New trial investigates non-response to rheumatoid arthritis treatment

Thursday 28th April 2016

A trial to uncover why around 40 per cent of patients suffering from rheumatoid arthritis do not respond to otherwise highly effective current drug therapies is being conducted by the NIHR Leeds CRF in partnership with researchers at Barts Health NHS Trust.

Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders in the UK, with 26,000 new cases diagnosed each year. Genetically engineered medications, called biologics, have transformed the treatment of Rheumatoid Arthritis. However, the annual cost to the NHS for these types of drug is around £160 million.

Identifying those patients unlikely to respond to certain biologics would enable them to embark on a more suitable alternative, avoiding unnecessary exposure to potentially toxic drugs and saving the NHS up to £18 million each year.

The researchers postulate that patients’ responsiveness to treatment is linked to the type of cells in the tissue lining joints, known as synovial tissue; in particular that response to rituximab is associated with the presence of B cells – a type of white blood cell in the synovial tissue. The aim of the trial - called Stratification of Biologic Therapies for RA by Pathobiology (STRAP) –  is to see whether synovial tissue B-cell presence can be used as a biomarker to predict rituximab treatment efficacy.

Before the trial patients will have synovial tissue biopsies taken, which will be analysed to determine tissue characteristic including B cell presence. Patients will then be randomly assigned to one of three licensed biologic treatments. After 16 weeks, the patients will be assessed to see how well they have responded to the treatment, with patients that fail to respond, switched to the alternative treatment.

Patients being treated at NIHR Leeds CRF and at Barts Health NHS Trust will also undergo a MRI scan of their hand and wrist as part of a novel sub-study, to understand the imaging features associated with synovial tissue characteristics and thus see whether analysis of these scans could provide an alternative, less invasive, means of identifying features predictive of response to each biologic treatment.

Musculoskeletal Speciality Clinical Lead for the CRF and Leeds PI for the study, Professor Maya Buch, said:

“This is one of two trials we are currently collaborating on with the CI, Prof. Pitzalis at Barts, in which we use synovial tissue biopsy based diagnostic to stratify patients with rheumatoid arthritis. We also hope this trial will enable us to assess the effectiveness of MRI for understanding how changes in joint tissue characteristics relate to features on MRI – so that MRI might offer an additional approach to stratify patients towards prediction of response to these biologic therapies.”

The trial, funded through the Medical Research Council and Arthritis UK, aims to recruit 207 patients and is expected to take three years to complete.