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, 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

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.

Conflict of interest statement

GLG reports personal fees from AbbVie, Biogen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Orion Pharma, Celltrion and Boehringer Ingelheim. KKJ reports personal fees from Tillott, Intercept and Celltrion. NB reports personal fees received from Orion Pharma, Roche, Napp Pharmaceuticals, Pfizer and Takeda. ICO reports grants from 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. KST reports personal fees and nonfinancial support from AbbVie, Orion, Novartis, Janssen, Celgene, Mundipharma, Pfizer, MSD and Shire and nonfinancial support from CSL Behring. CM reports personal fees from Novartis Norge AS, LEO Pharma AS, ACO Hud Norge AS, Celgene AS, AbbVie and Galderma Nordic AB. JJ reports personal fees from MSD, AbbVie, Celltrion, Orion Pharma, Takeda, Napp Pharm, AstroPharma, Hikma and Pfizer. TKK reports grants from 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.

© 2019 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Figures

Figure 1
Figure 1
Patient disposition in the NOR‐SWITCH main and extension study.
Figure 2
Figure 2
Forest plot of risk difference according to disease. The figure shows data for the per‐protocol set. Risk difference is adjusted for treatment duration of infliximab originator at extension study baseline (week 52).
Figure 3
Figure 3
Change in disease‐specific composite measures during 78 weeks of follow‐up in the NOR‐SWITCH main and extension study in the per‐protocol set. (a) HBI for Crohn's disease. (b) PMS for UC. (c) Ankylosing Spondylitis Disease Activity Score for SpA. (d) Disease Activity Score in 28 joints with CRP for RA and PsA. (e) Clinical Disease Activity Index for RA and PsA. (f) Simplified Disease Activity Index for RA and PsA. (g) PASI for psoriasis. The coloured areas display the 95% confidence intervals from a mixed model adjusted for treatment duration of infliximab originator at main study baseline (week 0).

References

    1. Kuek A, Hazleman BL, Ostor AJ. Immune‐mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J 2007; 83: 251–60.
    1. Putrik P, Ramiro S, Kvien TK, Sokka T, Uhlig T, Boonen A. Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country's wealth? Ann Rheum Dis 2014; 73: 2010–21.
    1. Uhlig T, Goll GL. Reviewing the evidence for biosimilars: key insights, lessons learned and future horizons. Rheumatology 2017; 56: iv49–62.
    1. Yoo DH, Hrycaj P, Miranda P et al A randomised, double‐blind, parallel‐group study to demonstrate equivalence in efficacy and safety of CT‐P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013; 72: 1613–20.
    1. Park W, Hrycaj P, Jeka S et al A randomised, double‐blind, multicentre, parallel‐group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT‐P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013; 72: 1605–12.
    1. Emery P, Vencovsky J, Sylwestrzak A et al A phase III randomised, double‐blind, parallel‐group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 2017; 76: 51–7.
    1. Smolen JS, Choe JY, Prodanovic N et al Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double‐blind trial: clinical, structural and safety results. Rheumatology 2017; 56: 1771–9.
    1. Komaki Y, Yamada A, Komaki F, Micic D, Ido A, Sakuraba A. Systematic review with meta‐analysis: the efficacy and safety of CT‐P13, a biosimilar of anti‐tumour necrosis factor‐alpha agent (infliximab), in inflammatory bowel diseases. Aliment Pharmacol Ther 2017; 45: 1043–57.
    1. Park W, Yoo DH, Miranda P et al Efficacy and safety of switching from reference infliximab to CT‐P13 compared with maintenance of CT‐P13 in ankylosing spondylitis: 102‐week data from the PLANETAS extension study. Ann Rheum Dis 2017; 76: 346–54.
    1. Yoo DH, Prodanovic N, Jaworski J et al Efficacy and safety of CT‐P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT‐P13 and continuing CT‐P13 in the PLANETRA extension study. Ann Rheum Dis 2017; 76: 355–63.
    1. Emery P, Vencovsky J, Sylwestrzak A et al Long‐term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4. Ann Rheum Dis 2017; 10.1136/annrheumdis-2017-211591. [Epub ahead of print]
    1. Nikiphorou E, Kautiainen H, Hannonen P et al Clinical effectiveness of CT‐P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther 2015; 15: 1677–83.
    1. Kim YH, Pesegova M, Alexeeva O et al DOP061 Phase III randomised, double‐blind, controlled trial to compare biosimilar infliximab (CT‐P13) with innovator infliximab in patients with active Crohn's disease: early efficacy and safety results. J Crohn's Colitis 2017; 11(Supplement_1): S62.
    1. Jorgensen KK, Olsen IC, Goll GL et al Switching from originator infliximab to biosimilar CT‐P13 compared with maintained treatment with originator infliximab (NOR‐SWITCH): a 52‐week, randomised, double‐blind, non‐inferiority trial. Lancet 2017; 389: 2304–16.
    1. van Schie KA, Hart MH, de Groot ER et al The antibody response against human and chimeric anti‐TNF therapeutic antibodies primarily targets the TNF binding region. Ann Rheum Dis 2015; 74: 311–4.
    1. Schaeverbeke T, Truchetet ME, Kostine M, Barnetche T, Bannwarth B, Richez C. Immunogenicity of biologic agents in rheumatoid arthritis patients: lessons for clinical practice. Rheumatology 2016; 55: 210–20.
    1. Glintborg B, Sorensen IJ, Loft AG et al A nationwide non‐medical switch from originator infliximab to biosimilar CT‐P13 in 802 patients with inflammatory arthritis: 1‐year clinical outcomes from the DANBIO registry. Ann Rheum Dis 2017; 76: 1426–31.
    1. Boone NW, Liu L, Romberg‐Camps MJ et al The nocebo effect challenges the non‐medical infliximab switch in practice. Eur J Clin Pharmacol 2018; 74: 655–61.
    1. Tweehuysen L, van den Bemt BJF, van Ingen IL et al Subjective complaints as main reason for biosimilar discontinuation after open label transitioning from originator to biosimilar infliximab. Arthritis Rheumatol 2018; 70: 60–8.
    1. Glintborg B, Kringelbach T, Bolstad N et al Drug concentrations and anti‐drug antibodies during treatment with biosimilar infliximab (CT‐P13) in routine care. Scand J Rheumatol 2018; 47: 418–21.
    1. Razanskaite V, Bettey M, Downey L et al Biosimilar infliximab in inflammatory bowel disease: outcomes of a managed switching programme. J Crohn's Colitis 2017; 11: 690–6.
    1. Goll GL, Haavardsholm EA, Kvien TK. The confidence of rheumatologists about switching to biosimilars for their patients. Joint Bone Spine 2018; 85: 507–9.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere