The NOR-SWITCH study showed comparable safety, efficacy, and immunogenicity for patients with inflammatory bowel disease (IBD) who switched from reference infliximab to Celltrion biosimilar (CT-P13).
As the debate on the safety of switching between biosimilars and reference products continues to rage, a new study found that switching between reference infliximab (Remicade) and biosimilar CT-P13 (Inflectra, Remsima; Celltrion) in patients with inflammatory bowel disease (IBD) was safe and efficacious.
CT-P13 was approved in the United States as Inflectra in 2017 and was approved in the European Union under the name Remsima in 2013. Infliximab (IFX) is used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis, and IBD, an umbrella term for ulcerative colitis (UC) and Crohn disease (CD).
Previously, there were growing concerns over whether monoclonal antibodies such as IFX would interact differently in patients with IBD versus other rheumatic diseases, according to the authors of the study.
“It has been suggested that the clinically relevant mechanisms of action of infliximab might differ in different diseases, and there were some concerns in the gastroenterology community when biosimilar infliximab became available for use in clinical practice,” wrote the authors.
Details on the Study
The randomized, controlled, double-blind, comparative NOR-SWITCH study had a 52-week component, where patients were randomized 1:1 to receive CT-P13 or continue receiving Remicade, and a 26-week extension component, where all patients would receive CT-P13.
The study took place between October 2014 and July 2016. Of the 248 patients who enrolled in the study, 230 patients completed the 52-week main trial and 207 (90%) continued into the 26-week open extension trial.
Treatment emergent adverse events were similar among treatment arms, across disease groups, and in both components of the NOR-SWITCH trial. No deaths occurred.
Although nocebo effects were avoided on a group level in the main study due to the double-blind trial design, which prevented patients from knowing whether they received drug or placebo, investigators said they expect nocebo to be observed in the extension study as a result of its open study design.
The Main Trial
The main study included 155 patients with CD and 93 patients with UC; 123 patients switched from IFX to CT-P13 and 125 continued to receive IFX.
In the main study, 36.5% patients with CD from the group who switched to CT-P13 experienced disease worsening, as did 21.2% from the group that continued to receive IFX (95% CI, adjusted risk difference [ARD] −14.3%, −29.3 to 0.7).
A total of 46 disease worsening effects were recorded, with some patients experiencing more than 1 event.
In the patients who had UC, disease worsening occurred in 11.9% of patients in the CT-P13 group and 9.1% of patients in the IFX group (95% CI, ARD 2.6%, −15.2 to 10.0).
Clinical remission was present in 65% and 70% of patients with CD in the CT-P13 group and the IFX group, respectively; and in 93% and 88% of patients with UC.
Antidrug antibodies were detected in 5% of patients with CD and 17% of patients with UC in the CT-P13 group. They were also found in 4% of patients with CD and 11% of patients with UC in the IFX group.
The Extension Trial
The extension trial included 127 patients with CD and 80 patients with UC. For the maintenance group that continued to receive CT-P13, there were 65 (61%) patients with CD and 42 (39%) patients with UC. For the group that would switch from IFX to CT-P13, there were 62 (62%) patients with CD and 38 (38%) patients with UC.
In the extension trial 20.6% of patients with CD in the maintenance group and 13.1% of patients with CD in the IFX/CT-P13 switch group experienced disease worsening (95% CI, ARD 7.9%, −5.2 to 21).
Additionally, 15.4% of patients with UC in the maintenance group and 2.9% of patients with UC in the IFX/CT-P13 switch group experienced disease worsening (95% CI, ARD 12.4%, −0.1 to 25).
At the end of the extension study, investigators said, 65% and 75% of patients with CD achieved clinical remission in the maintenance group and IFX/CT-P13 groups, respectively. For patients with UC, 82% from the maintenance group and 86% from the IFX/CT-P13 group achieved clinical remission.
Antidrug antibodies were not observed in any patients with CD in the maintenance group. They were found in 1.6% of patients with CD in the IFX/CT-P13 group as well as 2.4% and 2.6% of patients with UC in the maintenance and IFX/CT-P13 groups, respectively.
Jørgensen KK, Goll GL, Sexton J, et al. Efficacy and safety of CT-P13 in inflammatory bowel disease after switching from originator infliximab: exploratory analyses from the NOR-SWITCH main and extension trials. BioDrugs. September 23, 2020. doi:10.1007/s40259-020-00438-7