‘Pathogenic insights’ may help stratify Sjögren’s patients and inform treatment decisions
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DESTIN, Fla. — Stratifying Sjögren’s disease patients by symptoms or biologic parameters may help rheumatologists hit therapeutic targets, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“Stratification of Sjögren’s disease patients is a really exciting topic right now,” Sara S. McCoy, MD, PhD, an associate professor in the department of medicine, the division of rheumatology, at the University of Wisconsin-Madison School of Medicine, told attendees.
She then noted why understanding how to stratify patients is so critical at this current moment. “For the first time in decades, we have some therapeutics that might be effective in Sjogren’s disease,” she said.
Addressing the ‘Cardinal Symptoms’
While Sjögren’s disease can be marked by a wide variety of symptoms, the top three “cardinal symptoms” are dryness, pain and fatigue, according to McCoy.
McCoy said that including other symptoms of the disease, from depression and brain fog to lung, kidney, joint or gastrointestinal involvement, can help clinicians use current therapies more effectively. “I think we can do even better by grouping patients into endotypes, or biologically similar groups,” she said. “It might help patient-provider relationships and increase patient satisfaction.”
Recent research has suggested that patients may be divided into four main symptomatic groups: those with low symptom burden, those with high symptom burden, those with dryness dominant disease plus fatigue and those with pain dominant disease plus fatigue.
Understanding how these endotypes interact on a deep level with peripheral blood, transcriptomic and biologic features is still coming into view.
Researchers are currently reviewing trials of various medications and approaches in Sjögren’s disease with the aim of gaining insight into associations between symptom burden and outcomes. “By reevaluating failed clinical trials by stratifying patients using the symptom burden and what patients experience in their disease, maybe we could select more effective therapies,” McCoy said.
Quality of Life Issues
She then discussed some trends that may be useful for rheumatologists to consider.
For example, some data have shown that patients with high symptom burden are more likely to experience depression and worse QoL outcomes.
High symptom burden patients are also more likely to be treated with cholinomimetics, disease-modifying antirheumatic drugs, NSAIDs or biologic therapies. However, they commonly have less dryness and fewer laboratory or pathology abnormalities. Whether this is because they are being treated more aggressively or for some other reason is currently unknown. “It might actually be symptoms that are driving our treatment decisions,” McCoy said.
While patients with low symptom burden do not experience depression or QoL outcomes as frequently, biologic analysis has revealed some alarming trends. “Despite their low symptom burden, these patients have shown a lot of immunologic activity,” McCoy said.
Analysis of the dryness dominant group demonstrated higher levels of synovitis. “The dryness group had the highest rheumatoid factor and immunoglobulins,” McCoy said. “We are generating a picture here.”
Regarding patients with pain-dominant disease, some have demonstrated lower interferon levels, while others have demonstrated a mature B-cell profile, according to McCoy. This information may be used to guide treatment decisions.
That said, trials of medications like hydroxychloroquine or B-cell depleting therapies like rituximab (Rituxan, Genentech) have yielded inconclusive results.
But experts like McCoy are looking more closely at peripheral transcriptomics with the hope of correlating symptom burden and biologic information to treat patients based on their individual profile. “This is where we are really starting to explode with our research,” she said.
While there is much work to be done, McCoy is hopeful for the future for patients with this disease. “We are hoping that increasing understanding of pathogenic insights into Sjögren’s disease endotypes will yield improved care for these patients and insight into this disease,” she said.
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McCoy S. Sjögren’s disease cluster subtypes: What are they and are they useful to predict treatment, end organ or laboratory abnormalities? Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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