What is it about?

What was already known? Biologic therapies have revolutionised treatment and outcomes for people with rheumatoid arthritis (RA). Over the years many different types of biologic therapies have become available (also known as different classes), each treating inflammation in different ways. The expanding choice of biologics allows patients to switch biologic if their current treatment is not working. For some patients, even after switching, their disease and symptoms may persist. The aims of this analysis were to see how many patients had what we defined as biologic refractory RA, defined as receiving at least three different classes of biologic drugs. This would give us more info on burden of disease, which can feel into health care delivery planning. We also aimed to see if we could identify early on who these patients were. What was discovered? The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) collects information on people with RA starting biologic therapy. It started recruiting patients starting anti-TNF drugs in 2001 and since then has continue to capture data on new types of biologics as they become available for patients with RA. Between 2001 and 2014, 13502 patients with RA started a biologic for the first time and consented to participate in the register. Over the duration of follow-up, 6% had used at least three different classes of biologics. As there are multiple drugs within each class, there were actually >1100 (~9%) patients who had tried at least 4 different biologic drugs. Almost 40% of patients did not respond to any drug and only 11% tried multiple drugs as they could not tolerate the various drugs, stopping for side effects. The rest had mixed reasons for stopping. Although there was no single characteristic which could predict this, patients who had worse symptoms (such as pain and fatigue) at the start of their first drug were more likely to try more different drugs. We also found that patients who smoke were more likely to have required multiple biologic drugs in an attempt to control their disease. Smoking has previously been associated with lesser responses to biologic drugs (Hyrich et al 2006). In more recent years we found that with more drug choices, patients are trying more drugs quicker, a sign that more drugs are available and doctors have more options of drugs to control disease.

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Why is it important?

This is the first observational study to evaluate the extent of biologic refractory RA. This is an important finding as it allows the rheumatology community and funders the opportunity to better design services with the knowledge of the numbers of patients who will require regular clinical review. As the choice of biologics and other related therapies increases, particularly with respect to new modes of action, it will be important for budget planning, to ensure that funding for these drugs are not rejected based solely on the number of biologics a patient has previously received. This information will also help with future treatment guideline development, such as the management of difficult to treat RA, currently the focus of a new EULAR task force.


After becoming aware that many of the patients within the BSRBR-RA have been exposed to multiple biologics, myself and the co-authors were interested to investigate the extent of this. I have enjoyed working on the analysis and also working alongside Dr. Buch and Dr. Isaacs on this project and have appreciated their imput from a clinic perspective. I am now interested to follow the work of the new EULAR task force who are aiming to define "difficult-to-treat" rheumatoid arthritis.

Dr. Lianne Kearsley-Fleet
University of Manchester

Read the Original

This page is a summary of: Biologic refractory disease in rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis, Annals of the Rheumatic Diseases, July 2018, BMJ, DOI: 10.1136/annrheumdis-2018-213378.
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