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R4RA RNA-seq Data

The R4RA clinical trial is a stratified, biopsy-driven, open-label, phase 4 randomised controlled trial investigating response to Rituximab and Tocilizumab among Rheumatoid Arthritis (RA) patients.

This website acts as supplementary material for "Deep Molecular Pathology Profiling of Synovial Tissue Biopsies in the R4RA Randomised Clinical Trial Identifies Predictive Signatures of Response/Resistance to Biologic Treatment in Rheumatoid Arthritis". It allows users to explore RNA-seq data from the R4RA trial. Biopsies were taken at baseline (visit 1) and 16 weeks (visit 7) with accompanying clinical data available at: baseline, 16 weeks and 24 weeks (visit 9).

R4RA Publications

  • Frances Humby, Patrick Durez, Maya H Buch, Myles J Lewis, Hasan Rizvi, Felice Rivellese, Alessandra Nerviani, Giovanni Giorli, Arti Mahto, Carlomaurizio Montecucco, Bernard Lauwerys, Nora Ng, Pauline Ho, Michele Bombardieri, Vasco C Romão, Patrick Verschueren, Stephen Kelly, Pier Paolo Sainaghi, Nagui Gendi, Bhaskar Dasgupta, Alberto Cauli, Piero Reynolds, Juan D Cañete, Robert Moots, Peter C Taylor, Christopher J Edwards, John Isaacs, Peter Sasieni, Ernest Choy, Costantino Pitzalis and the R4RA collaborative group "Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial." The Lancet 397.10271 (2021): 305-317. PMID: 33485455. DOI: 10.1016/S0140-6736(20)32341-2
  • Felice Rivellese, Anna E. A. Surace, Katriona Goldmann, Elisabetta Sciacca, Cankut Çubuk, Giovanni Giorli, Christopher R. John, Alessandra Nerviani,
Liliane Fossati-Jimack, Georgina Thorborn, Ahmed Manzoor, Edoardo Prediletto,
Sarah E. Church, Briana M. Hudson, Sarah E. Warren, Paul M. McKeigue, Frances Humby, Michele Bombardieri, Michael R. Barnes, Myles J Lewis, Costantino Pitzalis and the R4RA collaborative group. "Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial."  Nature Medicine (2022). DOI: 10.1038/s41591-022-01789-0

Patrick Durez, Maya H. Buch, Hasan Rizvi, Arti Mahto, Carlomaurizio Montecucco, Bernard Lauwerys, Nora Ng, Pauline Ho, Vasco C Romão, Patrick Verschueren, Stephen Kelly, Pier Paolo Sainaghi, Nagui Gendi, Bhaskar Dasgupta, Alberto Cauli, Piero Reynolds, Juan D Cañete, Robert Moots, Peter Taylor, Christopher J Edwards, John Isaacs, Peter Sasieni, Ernest Choy, Charlotte Thompson, Serena Bugatti, Mattia Bellan, Mattia Congia, Christopher Holroyd, Arthur Pratt, João Eurico Cabral da Fonseca, Laura White, Louise Warren, Joanna Peel, Rebecca Hands, Gaye Hadfield, Julio Ramirez, Raquel Celis

Other Resources and Publications

Associated Software

Shiny Website

The shiny website was implemented by Myles Lewis, Katriona Goldmann, Cankut Çubuk, Tom Bradford and Vitaly Kukchenkov.
emr logo c4tb logo QMUL logo R4RA logo

R4RA RNA-seq Data

The R4RA clinical trial is a stratified, biopsy-driven, open-label, phase 4 randomised controlled trial investigating response to Rituximab and Tocilizumab among Rheumatoid Arthritis (RA) patients.

This website acts as supplementary material for "Deep Molecular Pathology Profiling of Synovial Tissue Biopsies in the R4RA Randomised Clinical Trial Identifies Predictive Signatures of Response/Resistance to Biologic Treatment in Rheumatoid Arthritis". It allows users to explore RNA-seq data from the R4RA trial. Biopsies were taken at baseline (visit 1) and 16 weeks (visit 7) with accompanying clinical data available at: baseline, 16 weeks and 24 weeks (visit 9).

R4RA Publications

  • Frances Humby, Patrick Durez, Maya H Buch, Myles J Lewis, Hasan Rizvi, Felice Rivellese, Alessandra Nerviani, Giovanni Giorli, Arti Mahto, Carlomaurizio Montecucco, Bernard Lauwerys, Nora Ng, Pauline Ho, Michele Bombardieri, Vasco C Romão, Patrick Verschueren, Stephen Kelly, Pier Paolo Sainaghi, Nagui Gendi, Bhaskar Dasgupta, Alberto Cauli, Piero Reynolds, Juan D Cañete, Robert Moots, Peter C Taylor, Christopher J Edwards, John Isaacs, Peter Sasieni, Ernest Choy, Costantino Pitzalis and the R4RA collaborative group "Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial." The Lancet 397.10271 (2021): 305-317. PMID: 33485455. DOI: 10.1016/S0140-6736(20)32341-2
  • Felice Rivellese, Anna E. A. Surace, Katriona Goldmann, Elisabetta Sciacca, Cankut Çubuk, Giovanni Giorli, Christopher R. John, Alessandra Nerviani,
Liliane Fossati-Jimack, Georgina Thorborn, Ahmed Manzoor, Edoardo Prediletto,
Sarah E. Church, Briana M. Hudson, Sarah E. Warren, Paul M. McKeigue, Frances Humby, Michele Bombardieri, Michael R. Barnes, Myles J Lewis, Costantino Pitzalis and the R4RA collaborative group. "Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial."  Nature Medicine (2022). DOI: 10.1038/s41591-022-01789-0
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This shows a three-way differential gene expression analysis on baseline synovial biopsies of patients classified considering treatment switch: patients who responded to rituximab after failing tocilizumab (pro-RTX, blue), patients who responded to Tocilizumab after failing Rituximab (pro-TOC, yellow) and patients who failed both drugs sequentially (refractory, red).

Blue genes have a significant change (q < 0.05) in patients who failed tocilizumab but responded to rituximab (pro-RTX).

Gold genes indicate a significant change in patients who failed rituximab but responded to tocilizumab (pro-TOC).

Green genes indicate significance in pro-RTX and pro-TOC patients.

Red genes are significantly upregulated in refractory patients, who failed both drugs.

Grey genes are not significantly changed, or not specific for any group of patients.





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