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
- Humby F, et al. (2021) 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): 305-17. DOI: 10.1016/S0140-6736(20)32341-2 PMID: 33485455
- Rivellese F, Surace AEA, Goldmann K, Sciacca E, Çubuk C, Giorli G, John CR, Nerviani A, Fossati-Jimack L, Thorborn G, Ahmed M, Prediletto E, Church SE, Hudson BM, Warren SE, McKeigue PM, Humby F, Bombardieri M, Barnes MR, Lewis MJ, Pitzalis C & the R4RA collaborative group (2022) Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nature Medicine 28: 1256-68. DOI: 10.1038/s41591-022-01789-0 PMID: 35589854
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
- The PEAC study investigates the pathobiology of early arthritis. A similar website to explore the PEAC data can be found at https://peac.hpc.qmul.ac.uk with associated pulications:
- Lewis et. al. (2019) Molecular Portraits of Early Rheumatoid Arthritis Identify Clinical and Treatment Response Phenotypes. Cell Reports 2019; 28(9):2455-2470.e5. DOI: 10.1016/j.celrep.2019.07.091 PMID: 31461658
- Humby, Lewis et al (2019) Synovial cellular and molecular signatures in early rheumatoid arthritis stratify clinical response to csDMARD therapy and predict radiographic progression. Ann Rheum Dis 2019; 78(6): 761-772. PMID: 30878974.
Associated Software
- Myles Lewis, Katriona Goldmann and Elisabetta Sciacca (2021). glmmSeq: General Linear Mixed Models for Gene-Level Differential Expression. R package. https://CRAN.R-project.org/package=glmmSeq
- Katriona Goldmann and Myles Lewis (2021). volcano3D: Interactive Plotting of Three-Way Differential Expression Analysis. R package. https://CRAN.R-project.org/package=volcano3D.
- Myles Lewis, Athina Spiliopoulou, Katriona Goldmann (2023). nestedcv: Nested Cross-Validation with 'glmnet' and 'caret'. R package. https://cran.r-project.org/package=nestedcv.
Shiny Website
The shiny website was implemented by Myles Lewis, Katriona Goldmann, Cankut Çubuk, Tom Bradford and Vitaly Kukchenkov.
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
- Humby F, et al. (2021) 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): 305-17. DOI: 10.1016/S0140-6736(20)32341-2 PMID: 33485455
- Rivellese F, Surace AEA, Goldmann K, Sciacca E, Çubuk C, Giorli G, John CR, Nerviani A, Fossati-Jimack L, Thorborn G, Ahmed M, Prediletto E, Church SE, Hudson BM, Warren SE, McKeigue PM, Humby F, Bombardieri M, Barnes MR, Lewis MJ, Pitzalis C & the R4RA collaborative group (2022) Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nature Medicine 28: 1256-68. DOI: 10.1038/s41591-022-01789-0 PMID: 35589854
The change refers to the difference from baseline i.e. change in x = xvisit 7 - xbaseline
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.