Rheumatoid arthritis (RA) affects around 1 in 100 adults, causing joint pain, stiffness and fatigue, and is estimated to cost the UK economy £2.5 billion each year.

Treatment often relies on powerful drugs that suppress the immune system, which can increase the risk of serious side effects such as infection. Supported by patient research partners and colleagues at the Universities of Birmingham, Glasgow and Oxford, researchers at the NIHR Biomedical Research Centre (BRC): Newcastle set out to understand whether some patients could safely reduce their medication once their arthritis was well controlled.

Together with the NIHR Clinical Research Facility: Newcastle, in two clinical trials 160 people were invited to stop their arthritis drugs. The studies found that around half of participants could stop their arthritis medication without experiencing a flare, and that this could be predicted using novel blood tests. These findings led to the development of a new NHS drug-tapering service in Newcastle and are now informing further work to develop a clinical test that could help guide drug tapering in the future.

Tapering treatment

Through an MRes project supported by the NIHR BRC:Newcastle, Dr Ken Baker led qualitative patient interviews which showed that many participants saw reducing treatment as an opportunity to regain a more normal lifestyle. These insights were later cited in Australian clinical management guidelines.

Continuing this work through an NIHR BRC: Newcastle PhD studentship and with support from the Wellcome Trust, Dr Baker led the BioRRA study following 44 patients with rheumatoid arthritis in remission and found that half were able to stop their arthritis medication and remain in drug-free remission for six months.

These findings led to the £2.3 million BIO-FLARE study, involving 121 patients across Newcastle, Birmingham, Glasgow and Oxford. Once again, around half of participants maintained drug-free remission for six months. Using longitudinal samples collected through these studies of blood, urine, stool and joint biopsies, researchers identified that particularly inflammatory proteins and epigenetic markers in blood could help predict which patients are most likely to taper their medication successfully.

Benefits for patients and the NHS

The findings have influenced clinical practice. Newcastle Hospitals NHS Foundation Trust has established the ROADMAP service, giving patients the opportunity to taper their arthritis medication under close supervision as part of routine NHS care while contributing to ongoing research.

Results from the first 37 patients show that 10 achieved drug-free remission for a median of 336 days. For patients taking biological or targeted therapies, this has generated drug cost savings of £4,934 per patient per year, while also reducing exposure to medications. The ROADMAP service forms part of Dr Baker's NIHR Advanced Fellowship, which is exploring how new techniques to predicting and detecting flare can support patients to make shared-care decisions on drug tapering.

Putting patients at the centre of research

Patient perspectives helped establish drug tapering as a research priority, informed the design of the clinical trials and continue to shape ongoing studies. Patient research partners, local patient groups and arthritis charities remain integral collaborators, helping to ensure the research addresses issues that matter most to people living with rheumatoid arthritis and maximising the impact of findings beyond academic and clinical settings.

Building towards personalised drug tapering

Researchers are preparing a funding application for a biomarker-driven multi-centre clinical trial of drug tapering in rheumatoid arthritis. In collaboration with other academic rheumatology centres across the UK, the team will test the clinical efficacy of our validated biomarkers to guide drug-tapering by providing an individualised risk stratification for arthritis flare. If successful, this would be the first personalised drug tapering approach in an immune-mediated inflammatory disease.

Guided by insights from Dr Baker’s NIHR Advanced Fellowship and working alongside industrial partners, the team also plans to develop these biomarkers into a clinical assay that could be used routinely within the NHS, supporting more personalised treatment, improved quality of life for patients and efficiency savings for healthcare services.