Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

CLINICAL TRIALS

Biopsy-driven trial a milestone towards precision medicine in RA

Nature Reviews Rheumatology volume 17, page 187 (2021)Cite this article

Subjects

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

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

Original 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

  1. Nature Reviews Rheumatology http://www.nature.com/nrrheum/

    Sarah Onuora

Authors
  1. Sarah Onuora
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah Onuora.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41584-021-00599-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing