{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":[null],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-13733"],"description":["Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients recruited into the STRAP randomised clinical trial: RNA-Seq data from 210 patients at baseline. Patients were randomly assigned to etanercept, tocilizumab and rituximab. For the full study protocol and baseline patient characteristics see: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00241-2/fulltext"],"repository":["biostudies-arrayexpress"],"sample_protocol":["Library Construction - RNA sequencing library preparation used the NEBNext Ultra II RNA Library Prep Kit for Illumina followed by manufacturer’s instructions (NEB, Ipswich, MA, USA). Briefly, mRNA were first enriched with Oligod(T) beads. Enriched mRNAs were fragmented for 15 minutes at 94 °C. First strand and second strand cDNA were subsequently synthesized. cDNA fragments were end repaired and adenylated at 3’ends, and universal adapters were ligated to cDNA fragments, followed by index addition and library enrichment by PCR with limited cycles. The sequencing library was validated on the Agilent 4200 TapeStation (Agilent Technologies, Palo Alto, CA, USA), and quantified by using Qubit 2.0 Fluorometer (Invitrogen, Carlsbad, CA).","Sequencing - The sequencing libraries were clustered on a single lane of a flowcell. After clustering, the flowcell was loaded on the Illumina NovaSeq6000 instrument according to manufacturer’s instructions. The samples were sequenced using a 2x150 Paired End (PE) configuration. Image analysis and base calling were conducted by the NovaSeq Control Software (HCS). Raw sequence data (.bcl files) generated from Illumina NovaSeq was converted into fastq files and de- multiplexed using Illumina's bcl2fastq 2.20 software. One mismatch was allowed for index sequence identification.","Sample Treatment - For the full study protocol and baseline patient characteristics see Rivellese et al., 2023 https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00241-2/fulltext","Sample Collection - Patients underwent a synovial biopsy of a clinically active joint (clinically swollen and with ultrasound synovial thickening ≥2) before starting trial therapy.","Nucleic Acid Extraction - A minimum of 6 synovial samples per patient were immediately immersed in RNA-Later and RNA was extracted from synovial tissue using Qiagen Micro AllPrep RNA/DNA extraction kit. Briefly, 1-10mg of tissue was lysed using RLT buffer with addition of β-Mercaptoethanol, and then sheared using Qiagen TissueLyser II machine.Tissue lysate was then run through the kit columns set. Columns were washed using the appropriate kit wash buffers before RNA was eluted and re-suspended in RNAse free water. For more details see: https://www.thelancet.com/cms/10.1016/S2665-9913(23)00241-2/attachment/94785fe7-25eb-4792-8ea3-501537b9c5bc/mmc1.pdf"],"figure_sub":["MINSEQE Score","Assays and Data","organisation","MAGE-TAB Files"],"data_protocol":["Data Transformation - Tximport version 1.22.0 was used to aggregate the transcript level expression data to genes, counts were then subject to variance stabilizing transformation (VST) and transcripts per million (TPM) using the DESeq2 version 1.34.0 package and in-house script, respectively.","Sequence Alignment - Transcripts were then quantified using Salmon version 0.13.1 and an index generated from the Gencode release 29 (GRCh38.p12) transcriptome following the standard operating procedure."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq 6000"],"pubmed_abstract":["<h4>Background</h4>Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status.<h4>Methods</h4>STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)-European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU).<h4>Findings</h4>Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47-2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53).<h4>Interpretation</h4>In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response.<h4>Funding</h4>UK Medical Research Council and Versus Arthritis."],"study_type":["RNA-seq of coding RNA"],"species":["Homo sapiens"],"pubmed_title":["Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials"],"additional_accession":["E-MTAB-11611"],"pubmed_authors":["Felice Rivellese, Alessandra Nerviani, Giovanni Giorli, Louise Warren, Edyta Jaworska, Michele Bombardieri, Myles J Lewis, Frances Humby, Arthur G Pratt, Andrew Filer, Nagui Gendi, Alberto Cauli, Ernest Choy, Iain McInnes, Patrick Durez, Christopher J Edwards, Maya H Buch, Elisa Gremese, Peter C Taylor, Nora Ng, Juan D Cañete, Sabrina Raizada, Neil D McKay, Deepak Jadon, Pier Paolo Sainaghi, Richard Stratton, Michael R Ehrenstein, Pauline Ho, Joaquim P Pereira, Bhaskar Dasgupta, Claire Gorman, James Galloway, Hector Chinoy, Désirée van der Heijde, Peter Sasieni, Anne Barton, Costantino Pitzalis, on behalf of the STRAP collaborative group","Dr. Cankut Cubuk","Prof. Myles Lewis"]},"is_claimable":false,"name":"RNA-Seq of synovial tissue biopsies from individuals with rheumatoid arthritis from the STRAP randomised clinical trial","description":"Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients recruited into the STRAP randomised clinical trial: RNA-Seq data from 210 patients at baseline. Patients were randomly assigned to etanercept, tocilizumab and rituximab. For the full study protocol and baseline patient characteristics see: https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00241-2/fulltext","dates":{"release":"2025-04-28T00:00:00Z","modification":"2026-06-05T06:45:31.117Z","creation":"2024-01-24T12:35:15.113Z"},"accession":"E-MTAB-13733","cross_references":{"ENA":["ERP156842"],"Biostudies":["E-MTAB-11611"],"EFO":["EFO_0002944","EFO_0004170","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0003738","EFO_0004184","EFO_0003969"],"doi":["10.1016/S2665-9913(23)00241-2"]}}