This is a open labelled, randomised clinical trial in anti-TNF alpha inadequate responders to investigate the mechanisms of response, resistance and relapse to Rituximab (R4) versus Tocilizumab in Rheumatoid arthritis (RA): developing a novel biopsy-based diagnostic tool for patient stratification. Patients who fail to respond to anti-TNF alpha drugs will be recruited to this study. They will undergo a synovial biopsy at baseline, prior to randomisation. Patients will subsequently be stratified in to 3 groups (B Cell Poor, B Cell Rich, Germinal Centres (GC) Rich) according to the following B-cell score prior to therapeutic intervention. They will then be randomized to receive Rituximab or Tocilizumab
We aim to recruit 180 patients over a period of 33 month period.
The primary outcome measure is the mean change in the clinical disease activity index (CDAI) score at 4 months compared to baseline.
Secondary outcome measures include:
In addition to the clinical outcome measures, this study also has exploratory outcomes which will investigate whether Rituximab therapy modulates synovial ectopic lymphoneogenesis and whether this determines clinical response. We will also investigate cytokine expression, B-cell clonal relationships and associated signatures in order to ascertain markers of response / resistance in the synovium and peripheral blood.