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Access through your institution Buy or subscribe The results of R4-RA, the first biopsy-driven, multicentre randomized controlled trial (RCT) in rheumatoid arthritis (RA), suggest that

direct assessment of synovial tissue pathology could be used to guide the choice of treatment for patients with RA. If replicated and validated in independent cohorts, the findings could

represent an important step forward in precision medicine for the disease. The R4-RA investigators focused on the extent of B cell infiltration in the RA joint tissue (synovium) as a

predictor of an individual patient’s responsiveness to a treatment that targets B cells. “In prior studies, we identified that approximately 40% of patients have few B cells infiltrating the

synovium while still displaying active arthritis,” says co-author Felice Rivellese. “On this basis, we hypothesized that, in these patients, joint inflammation is driven by alternative cell

types and/or pathways and they would be less likely to respond to the B cell depleting biologic rituximab and more likely to respond to a different biologic, such as tocilizumab.” This

hypothesis was supported by the results of a small pilot study of patients with established RA and an inadequate response to TNF inhibitor therapy, in which having few or no CD20+ B cells

was an independent predictor of non-response to rituximab. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature

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ARTICLE * Humby, F. et al. 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. _Lancet_ 397, 305–317 (2021) Article  CAS  Google Scholar  RELATED ARTICLE * Pitzalis, C. et al. Transforming clinical trials in

rheumatology: towards patient-centric precision medicine. _Nat. Rev. Rheumatol._ 16, 590–599 (2020) Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Nature Reviews Rheumatology http://www.nature.com/nrrheum/ Sarah Onuora Authors * Sarah Onuora View author publications You can also search for this author inPubMed Google Scholar

CORRESPONDING AUTHOR Correspondence to Sarah Onuora. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Onuora, S. Biopsy-driven trial a milestone towards

precision medicine in RA. _Nat Rev Rheumatol_ 17, 187 (2021). https://doi.org/10.1038/s41584-021-00599-x Download citation * Published: 10 March 2021 * Issue Date: April 2021 * DOI:

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