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Prevention of disease and the complications of treatment

Treating patients with rheumatoid arthritis (RA) costs the health service an estimated £560m per annum.

Pharmacogenetics can identify genetic variants that predispose individuals to serious adverse events


At the NIHR Manchester Musculoskeletal BRU we aim to investigate and test strategies for preventing RA and complications arising from therapies used in its treatment, to achieve both benefits to patients and reduce the healthcare burden.


The possibility that inflammatory arthritis may be preventable is a novel concept in rheumatology. However, due to key discoveries during the last five years, this proposal could now be tested for RA.

Screening to identify individuals at high risk of developing RA


Currently population screening is being used in research projects in Europe to identify rheumatoid factor (RF) and anti-citrillunated peptide antibodies (ACPA) positive individuals who, at the first sign of arthralgia, can be entered into a randomised double blind trial of rituximab, which is an biologic therapy targeting B-cells for depletion, to see if the number of individuals going on to develop RA can be reduced.

What we aim to achieve:

We propose to develop a more targeted screening strategy based on sophisticated risk profiling. We will establish a register of high risk individuals suitable for an intervention study, using the less expensive and widely used medications, hydroxychloroquinine, statins and vitamin D. Establishment of this register will also provide a unique opportunity to obtain samples from individuals in the earliest, pre-symptomatic phase of RA, which will be key in helping us understand the disease process. We envisage that our research will shed new insights into RA pathogensises and may ultimately inform development of further novel strategies for the prevention of RA.

Prevention of side effects of treatment with effective drugs


The use of methotrexate (MTX), a frequently used and effective medication for RA can in a very small number of cases (0.3% of patients treated) result in a rare but serious adverse event of pneumonitis (inflammation of the lung tissue).

What we aim to achieve:

Pharmacogenetics can identify genetic variants that predispose individuals to serious adverse events and is already adopted into rheumatology practice for screening. We will use proven strategies to identify genetic risk factors for the development of pneumonitis in RA patients treated with MTX. This screening test would bring considerable patient and healthcare economic benefit.


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