Laura Donlin, PhD: Study Discovers New Subtypes of Rheumatoid Arthritis

Laura Donlin, PhD

Credit: Hospital for Special Surgery

A recent study has identified new subtypes of rheumatoid arthritis (RA) by evaluating molecular patterns in patient joint biopsies, providing insights into the disease's underlying biology.¹

This breakthrough, funded by the National Institutes of Health (NIH) and pharmaceutical industry partners, indicated at least 4 distinct RA subtypes, each corresponding to a unique drug target.

In an interview with HCPLive, Laura Donlin, PhD, co-senior author and co-director of the Derfner Foundation Precision Medicine Laboratory at Hospital for Special Surgery (HSS), discusses this discovery, which has the potential to transform RA treatment by allowing clinicians to personalize treatment based on a patient's specific subtype, potentially leading to more effective and faster treatment outcomes.

Can you explain the significance of identifying new subtypes of RA and how this discovery can impact the current treatment landscape?

The current treatment approach to RA follows a standardized protocol. Almost all newly diagnosed cases are treated with the same medication, yet we know from population wide studies this will not adequately treat up to half of the patients. There are then numerous medications one can consider, but finding one that will work can take months and sometimes years. We know that the sooner we find an effective medication, the better the outcome.

Our work identifying new subtypes of RA may pave the way for personalized treatment approaches. This discovery has the potential to revolutionize the current landscape of RA treatment by enabling doctors to tailor therapies based on the specific subtype a patient exhibits. This personalized approach may lead to more effective and efficient outcomes, reducing the current reliance on trial and error in treatment strategies.

What methodologies did your team use to identify these new subtypes, and what were the key findings from your research?

In this study, biopsies from patient joints were tested for all cell types using sequencing methods. The tissues from all the patients were then stratified into 6 groups based on similar combinations of cell states. For example, some patient tissues were dominated by lymphocytes while others had fewer immune cell types. This tissue-based stratification provides a more in-depth understanding of RA disease, suggesting that there are very different processes taking place within patient joints.

How do these newly identified subtypes differ from the conventional classifications of RA?

Our findings showed that synovial inflammation observed in RA patients is much more diverse than previously thought. Conventional classifications often rely on clinical symptoms and broad disease characteristics, whereas our subtypes are defined by specific molecular and cellular signatures directly inside affected joints, allowing for a more precise and personalized approach to treatment.

How might these new subtypes influence the development of more targeted and effective therapies for patients with RA?

The unique molecular profiles across patients’ joints are likely to respond quite differently to the various medications that have different drug targets. Now we should be able to start determining which medications are more effective for each subtype of RA.

Could these subtypes help predict disease progression or response to different treatments?

In an ideal world – yes! With further study, these subtypes have the potential to predict disease progression and response to different treatments. This indicates a shift toward a more predictive and proactive approach to managing RA, allowing for early interventions and optimized treatment plans based on an individual's subtype.

How might these findings impact future research directions or clinical trials?

The findings from this research may significantly impact future research directions and clinical trials in the field of rheumatology. The molecular-level understanding of RA subtypes opens avenues for targeted drug development and personalized medicine approaches. Future studies and trials may focus on refining and expanding these subtypes, exploring additional biomarkers, and further investigating the clinical implications of subtype-specific treatments.

Is there anything else you'd like our audience to know?

I believe this marks the foundation for a new era in the treatment of rheumatoid arthritis. It’s a step toward understanding the unique features of a patient's condition so that we can select the most effective medication for patients right from the start, and I’m hopeful that these results will lead to new standards of personalized care for RA.

References

1. ^{Zhang F, Jonsson AH, Nathan A, et al. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. 2023;623(7987):616-624. doi:10.1038/s41586-023-06708-y}