Predicting drug-free remission in rheumatoid arthritis
Identifying predictors to reduce drug prescription in rheumatoid arthritis – a case study by Dr Ken Baker
The Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study formed the basis of an NIHR Newcastle BRC PhD Fellowship. In this study, patients with rheumatoid arthritis (RA) in remission were invited to stop their arthritis drugs and were monitored for 6 months. 23/44 patients experienced an arthritis flare, which could be accurately predicted by a 5-variable composite biomarker score. Data and samples from BioRRA have supported:
- a patent application by Newcastle University
- an industrial collaboration with an international pharmaceutical company
- two original research articles
- two further research projects
- two PhD Studentships
- one NIHR Clinical Lectureship
Progress into other NIHR funding streams
The NIHR Newcastle BRC supported my salary and tuition fee payments throughout my PhD studies. This allowed me to successfully complete my PhD, and subsequently be awarded an NIHR Clinical Lectureship to further develop my research career.
Successful collaboration between BRCs and industry
Following completion of the BioRRA study, I successfully negotiated with a major international pharmaceutical company to collaborate on analysis of BioRRA study plasma samples. This has allowed me to access high-sensitivity cytokine/chemokine assays not available to me within the University, and use this data to further analyse the changes in circulating cytokines at the point of arthritis flare (which will ultimately lead to further publication(s))
Creation or exploitation of intellectual assets
The BioRRA composite biomarker score forms the basis of a patent application by Newcastle University (“Predictors of Drug-Free Remission in Rheumatoid Arthritis”; International Patent Application Number PCT/GB2019/050902). If these biomarkers are successfully validated in an external cohort (a focus of my ongoing research), then they hold promise to be developed towards a future commercial assay to guide arthritis drug tapering and cessation in the clinic.
Facilitating and accelerating progress along the translational pathway
Data and biological samples from the BioRRA study have directly supported the following research activity:
- Biological Factors that Limit Sustained Remission in Rheumatoid Arthritis (BIO-FLARE) study – MRC Experimental Challenge Grant (£3.5 million)
- Understanding Remission and Flare in Rheumatoid Arthritis – JGW Patterson Foundation PhD Studentship (£134,000)
- Cellular Markers of Relapse in Rheumatoid Arthritis (CeMaRRA) study – British Society of Rheumatology Research Fellowship (£37,000)
- Somatic mutations in RA: NIHR Newcastle BRC PhD Studentship
Supporting the training and development of the research workforce
The BRC has provided frequent training opportunities on topics such as research governance, clinical trial design and grant application which were invaluable in helping me develop these essential and transferable research skills. The BRC also nominated me to attend the NIHR Infrastructure Doctoral Research Training Camp in both 2015 & 2017; at the latter of which I was awarded first place poster prize. My career development has been further augmented by external research prizes arising from BioRRA, including:
- 2019 Royal College of Physicians Turner-Warwick Lecturer (Northern Region)
- 2019 Association of North of England Physicians Dewar Research Worker’s Prize
- 2018 European League Against Rheumatism (EULAR) Abstract Award in Clinical Science
- 2017 First place clinical presentation prize. 23rd Annual Northern and Yorkshire Rheumatology Meeting
The primary focus of BioRRA was to identify potential biomarkers of drug-free remission in RA. Having achieved this, ongoing research (JGW Patterson PhD Studentship, for which I am the PI) aims to validate these biomarkers in an external cohort and develop a clinical assay. If successful, this ongoing work will lay the foundations for translation of these biomarkers to clinical practice potentially within the next 5-10 years, helping clinicians and patients decide when it is appropriate to taper or stop arthritis medication.
Furthermore, the unique design of BioRRA also permits analysis of longitudinal changes in immune parameters associated with arthritis flare versus remission. My ongoing research in this area aims to characterise the phenotype and function of circulating leukocytes associated with arthritis flare using high-dimensional techniques such as mass cytometry and single-cell sequencing. This work promises to yield insights in to the underlying immunopathology of arthritis flare, and may highlight potential novel therapeutic avenues with which to treat and prevent flare.
I am currently awaiting a decision on my application to the Academy of Medical Sciences Starter Grant for Clinical Lecturers Scheme. If successful, this grant would provide an additional £30,000 of consumable funding over the next 2 years, allowing me to generate further research publications as well as provide pilot data to support an NIHR Advanced Fellowship application. Ultimately, I aim to be an international leader in rheumatology research, leading a team of clinical and laboratory researchers to deliver a programme of translational research for patient benefit.