[ISRCTN97443826] [EudraCT: 2012-002535-28] [NIHR CRN Portfolio Study ID: 14524]
Status: Closed to recruitment
Evidence from PEEAC (see above), in which synovial biopsies have been taken from patients with early arthritis, indicate that there are at least three distinct histo-morphological subtypes. These are described as fibroblast (pauci-immune), lymphoid (B-cell rich, with or without germinal center formation), and Myeloid (rich in monocytes but poor in B cells), which correspond to different transcriptomic signatures.
The purpose of this study was to test the hypothesis that the presence or absence of specific synovial and molecular signatures (B-cells and B-cell associated signatures), assessed through obtaining tissue from a synovial biopsy, will enrich for response / non-response to Rituximab, and B-cell depleting anti-CD20 monoclonal antibody. Patients were eligible if they had failed anti-TNF therapy and underwent a synovial biopsy. Patients were randomised to receive Rituximab or Tocilizumab.
This was a multi-site, international clinical trial, 12 UK and 8 EU sites recruited 164 patients between February 2013 and November 2017. The results of this trial, the first biopsy-driven RCT in RA, were published in The Lancet in January 2021 which can be found here.
This study was funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program (NIHR EME).
In R4-RA, following a synovial biopsy, anti-TNF-ir patients were randomised to Rituximab or Tocilizumab. In addition to the US-guided synovial biopsy at baseline R4RA collected a second biopsy at primary end-point in 1/3 of patients as well as matched serum/plasma, DNA, RNA, cryopreserved peripheral blood mononuclear cells (PBMCs) 3 monthly, linked to stringent clinical outcome measures including US synovitis & PDU scores. 164 patients were recruited and randomised to the R4RA trial, 2427 visits performed, with 164 baseline and 74 follow-up synovial biopsies collected. During the trial blood samples were collected for 1394 time-points, and 790 ultrasounds and 395 X-rays were collected and centrally analysed.