Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-Seq of synovial tissue biopsies from individuals with rheumatoid arthritis from the R4RA randomised clinical trial

ABSTRACT: Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients who were recruited into the R4RA randomised clinical trial. Patients were randomised to treatment with rituximab or tocilizumab. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA and were eligible for treatment with rituximab therapy according to UK NICE guidelines, i.e. failing or intolerant to csDMARD therapy and at least one biologic therapy (excluding trial IMPs) were recruited when fulfilling the trial inclusion/exclusion criteria. For the full study protocol and baseline patient characteristics see Humby et al (2021) The Lancet 397(10271): 305-17. PMID: 33485455.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Dr. Cankut Cubuk

PROVIDER: E-MTAB-11611 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:TNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials, the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement. The aim of this study was to investigate global molecular patterns in synovial biopsies from RA patients obtained 12 weeks after initiation of adalimumab therapy. All patients had rheumatoid arthritis (RA), according to the American College of rheumatology criteria for the diagnosis of RA. They had active disease at the time of initiation of adalimumab therapy and were resistant to conventional therapy. They all had erosive changes imaged on conventional x-rays of the hands and/or feet. All patients were treated with disease-modifying antirheumatic drugs (DMARD’s), 23 with methotrexate (median dose 15 mg/week, range 7.5 – 20 mg/week), and 2 with leflunomide (20 mg/day); 18 of them were treated with low-dose steroids (prednisolone ≤ 7.5 mg/day). Six patients had been included in double-blind clinical trials before inclusion in the present study (1 in a Golimumab versus placebo trial, 3 in a MapKinase inhibitor versus placebo trial and 2 in a TACE-inhibitor versus placebo trial). These trials were stopped at least 3 months prior to initiation of TNF-blocking therapy. All drug dosages were stable from at least 3 months prior to initiation of TNF blocking therapy until completion of the study. No steroid injections were allowed during the duration of the study. Adalimumab therapy was initiated at a dosage of 40 mg subcutaneously every other week. Disease activity at baseline and 12 weeks after initiation of therapy (T12) was evaluated using DAS(28)-CRP (3- and 4-variables) scores, and response to therapy was assessed according to the EULAR response criteria that categorize patients in responders (good- or moderate-) and non- (or poor-) responders based on changes in DAS activity between T0 and T12 and absolute DAS values at T12. Synovial biopsies were obtained by needle-arthroscopy of knee of the patients at T12. The aim of the study was to compare gene expression profiles in synovial tissue of RA patients who responded versus not responded to adalimumab therapy.

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RNA-Seq of synovial tissue biopsies from individuals with rheumatoid arthritis from the R4RA randomised clinical trial

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