Molecular-level analyses needed
This 2021 study showed – and this most recent study further confirmed – that “histology is not the way to understand what’s going on with or be predictive with tissue,” said Harris R. Perlman, PhD, chief of rheumatology at Northwestern University in Chicago. He was not involved with the research.
Dr. Perlman
Dr. Harris R. Perlman
“Most people now believe that you really have to understand the tissue on a single-cell basis – using the gene expression of each individual cell – to really give you an idea of what’s happening in tissue,” he noted.
“RA continues to tell us that it is more complex than just something dichotomous,” added Elena Myasoedova, MD, PhD, director of the Inflammatory Arthritis Subspecialty Group at the Mayo Clinic in Rochester, Minn. She was not involved with the work.
Dr. Myasoedova
Dr. Elena Myasoedova
“Understanding more about the heterogeneity using different ‘-omics’ approaches and introducing a two- or three-dimensional approach with spatial biology can be helpful,” she said.
Spatial transcriptomics, for example, allows scientists to measure all gene activity in a tissue sample and to map where that gene activity is occurring.
“It helps us to understand and visualize molecules and their unique context within individual cells and tissues,” Dr. Myasoedova explained.
With advanced molecular analyses already available, Dr. Perlman is adamant that synovial tissue remains the key to unlocking precision medicine.
“The tissue is the golden ticket,” he said, “but it’s how you analyze it.”
And it’s clear that older analytic methods – such as histology – are not enough, he said.
A larger study of a size similar to that of STRAP that incorporates multiple sources of patient information, from gene expression to clinical symptoms, to create a predictive model would be key to understanding how to move the field of precision treatment for RA forward, he added.
“Precision medicine for RA is close,” he said. “We still have to get the numbers.”
The STRAP and STRAP-EU trials were jointly funded by the UK Medical Research Council and Versus Arthritis. Pfizer and Roche donated the study drugs through an investigator-sponsored research grant. Many authors, including Dr. Pitzalis, have multiple financial relationships with pharmaceutical companies. Dr. Van der Helm-van Mil and Dr. Myasoedova have disclosed no relevant financial relationships. Dr. Perlman consults for AbbVie, AnaptysBio, Exagen, Janssen, and Kiniksa.
A version of this article first appeared on Medscape.com.