brenna¹⁷, T J Bruun¹², K Dvergsnes¹⁸, S O Frigstad¹⁹, I M Hansen²⁰, I S H Hatten²¹, G Huppertz-Hauss²², M Henriksen²³, S S Hoie²⁴, J Krogh²⁵, I P Midtgard²⁶, P Mielnik²⁷, B Moum^{5

28}, G Noraberg²⁹, A Poyan³⁰, U Prestegård³¹, H U Rashid³², E K Strand³³, K Skjetne¹³, K A Seeberg³⁴, R Torp³⁵, C M Ystrøm³⁶, C Vold³⁷, C C Zettel³⁸, K Waksvik³⁹, B Gulbrandsen⁴⁰, J Hagfors⁴¹, C Mørk⁴², J Jahnsen^{2

5}, T K Kvien^{1

5}

Affiliations

¹ Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
² Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
³ Research Support Services CTU, Oslo University Hospital, Oslo, Norway.
⁴ Department of Medical Biochemistry, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
⁵ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁶ Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁷ K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway.
⁸ Department of Dermatology, Haukeland University Hospital, Bergen, Norway.
⁹ Department of Dermatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
¹⁰ Department of Gastroenterology, Ålesund Hospital, Ålesund, Norway.
¹¹ Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
¹² Department of Rheumatology, University Hospital of Northern Norway, Tromsø, Norway.
¹³ Department of Dermatology, Sankt Olav's Hospital, Trondheim, Norway.
¹⁴ Department of Gastroenterology, Gjøvik Hospital, Gjøvik, Norway.
¹⁵ Department of Dermatology, Haugesund Hospital, Haugesund, Norway.
¹⁶ Department of Gastroenterology, Haugesund Hospital, Haugesund, Norway.
¹⁷ Department of Gastroenterology, Sankt Olav's Hospital, Trondheim, Norway.
¹⁸ Department of Gastroenterology, Sørlandet Hospital, Kristiansand, Norway.
¹⁹ Department of Gastroenterology, Baerum Hospital, Baerum, Norway.
²⁰ Department of Rheumatology, Helgelandssykehuset, Mo I Rana, Norway.
²¹ Department of Dermatology, Førde Hospital, Førde, Norway.
²² Department of Gastroenterology, Telemark Hospital, Skien, Norway.
²³ Department of Gastroenterology, Østfold Hospital, Fredrikstad, Norway.
²⁴ Department of Rheumatology, Sørlandet Hospital, Kristiansand, Norway.
²⁵ Department of Rheumatology, Levanger Hospital, Levanger, Norway.
²⁶ Department of Rheumatology, Bodø Hospital, Bodø, Norway.
²⁷ Department of Rheumatology, Førde Hospital, Førde, Norway.
²⁸ Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
²⁹ Department of Gastroenterology, Sørlandet Hospital, Arendal, Norway.
³⁰ Department of Rheumatology, Kongsvinger Hospital, Kongsvinger, Norway.
³¹ Department of Gastroenterology, Lillehammer Hospital, Lillehammer, Norway.
³² Department of Rheumatology, Østfold Hospital, Moss, Norway.
³³ Department of Rheumatology, Revmatismesykehuset, Lillehammer, Norway.
³⁴ Department of Gastroenterology, Vestfold Hospital, Tønsberg, Norway.
³⁵ Department of Gastroenterology, Hamar Hospital, Hamar, Norway.
³⁶ Department of Gastroenterology, Elverum Hospital, Elverum, Norway.
³⁷ Department of Gastroenterology, Bodø Hospital, Bodø, Norway.
³⁸ Department of Rheumatology, Betanien Hospital, Skien, Norway.
³⁹ Patient representative, Norges Psoriasis- og eksemforbund, Trondheim, Norway.
⁴⁰ Patient representative, Landsforeningen for fordøyelsessykdommer, Oslo, Norway.
⁴¹ Patient representative, Norsk Revmatikerforbund, Oslo, Norway.
⁴² Institute of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

Abstract

Background and objectives: The 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures.

Methods: Patients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis.

Results: Baseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases.

Conclusion: The NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.

Trial registration: ClinicalTrials.gov NCT02148640.

Keywords: biosimilar; chronic inflammatory disease; drug costs; health economics; infliximab; switching.

Publication types

Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Monoclonal / adverse effects
Antibodies, Monoclonal / therapeutic use*
Arthritis / drug therapy*
Colitis, Ulcerative / drug therapy*
Double-Blind Method
Drug Substitution
Female
Humans
Infliximab / therapeutic use*
Male
Middle Aged
Norway
Psoriasis / drug therapy*
Time Factors
Treatment Outcome

Substances

Antibodies, Monoclonal
CT-P13
Infliximab

Associated data

ClinicalTrials.gov/NCT02148640
EudraCT/2014‐002056‐40