Background

What is STRAP?
The STRAP Trial is an open label, randomised controlled clinical trial which aims to test the utility of synovial histopathology and B cell number together with specific molecular signatures as potential biomarkers to guide therapeutic decisions in patients failing DMARD therapy to improve on current response rates and identify patients more likely to respond. Patients will be randomised to receive Rituximab, Tocilizumab or anti-TNF therapy (etanercept) following a baseline synovial biopsy.

STRAP is an important clinical trial within MATURA (Maximising Therapeutic Utility in Rheumatoid Arthritis) which is an ambitious research project jointly funded by MRC and ARUK to identify and test biomarkers predictive of response to therapy in rheumatoid arthritis (RA), thereby allowing the stratification of patients into groups according to the therapies that are most likely to be effective. The project comprises two work-streams: Workstream 1 is managed by Prof Costantino Pitzalis at the Centre for Experimental Medicine and Rheumatology, and Workstream 2 is managed by Prof Anne Barton at the Centre of Excellence for Genetics and Genomics at the University of Manchester'.

Goals of STRAP

• To discover biomarkers that predict response to each of the three treatments; Rituximab, Tocilizumab and Etanercept.
  • We will do this by testing the existing evidence that different synovial pathotypes (the strata) are associated with diverse treatment response to these targeted biologic therapies.
  • At the same time, we aim to identify tissue biomarkers of response / resistance by investigating synovial biopsies emerging from STRAP.
• To test the hypothesis that Rituximab is inferior to the other two drugs (treated as a single comparison) in B cell poor patients.

 

 

Why is STRAP important?
Rheumatoid arthritis (RA) is a disease in which inflammation of joints can cause pain, stiffness, lasting damage and disability. It affects an estimated 500,000 people in the UK and has important impacts on their lives. For example, within 5 years of diseases onset, 33% people are unable to remain in full-time work.

There have been dramatic advances in treatment of RA in recent years with the introduction of new drugs and prompt treatment. However, at the moment, we have no means of predicting which patients will respond best to which drug and thus the drugs are prescribed on a 'trial and error' basis. However, we know that the longer it takes to find an effective therapy, the more joint damage accumulates and the worse the long-term outcome is for patients. By identifying predictors of response to drugs, patients with RA can be given the drug that they are most likely to respond to, as soon as they fail first-line therapy.  This will mean not only benefits to patients but potential cost benefits to the NHS and service providers.

What is the methodology for STRAP?
This trial is recruiting patients from multiple hospitals across the UK. Participants undergo a synovial biopsy of an affected joint before then being randomly allocated to one of the three treatments. How well everyone responds to each treatment is assessed over 24 weeks.

Who is leading STRAP?
The trial is led by the Centre for Experimental Medicine and Rheumatology at Barts and the London School of Medicine and Barts Health NHS Trust in conjunction with Queen Mary University of London.