The use of biosimilars has truly taken off in the past few years and is expected to increase further. Recent findings add to the increasing real-world evidence that switching from originator to biosimilar biological disease-modifying antirheumatic drugs (bDMARDs) is safe and efficacious.
Professor Kvien (University of Oslo and Diakonhjemmet Hospital, Oslo, Norway) presented an update on biosimilars, which focused on switching from originator to biosimilar. First, he shortly discussed approval issues, stating that regulatory agencies in Europe and the United States have set up strict guidelines for the approval of biosimilars, which include extensive pre-clinical examinations. However, for biosimilars, less clinical data are required than for an originator product. In general, biosimilars will be considered on the same level as originator products in extrapolated indications when treatment is started or changed for medical reasons by most rheumatologists.
A different matter is replacing an originator product with a biosimilar when (substantial) cost savings are involved. From the various studies on switching, Kvien highlighted the NOR-SWITCH trial. This randomized, non-inferiority, double-blind, Phase 4 trial with 52 weeks of follow-up trial was exclusively funded by the Norwegian government. It included 482 patients on stable treatment with the reference product infliximab across six different indications.
In total, 32% patients in the full analysis set had Crohn's disease, 19% had ulcerative colitis, 19% had spondyloarthritis, 16% had rheumatoid arthritis, 6% had psoriatic arthritis, and 7% had chronic plaque psoriasis. Patients were randomized to continued treatment with the reference product (n=241) or a switch to CT-P13 (n=241) in which the dosing regimen was unchanged. The primary endpoint was the occurrence of disease worsening, defined by the disease-specific composite measures or clinically significant worsening leading to a major change in treatment. It was shown that disease worsening occurred in 26% of patients in the infliximab originator group and in 30% of patients in the CT-P13 group (per-protocol set; adjusted treatment difference -4.4%, 95% CI: -12.7 to 3.9). The frequency of adverse events (AEs) was similar between groups, including serious AEs (10% for infliximab originator vs 9% for CT-P13).
No differences were observed between the two groups in secondary endpoints, which included time to study drug discontinuation, remission rates, C-reactive protein levels, anti-drug antibody formation, and drug trough levels. Thus, the NOR-SWITCH study demonstrated that switching to CT-P13 was not inferior to continued treatment with originator infliximab. Kvien added that these results support switching from originator product to CT-P13 for non-medical reasons. Although the extension study has not yet been published, Kvien told the audience that the results confirm those from the main trial. “Interestingly, there was less disease worsening in those who switched,” he added. Kvien ended his talk by stating that things are getting even more exciting as more and more new biosimilars are becoming available: “This is just the beginning.”(2)
1. Jørgensen KK et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomized, double-blind, non-inferiority trial. Lancet 2017;389:2304-2316.
2. Kvien TK. An update on biosimilars. SP0024. EULAR 2018.