Infliximab is a chimeric IgG1 antibody approved for treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis. Across all these indications, infliximab and other tumour necrosis factor (TNF) inhibitors have substantially improved disease management.1 However, access to TNF inhibitors varies and is inversely related to socioeconomic conditions in each country.2 The patent for the infliximab originator (Remicade; Janssen Biologics, The Netherlands) expired in 2015 in Europe and in many other parts of the world.
The biosimilar infliximab CT-P13 was approved by the European Medicines Agency in 2013 and by the US Food and Drug Administration in 2016.
Randomised controlled trials in patients who have not previously received TNF inhibitors, comparing infliximab originator with CT-P13, have been done in ankylosing spondylitis (PLANETAS,3 a phase 1 study) and rheumatoid arthritis (PLANETRA,4 a phase 3 study). However, according to guidance for regulatory approval of biosimilars, CT-P13 has been approved for all six relevant indications.5, 6, 7 This extrapolation of indication has been debated in clinical communities, especially gastroenterology,8, 9 because the mechanisms of action for infliximab might differ between indications.10, 11 Several other TNF inhibitor biosimilars have been approved or are under regulatory review and will be available for therapeutic use in the coming years.6, 12
In Norway, an annual tender system for TNF inhibitors and related biological drugs was established in 2007. Cost calculations and impact on health-care budgets are key factors for drug selection. In 2014, CT-P13 was recommended by Norwegian Health Authorities for patients starting treatment with infliximab. The cost saving for CT-P13 was 39% in 2014 compared with originator infliximab, and increased to 69% after the 2015 tender. Thus, the introduction of biosimilar drugs could reduce financial burdens on health-care budgets. Additionally, biosimilars could improve overall and earlier access to these drugs in many countries with prescription restrictions based on their high cost.
Research in context
Evidence before this study
Patients starting biological treatment can receive biosimilar CT-P13 in many countries. However, switching of stable patients who are doing well on originator infliximab is controversial. Follow-up data from the PLANETAS and PLANETRA studies, as well as observational data, suggest that switching from originator infliximab to CT-P13 is safe and does not reduce effectiveness of treatment, but independent and randomised studies have been lacking. We searched PubMed and the abstracts of major conferences using the terms “biosimilar”, “infliximab”, “switch”, and either “IBD” or one of the individual diseases (“Crohns disease”, psoriasis” etc) on Oct 23, 2016, with no constraints on the timeframe for the search and no language restrictions. We identified no published, randomised, switch studies on infliximab.
Added value of this study
NOR-SWITCH addresses the important issue of switching from originator to biosimilar infliximab in stable patients, and is the first government-funded randomised study to do so. The study examined patients in all six relevant disease groups, using disease worsening as the common primary outcome.
Implications of all the available evidence
The NOR-SWITCH trial showed that switching from originator infliximab to CT-P13 was not inferior to continued treatment with the originator drug according to a prespecified non-inferiority margin of 15%. Thus, the findings suggest that patients can be switched from originator infliximab to biosimilar infliximab CT-P13. The study findings could substantially affect the use of CT-P13 and health budgets in many countries. However, caution is recommended in generalising these findings to other biological agents.
Cost savings are even more relevant if patients on stable treatment with an originator drug could safely be switched to the biosimilar. Concerns have been raised with regard to efficacy, safety, and formation of anti-drug antibodies (ADAbs) when switching to a biosimilar in patients who are doing well on a stable treatment with an originator drug.13, 14 To date, switch data from infliximab originator to infliximab biosimilar have been available only from open cohort studies15, 16, 17, 18 and from the second year extensions of the PLANETAS and PLANETRA studies.19, 20
The Norwegian Government granted 20 million NOK (€2·2 million) in the 2014 governmental budget for a study to examine whether switching from the originator to the biosimilar is safe. The NOR-SWITCH study was designed as a randomised controlled trial encompassing all six relevant diagnoses for which infliximab is currently approved to assess if CT-P13 was non-inferior to infliximab originator regarding efficacy, safety, and immunogenicity in patients who had been on stable infliximab originator treatment for at least 6 months.