Switching to biosimilar bDMARDs is safe and efficacious

The use of biosimilars has truly taken off in the past few years and is expected to increase further. Results have shown that switching to biosimilar CT-P13 is not inferior to continued treatment with originator infliximab. These findings add to the increasing real-world evidence that switching from originator to biosimilar biological disease-modifying antirheumatic drugs (bDMARDs) is safe and efficacious.

Regulatory agencies in Europe and the United States have set up strict guidelines for the approval of biosimilars, which include extensive pre-clinical examinations. These guidelines also permit abbreviated clinical development paths for biosimilars than for an originator product. In general, biosimilars will be considered on the same level as originator products when treatments are started or changed for medical reasons by most rheumatologists. On the contrary, replacing an originator product by a biosimilar is carried out on non-medical grounds for (substantial) cost-savings only.

There is evidence from various studies on switching, most notably from the NOR-SWITCH trial. This randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up was exclusively funded by the Norwegian government. It included 482 patients on stable treatment with the reference product infliximab across six different indications. In the full analysis set, 32% of patients had Crohn's disease (CD), 19% had ulcerative colitis (UC), 19% had spondyloarthritis (SpA), 16% had RA, 6% had psoriatic arthritis (PsA), and 7% had chronic plaque psoriasis (Ps). Patients were randomised to continued treatment with the reference product (n=241) or switch to CT-P13 (n=241) in which the dosing regimen was unchanged. Primary endpoint was occurrence of disease worsening, defined by the disease-specific composite measures, or clinically significant worsening leading to a major change in treatment.

Disease worsening occurred in 26% 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 -12.7-3.9). 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. These results support switching from originator product to CT-P13 for non-medical reasons.[6] Whereas the extension study has not yet been published, the results presented by Prof. Kvien (University of Oslo and Diakonhjemmet Hospital, Norway) confirm those from the main trial.[7]