Era of biosimilars in rheumatology: reshaping the healthcare environment

Abstract

Compared with the original approved biological drug on which it is based, a biosimilar has highly similar physicochemical characteristics and biological activity, as well as equivalent efficacy and no clinically meaningful differences in safety and immunogenicity. Before they are approved, biosimilars must undergo a rigorous development process using state-of-the-art technologies to establish biosimilarity to the reference biological product. After approval, biosimilars must comply with good pharmacological practices for biological drugs. Several biosimilar disease-modifying antirheumatic drugs (bsDMARDs) based on the tumour necrosis factor inhibitors adalimumab, etanercept and infliximab have been approved for use in patients with rheumatic diseases. Substantial cost savings can be made if biological-naive patients begin treatment with bsDMARDs, and patients receiving original biological DMARDs (bDMARDs) are switched to bsDMARDs. Despite the consistently similar efficacy, safety and immunogenicity of bsDMARDs relative to their respective original bDMARDs, switching from a reference bDMARD to a bsDMARD can result in nocebo responses, such as subjective increase of disease activity and pain-related adverse events. This may have a negative impact on adherence to bsDMARDs in clinical trials and clinical practice. To ensure optimal and rational integration of bsDMARDs into rheumatology practice and realise the full cost-saving efficacy of these drugs, rheumatologists must be aware that careful communication of the cost-saving efficacy and safety of bsDMARDs to their patients is the key to a successful long-term switch to bsDMARD therapy.

Keywords: anti-tnf; arthritis; autoimmune diseases; dmards (biologic); rheumatoid arthritis.

Figure 1

Health economic impact of anti-TNF biosimilars in the EU and EU-5 countries in 2016. EU, European Union; TNF, tumour necrosis factor.

Figure 2

The stepwise approach to the development of reference and biosimilar products.

Figure 3

Comparison of TNF neutralisation activity of SB4 and etanercept reference product (40 lots of EU-sourced product and 40 lots of US-sourced product) measured using a TNF neutralisation assay that uses a luciferase reporter gene cell line containing an upstream NF-kB binding sequence. The dotted line indicatesthe similarity range (mean ± κSD) based on results of etanercept obtained from the EU. EU, European Union; TNF, tumour necrosis factor.

Figure 4

ACR20, ACR20 and ACR70 response rates (proportions of patients meeting ACR 20, 50% or 70% improvement criteria) in patients with rheumatoid arthritis randomised to receive double-blind SB5 (SB5 group) or reference adalimumab (ADL overall group) at week 0, and patients in the ADL group who were randomised at week 24 to continue double-blind ADL (ADL/ADL group) or switch to SB5 (ADL/SB5 group) up to week 52 in a phase III clinical trial. ACR, American College of Rheumatology; ADL, adalimumab.

Figure 5

Neuroimaging of a nocebo responder with activations of brain regions involved in anticipatory anxiety projected onto a 3D rendering model of the brain. Image courtesy of Fabrizio Benedetti. 3D, three dimensional.

Figure 6

Kaplan-Meier curve showing proportions of patients who continued to receive treatment with biosimilar infliximab (CT-P13) in the BIO-SWITCH study or biosimilar etanercept (SB4) in the BIO-SPAN study over 6 months. Shown is the survival curve with 95% CI (shaded areas).