Biosimilar infliximab was launched in the UK in March 2015. Researchers from the National Health Service (NHS) Foundation Trust and King’s College London, discuss the trials that led to the approval of biosimilar infliximab [1].
The phase III PLANETRA trial included 606 adult patients with rheumatoid arthritis who were naïve to biologicals and not responding to methotrexate alone. The primary endpoint was an ACR20 (20% improvement in American College of Rheumatology core set measurements) response at 30 weeks. The 95% confidence interval (CI) for the biosimilar (Inflectra/Remsima; CT-P13) compared to Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) was -4% to +12%, achieving the equivalence standard of within the -15 to +15 range.
Safety findings reported over the 30 weeks showed no apparent imbalance between the biosimilar and the reference product (Remicade). Documentation submitted to the European Medicines Agency (EMA) reported serious adverse events at 54 weeks in 14% of the CT-P13 arm compared to 10% for Remicade. No differences in anti-drug antibody (ADA) levels were seen between the two arms at any time point.
A phase I infliximab trial (PLANETAS) for Inflectra/Remsima (CT-P13) was also carried out. This trial was carried out in 250 biologically naïve axial spondyloarthritis patients. The study was not powered as an equivalence study and therefore 95% CIs were not presented. However, it did find comparable pharmacokinetic and clinical responses between the two infliximab products. There was no imbalance in safety findings at 30 weeks and ADAs were comparable for CT-P13 and Remicade.
Open label extensions of both the PLANETAS and PLANETRA trials were also carried out to demonstrate the efficacy and safety of CT-P13 up to two years after first administration. The studies also showed that switching from Remicade to biosimilar infliximab did not appear to affect the safety or efficacy of treatment [2].
One notable difference between the two studies is the much lower rate of ADAs observed in the PLANETAS study compared to the PLANETRA study. The higher rate of ADAs in the PLANETRA study could be due to improved assay sensitivity, but may also reflect differences between rheumatoid arthritis and axial spondyloarthritis in terms of immunogenicity risk.
Conflict of interest
The authors of the research paper [1] declared that there were no conflicts of interest.
Editor’s comment
Readers interested to learn more about the PLANETRA and PLANETAS studies are invited to visit www.gabi-journal.net to view the following manuscript published in GaBI Journal:
Switching from the infliximab reference product to CT-P13 in patients with rheumatoid arthritis or ankylosing spondylitis: results of the PLANETAS and PLANETRA extension studies
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References
1. Rutherford AI, Galloway JB. Biosimilars in rheumatology: out of the laboratory and into practice. Expert Rev Clin Immunol. 2016;12(7):697-9.
2. GaBI Online - Generics and Biosimilars Initiative. Open-label studies show similarity of biosimilar infliximab and Remicade [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2016 Nov 4]. Available from: www.gabionline.net/Biosimilars/Research/Open-label-studies-show-similarity-of-biosimilar-infliximab-and-Remicade
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