Lianne, you did the research, tell us about yourself…

Hello, my name is Lianne, I am an epidemiologist at the University of Manchester. For the past 12 years I have been a researcher working on the BSRBR-RA study. In addition, I also have a research interest in the effects of treatments and outcomes in children and young people with childhood arthritis (JIA). Using data from BSRBR-RA, I have recently published two pieces of research looking at how well patients with rheumatoid arthritis (RA) do after they start one of two related treatments for RA, an etanercept originator (the original) or an etanercept biosimilar.

What is the BSRBR-RA?

The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is an observational cohort study that started in 2001 collecting data from patients with RA starting biologic therapies (or JAK inhibitors). The aim is to answer questions such as; How well do they work? How safe are they?

What are etanercept ‘originators’ and ‘biosimilars’?

Etanercept is one of the main treatment options for patients with RA and we have been using it in rheumatology for over 20 years. In 2015, the patent for the original etanercept drug (the originator) expired in Europe and consequently other pharmaceutical companies were able to make the drug, often at a much lower cost. These new versions of the drug are known as biosimilars. To be approved, biosimilar therapies must demonstrate that they work as well as originators in clinical trials, and as this is assumed to be true, the NHS set guidelines for at least 90% of patients who would have been treated with the originator version to instead be prescribed the biosimilar product by 2019.

If I am starting biologic treatment for the first time, does it make a difference whether I start etanercept originator or etanercept biosimilar?

In my first publication, I looked at 1806 adults with RA from the BSRBR-RA study starting either etanercept originator or etanercept biosimilar for the first time in routine clinical practice in the UK. In the 1009 starting etanercept originator and the 797 starting etanercept biosimilar, 30% achieved remission after one year of treatment, with no difference found between the two treatments. Most patients (three out of four) on either treatment (originator and biosimilar) were still receiving their treatment after one year, with again no difference between the groups, another indication that the biosimilar works as well as the originator.

What about those patients who were already receiving etanercept originator and were then switched to the biosimilar?

As biosimilars are often much cheaper than originators, the NHS mandate for 90% of patients who require etanercept to receive the biosimilar also applied to patients already receiving the originator, as the cost saving to the NHS would be substantial. However, when biosimilars were first introduced, most data on their effects were limited to patients who were starting a new biologic therapy rather than switching from an existing therapy. The idea of changing a drug which had been so effective for so many patients caused some concern among patients. It was difficult to speak beyond the hypothetical at the time as there was so little data about what would happen if patients switched products.

In my second publication, I identified 1024 adults with RA from the BSRBR-RA changing from the etanercept originator (the original) to an etanercept biosimilar. I wanted to see how well they did after switching but needed a comparison group to see what ‘might’ have happened had they remained on the originator. Therefore, each patient was matched to a patient who remained on the originator (with similar characteristics such as age, gender, and how long they had had arthritis for).

Those who swapped onto the biosimilar were just as likely to remain on their treatment (an indication that it is working for them without causing side effects severe enough to have to stop) compared with those who continued the originator. Two-in-three of all patients in both groups were still on therapy after three years, indicating that both treatments (originator or biosimilar) were controlling their arthritis. In addition, after one year of treatment, patients did equally well regarding ongoing control of their arthritis, in terms of symptoms, such as the number of swollen joints, regardless of whether they switched or not.

Can you summarise?

These two analyses are the largest analyses of adults with RA comparing etanercept originator with etanercept biosimilar in (1) patients newly starting treatment, and (2) patients who are switched from originator to biosimilar. Using these real-world data, we have shown that in both cases, the patients’ arthritis (disease activity) was similar between treatments, and patients remained on treatment for a similar amount of time.

What does this mean for patients?

This is reassuring to patients and the clinical team when either a patient with RA needs to start an etanercept therapy as their first biologic (either originator or biosimilar), or have been advised to swap treatment from the etanercept originator to the biosimilar therapy, as the two products do appear to be very similar.

Has this research had any impact on clinical practice?

The BSRBR-RA study is not a clinical trial, it is an observational study where we look at what is happening with treatments for RA in the real world, over many years. This means that it takes a long time for the information coming into the study to impact the way that treatments are prescribed and managed in the rheumatology community. We are working with the British Society for Rheumatology (BSR) and the charity NRAS (National Rheumatoid Arthritis Society) to ensure that our research findings are visible and are incorporated into future patient information sheets and guidelines. Sharing the information that has shown how similar these drugs are and that the switching appears to be safe and effective is important, to ensure patients are well informed about their treatments.

Looking to the future – are you planning any further work on this?

This data on etanercept biosimilars is very reassuring but we will continue to collect and analyse data on this, and other biologic drugs (originators and biosimilars), on how well they work, and to ensure that they are similar in their side effect profiles.

In addition, whilst most of the other anti-TNF biosimilars have been trialled in patients with RA, they are often not tested in children and young people with childhood arthritis (JIA), rather just ‘assumed’ to be the same as the originator and licensed for JIA accordingly. Alongside the BSRBR-RA, we also host a large register of children with JIA (UK JIA Biologics Register). We are currently undertaking an analysis of outcomes in children who have switched to biosimilars and hope to publish these data soon.

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