biostudies-literatureLewis MJMedical Research CouncilNational Institute for Health Research (NIHR)DH | NIHR | Efficacy and Mechanism Evaluation Programme (NIHR Efficacy and Mechanism Evaluation Programme)5374https://www.ebi.ac.uk/biostudies/studies/S-EPMC12223067biostudies-literatureUnknown16(1)Approximately 40% of patients with rheumatoid arthritis do not respond to individual biologic therapies, while biomarkers predictive of treatment response are lacking. Here we analyse RNA-sequencing (RNA-Seq) of pre-treatment synovial tissue from the biopsy-based, precision-medicine STRAP trial (n = 208), to identify gene response signatures to the randomised therapies: etanercept (TNF-inhibitor), tocilizumab (interleukin-6 receptor inhibitor) and rituximab (anti-CD20 B-cell depleting antibody). Machine learning models applied to RNA-Seq predict clinical response to etanercept, tocilizumab and rituximab at the 16-week primary endpoint with area under receiver operating characteristic curve (AUC) values of 0.763, 0.748 and 0.754 respectively (n = 67-72) as determined by repeated nested crosNature communicationsDeep molecular profiling of synovial biopsies in the STRAP trial identifies signatures predictive of treatment response to biologic therapies in rheumatoid arthritis.PMC12223067Barts Biomedical Research Centre131575MR/V012509/1MR/K015346/1Fossati-Jimack LSciacca ECarlucci FBuch MHHumby FGiorli GMaskall DFonseca JESainaghi PPGremese ESasieni PMarcia SChinoy HDasgupta BStratton RThorburn GRamirez JRivellese FMcKay NDPratt AGMachado ARMahto ATan GCuervo Avan der Heijde DCanete JDBuckley CDGithinji MLewis MJGorman CBombardieri MNerviani ARawlings CFiler AHo Pde Bellefon LMPereira JPCelis RAlivernini SLandewe RDurez PEdwards CJRomao VKelly STaylor PCRizvi HPurkayastha NMillar NBarton ACubuk CHolroyd CGendi NIsaacs JDGalloway JChoy EEhrenstein MRJaworska ECongia MSTRAP collaborative groupNg NMarini SPeel JMcInnes IZayat AHands-Greenwood RLau RRaizada SSurace AEAJadon DMosanya CPitzalis CGoldmann KLliso-Ribera GPerniola SWarren LCauli ASeth RfalseDeep molecular profiling of synovial biopsies in the STRAP trial identifies signatures predictive of treatment response to biologic therapies in rheumatoid arthritis.Approximately 40% of patients with rheumatoid arthritis do not respond to individual biologic therapies, while biomarkers predictive of treatment response are lacking. Here we analyse RNA-sequencing (RNA-Seq) of pre-treatment synovial tissue from the biopsy-based, precision-medicine STRAP trial (n = 208), to identify gene response signatures to the randomised therapies: etanercept (TNF-inhibitor), tocilizumab (interleukin-6 receptor inhibitor) and rituximab (anti-CD20 B-cell depleting antibody). Machine learning models applied to RNA-Seq predict clinical response to etanercept, tocilizumab and rituximab at the 16-week primary endpoint with area under receiver operating characteristic curve (AUC) values of 0.763, 0.748 and 0.754 respectively (n = 67-72) as determined by repeated nested cros2025-01-01T00:00:00Z2025 Jul2026-06-02T08:46:04.551Z2026-04-16T03:12:56.156ZS-EPMC122230674060386010.1038/s41467-025-60987-9