Biosimilar Proves to be OK for Switching


Clinical trial shows that switching from the infliximab originator to its biosimilar does not compromise safety or effectiveness of treatment.

Rheumatoid disease patients who are stable on the TNF antagonist infliximab can switch to its biosimilar, CT-P13, without compromising safety, a new study shows.

The 52-week trial, called NOR-SWITCH, found that switching from the biologic to its biosimilar did not lead to a more progressive disease state, compromise safety or increase immunogencity in 482 adult patients with rheumatoid disease. 

While follow-up and observational data have shown that switching is safe, this is the first randomized, non-inferiority, double-blind trial on switching stable patients from a biologic to a biosimilar. The findings address concerns that biosimilars may not be suitable for switching in stable patients.

The Norwegian study, by Kristin Jørgensen M.D., from Akershus University Hospital in Lorenskog, Norway, and colleagues, appears in the May 11 issue of The Lancet.

"Switching has been one of the most controversial issues related to the introduction of biosimilars. Studies such as Jørgensen and colleagues … are key to improving the acceptance of biosimilars by prescribing physicians, reimbursement decision makers and patients,” wrote Richard Veselý and Peter Richardson in an editorial that accompanied the study. “Although the study’s design does not allow for conclusions on individual diseases, its results support the idea that infliximab originator can be replaced during treatment with a biosimilar." 

CT-P13 was approved in the United States in 2016 by the U.S. Food and Drug Administration for Crohn's disease, ulcerative colitis, rheumatoid arthritis, active ankylosing spondylitis, active psoriatic arthritis and chronic severe plaque psoriasis. Prior to its approval, the biosimilar met all safety and efficacy requirements.

The Lancet study

Data for the phase four trial was collected from 40 Norwegian study centers. The final analysis included patients with Crohn’s disease (32%), ulcerative colitis (19%), spondyloarthritis (19%), rheumatoid arthritis (16%), psoriatic arthritis (6%) and chronic plaque psoriasis (7%).

Adult patients who were on stable treatment for at least six months with infliximab (Remicade, Jansen Biologics) were randomly assigned to either continue with the infliximab originator (241 patients) at the same dosing level or switch to CT-P13 (241 patients) at an equivalent dosing level.

The primary endpoint was disease worsening at 52-week follow-up, but the two groups were similar:  26% in the infliximab originator group and 30% in the CT-P13 group. The 95% CI of the adjusted treatment difference of –4·4% (–12·7 to 3·9) was within the predefined non-inferiority margin of 15%.

The frequency of adverse events was similar between groups (for serious adverse events, 24 [10%] for infliximab originator vs 21 [9%] for CT-P13; for overall adverse events, 168 [70%] vs 164 [68%]; and for adverse events leading to discontinuation, nine [4%] vs eight [3%], respectively).

Potential cost savings

Biosimilars offer a potential cost savings. For example, in Norway, estimates show that it could be between 39 and 69 percent of the cost of the originator product. Still, in the absence of clinical trials on switching, doctors have been reluctant to switch patients who are stable on biologics, regardless of potential cost savings.

The authors of the editorial say there are other issues with switching that have yet to be addressed, specifically, the clinical importance of differences in immunogenicity that have been seen in laboratory tests and extrapolation to pediatric indications.

In the United States, several other TNF inhibitor biosimilars have been approved or are under regulatory review for therapeutic use.

In the European Union, the first biosimilar was approved in 2006 and 28 new biosimilars have since been approved for various conditions. In 2013, the EU approved Remsima (Celltrion Healthcare), as a biosimilar to infliximab. It was the first biosimilar monoclonal antibody to be authorized in the EU. A patient registry has been established to monitor adverse events and long-term efficacy. Post-authorization studies have confirmed similarity and extrapolation, but to date, have not provided  new information on efficacy and safety.



This trial was supported by a direct grant from the Norwegian Government, by the Ministry of Health and Care Services.


Kristin K Jørgensen, Inge C Olsen, Guro L Goll, Merete Lorentzen, 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," The Lancet. Published Online May 11, 2017, S0140-6736(17)30068-5

Richard Veselý and Peter Richardson. "The switch to infliximab biosimilars," The Lancet. Published Online May 11, 2017, S0140-6736(17)31258-8


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