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Optimising anti-TNF treatment using biosimilars

Clinical Practice

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Last updated:10th Nov 2020
Published:7th Aug 2020

Biosimilars in Clinical Practice - What are Biosimilars?

Biological medicines have revolutionised healthcare since their development in the 1980’s. Recently, biosimilars have established their place in the clinic, benefitting almost every stakeholder in the healthcare system. So what are biosimilars and how could they be important to your practice?1

A biosimilar is a medicine containing a version of the active substance of an already-approved biological medicine whose patent has expired (known as a reference product); a biosimilar is approved once it has been shown not to have any clinically meaningful differences in terms of quality, safety and efficacy from the reference product.2–5

As of January 2020, 70 biosimilars have been approved by the EMA and 26 by the US FDA.6,7 Biosimilars based on anti-TNF products such as adalimumab, etanercept, infliximab, and rituximab have been approved for the treatment of gastroenterology, rheumatic, and dermatological diseases. Anti-TNF biosimilars, reduce costs by offering a lower-cost treatment option and can potentially improve patient outcomes by providing more treatment options.8 The arrival of biosimilars has led to cost reductions that allow earlier access to effective treatments, leading to improved patient outcomes and QoL.8 For example, the development of biosimilars to TNF inhibitors such as etanercept and adalimumab for the treatment of psoriasis has led to significant improvements in health-related quality of life in patients.9


Figure 1, Biological molecules have more complex structures than small molecule medicines.10 

Biosimilars are more costly and difficult to produce than generic versions of small-molecule drugs. It can take 5–10 years and an investment of $100–250 million to bring a biosimilar to market, compared with about 2 years and $1–10 million to develop a conventional generic.4

The manufacturer of an original biological medicine must demonstrate its safety and efficacy in clinical trials, in contrast, biosimilar development focuses on in-depth analyses to confirm that the biosimilar is highly similar to its reference product in terms of structure, composition, and in vitro activity.11 At least one clinical study is required to compare the pharmacokinetics of the reference product and biosimilar, and at least one randomised trial is required to demonstrate clinical equivalence.11 If a biosimilar has comparable safety and efficacy in one therapeutic indication to a reference product, then the data may be extrapolated to other indications already approved for the reference medicine.11,12 Consequently, a biosimilar may be approved in all indications for which the reference product has been approved without multiple clinical trials.11 Safety data are monitored and reported on a continuous basis according to rigorous pharmacovigilance regulations outlined by the EMA and US FDA.12,13

Interchangeability is a legal designation, which only exists in the US that indicates patients can expect the same outcome in terms of safety and efficacy with either a biosimilar or its reference product.12 In the EU, interchangeability is a scientific term meaning that a product can be safely switched.14 In the US it is a legal term which allows automatic substitution at the pharmacy level.14 This is slightly different to the term 'switching', which refers to the treatment decision made by a physician to switch patients treated with a reference product to a biosimilar. Substitution refers to a pharmacist substituting one prescribed reference product for a biosimilar without the need to consult a physician.15


Figure 2, Drug development comparison. The development processes for biologics and biosimilars are considerably more rigorous than the development process for small molecule generics.16

It is estimated that in the UK the healthcare system can make substantial savings of £200 million to £300 million per year if patients are initiated on or switched to biosimilars.3 These savings can then be reinvested into other aspects of patient care to increase the number of health service staff, to increase funding for nurses and to maintain the quality of the social care system.17 As the number of treatment options increases, manufacturers reduce the prices of their products to increase market share and this in turn increases patient access to biologic medicines.18,19


Figure 3, Estimated cost savings by biologic class over a ten-year period from 2017 to 2026.20

The Health Economic Perspective

Biosimilars provide enormous benefits from a health economics perspective.21 But how do anti-TNF biosimilars in particular offer a great value proposition across gastroenterology, rheumatology and dermatology diseases?

Inflammatory bowel diseases including Crohn's disease and ulcerative colitis are chronic inflammatory disorders. In the UK, the incidence rates are currently estimated to be 150 per 100, 000 person-years for Crohn's disease and 10 per 100 000 person-years for ulcerative colitis.22,23

Increasing confidence in the safety profiles of biosimilars such as infliximab and adalimumab is leading to a shift in practice toward early implementation and treatment with biosimilars of patients at risk of early disease progression.24

The introduction of biosimilars for infliximab, for example, is expected to have a major impact on the cost profile of gastroenterology disease. A Dutch study reported that cost savings over 5 years could yield €493 million in total, predominantly determined by price reduction of anti-TNF therapy with physicians switching patients towards biosimilars.25

There are a high number of comorbidities linked to inflammatory conditions such as osteoporosis, cardiovascular disease, neuropsychological disorders and metabolic syndrome. Biosimilars offer patients greater access to treatment at an earlier stage which may prevent the emergence of comorbidities.26

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How can biosimilars be used in patients and what is the evidence to support their use?

It is widely acknowledged that provider education and acceptance of biosimilars is one of the factors critical to increasing uptake of biosimilars.37 Recently the concept of the nocebo effect has gained renewed interest as a result of introducing biosimilars in therapy; gaps in patients’ and HCPs’ awareness, understanding, and perception of biosimilars may contribute to the nocebo effect, reducing the clinical benefit of biosimilars.37 Apart from the contribution of particular psychological factors to nocebo effects (e.g., general drug sensitivity, negative drug effects in the past, anxiety, etc.), the neurobiological predictors of nocebo responses are not well understood.38 In some cases, patients have discontinued biosimilars, despite having no worsening of disease, after switching from reference products.37 

Given the crucial contribution of the nocebo effect on clinical outcomes it is important that HCPs understand the scientific evidence behind biosimilar development and the biosimilar regulatory approval pathway.38 It is thought that when HCPs are confident in their biosimilar knowledge, they can help reduce the risk of nocebo effects and improve patient adherence.39

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References - Biosimilars in Clinical Practice

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