NIHR | Manchester Biomedical Research Centre

Rheumatoid arthritis – taking a step towards changing clinical practice in assessing disease activity

Professor Anne Barton

Author: Professor Anne Barton

Inflammation Cluster Lead / Rheumatic and Musculoskeletal Diseases Co-Theme Lead

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A key part of treating patients with joint inflammation effectively is, of course, to chart any changes in the activity of their disease. This enables clinicians, like me, to alter an individual’s medication to the right dose according to any improvements or deteriorations.  The aim is to ensure that a chronic disease, like rheumatoid arthritis (RA), remains tightly managed, with a priority being to control joint inflammation.

In rheumatology, the tool we use to measure disease activity in people with RA is called DAS28.  DAS stands for ‘disease activity score’ and the number 28 refers to the 28 joints that are examined in this assessment.

Four components are considered in DAS28: number of tender joints (out of 28 joints), number of swollen joints (out of 28 joints), blood markers of inflammation and patient-completed well-being assessment.

The results from these four areas are then fed into a complex mathematical formula to produce the overall disease activity score.  A patient’s disease activity rating is used to inform decisions about their medication type and dosage.

However, despite being routinely used in clinical practice, there are issues with DAS28. Whilst it provides an aggregated picture of a patient’s overall health in relation to RA, it is not the most accurate indicator of joint inflammation. Managing joint inflammation is a key aspect of RA treatment because, if it is not treated effectively with the right drugs, it can lead to joint damage and disability. So, it is critically important to control joint inflammation and the drugs we use were primarily developed to address this aspect of the disease.

Refining the disease activity score

Manchester BRC’s overall aim is to ensure that each patient gets the treatment that is right for them as an individual (precision medicine) and, for RA sufferers, we felt that a further refinement of DAS28, which focuses on joint inflammation, was the right way forward.

Myself, Dr Suzanne Verstappen and Dr Stephanie Ling, who worked on the investigation, wanted to test whether the imaging of joint inflammation would provide a standard against which an updated DAS for RA could be derived.

Working with our research colleagues at NIHR Leeds BRC, Edinburgh University and Queen Mary University of London, we used information from two separate studies (SERA and IACON) to compare each component of  DAS28, to see which correlated best with the amount of joint inflammation; the inflammation was assessed using ultrasound scanning.

Using the results of this comparison, we developed a 2 component disease activity score (2C-DAS28), focusing just on swollen joints and blood markers as the best indicators for joint inflammation.  A third, existing study (PEAC) was used to confirm that 2C-DAS28 showed better alignment with joint inflammation than the original DAS28.

Preventing joint damage – the key goal for rheumatologists

While this refined DAS tool was potentially significant, our team needed to prove that it would be accurate in predicting long term joint damage. Using data from a University of Manchester supported study (NOAR), which provided x-ray information, we were able to show that 2C-DAS28 was much better at predicting the development of erosions (joint damage) than the original DAS28.

This work, by twenty researchers from the three organisations, was published in the journal Rheumatology earlier this year.

Future benefits for patients

Current drugs for RA target joint inflammation so, in practical terms, this updated measure means that, in the future, doctors will be better able to identify ways of predicting which medication will be effective for different patients.  It will also help clinicians to match the right treatments to the right patients.

My view is that rheumatologists need to use a more refined DAS28 in assessing the effectiveness of drug treatment in patients with RA. We wouldn’t recommend replacing the conventional DAS28, as it provides useful information about the patient response to treatment as a whole (including how patients feel their disease is doing), but the 2C-DAS28 may be a better measure of whether the drug prescribed is actually working to control joint inflammation. Even the 2C-DAS28 is not a perfect measure. More research is needed to consolidate our findings, start to move clinical opinion towards a reassessment of DAS28’s accepted use in clinic and define even better measures that more closely reflect joint inflammation. However, this paper is an important step in providing further scientific evidence that focusing mostly on joint inflammation will yield the best results for our patients, when selecting drugs to control inflammation.

Professor Anne Barton