A synovial biopsy–driven trial in rheumatoid arthritis

A B cell–depleting therapy is less effective in patients with low synovial B cell gene expression.
Saheli Sadanand is a senior editor at Nature Medicine, covering the areas of immunology, rheumatology and immunotherapies.

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Some patients with rheumatoid arthritis respond to treatment with rituximab, a B cell–depleting antibody given after other therapies fail, whereas others show poor responses. At present there are no reliable blood biomarkers that can help in the prediction of rituximab’s efficacy.

Pitzalis and colleagues conducted a randomized clinical trial to determine whether the relative abundance of B cells in the synovium, the soft tissue surrounding the joints and the initial site of inflammation, before treatment is related to the response to rituximab versus the response to tocilizumab, a therapy that targets the cytokine receptor IL-6R.

The authors found no significant difference between the treatment groups’ response rates when they measured synovial B cells via histology. However, patients with limited B cell gene expression, as quantified by RNA sequencing, had significantly greater treatment responses to tocilizumab.

These data suggest that RNA sequencing might be more sensitive than histology for assessing pre-treatment synovial B cell abundance and for predicting responses to rituximab. This sequencing approach could be useful for personalizing treatment for patients with rheumatoid arthritis.

The Lancet (2021)

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