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Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.
Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.
“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.
The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
Symptom clusters verify smaller study’s findings
Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.
In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.
They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.
In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.
They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:
- Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
- Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
- Cluster 3 patients (34%) had predominant high dryness and fatigue.
- Cluster 4 patients (14%) had low symptom burden.
“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.
For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.
“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.
The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.
In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.
The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).
Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.
The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
Opportunity to tailor practice and research
During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.
“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”
Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.
Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.
The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.
SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.
Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.
Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.
“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.
The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
Symptom clusters verify smaller study’s findings
Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.
In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.
They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.
In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.
They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:
- Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
- Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
- Cluster 3 patients (34%) had predominant high dryness and fatigue.
- Cluster 4 patients (14%) had low symptom burden.
“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.
For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.
“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.
The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.
In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.
The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).
Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.
The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
Opportunity to tailor practice and research
During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.
“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”
Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.
Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.
The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.
SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.
Patients with Sjögren’s syndrome can be categorized into four distinct symptom clusters – independent of age, sex, and some disease manifestations – that may both improve symptom relief and aid in the development of targeted therapies, investigators reported.
Analysis of data from a survey conducted by the Sjögren’s Foundation identified four symptom clusters based on the grouping of five common characteristics: anxiety, depression, pain, fatigue, and dryness, Sara S. McCoy, MD, of the University of Wisconsin–Madison, and colleagues reported.
“Verification of features unique to each Sjögren’s cluster might provide guidance for future cluster-targeted therapy,” Dr. McCoy said in an oral abstract presentation during the virtual annual meeting of the American College of Rheumatology.
The dearth of Food and Drug Administration–approved disease-modifying therapies for Sjögren’s syndrome can be attributed in part to the small number of patients with extraglandular disease manifestations, the heterogeneity of disease, and the failure of available therapy to improve common symptoms such as fatigue, dryness, quality-of-life decrements, anxiety and depression, she said.
Symptom clusters verify smaller study’s findings
Dr. McCoy and colleagues explored whether symptom clusters identified in a 2019 study from the United Kingdom would apply to a larger U.S. population.
In the U.K. study, Jessica R. Tarn, PhD, and colleagues performed a hierarchical cluster analysis to identify subgroups among 608 patients in the U.K. Primary Sjögren’s Syndrome Registry and in 396 patients in two independent validation cohorts from Norway and France.
They identified four subgroups they categorized as low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue, and reported that the groups showed significant difference in serum and transcriptomic markers.
In the U.S. study, McCoy et al. sought to verify the symptom-based cluster and report on differences in key measures between the groups. They used data from a survey by the Sjögren’s Foundation of 2,961 adults with self-reported Sjögren’s syndrome. The investigators then used an unsupervised hierarchical clustering method to identify the optimal phenotypically similar clusters based on patient-reported severity of anxiety (from never to daily), depression (never to daily), pain on a visual analog scale (0 to 10), fatigue on a VAS, and dryness on a VAS. They collected data on demographics, medications, quality of life, and Sjögren’s-specific symptom frequency and systemic manifestations within each cluster, and identified cluster differences controlled for age, sex, race, and Social Security disability.
They identified four symptom-based clusters from 2,806 participants for whom complete data on the five key symptoms were available:
- Cluster 1 patients (prevalence, 30%) had high symptom burden in all categories.
- Cluster 2 patients (22%) had high anxiety and depression (22%), with some fatigue.
- Cluster 3 patients (34%) had predominant high dryness and fatigue.
- Cluster 4 patients (14%) had low symptom burden.
“We found that clusters differed in Sjögren’s-specific symptoms,” Dr. McCoy said.
For example, patients in the high-symptom-burden cluster had, as the name implies, an overall higher burden of symptoms among all major ocular, oral, and other dryness symptoms, as well as systemic organ system symptoms, whereas patients in the low-symptom-burden group consistently had the lowest levels of symptoms across the spectrum.
“We also noticed significant differences in systemic medication use. High symptom burden and high dryness and fatigue had higher use of systemic therapies targeting dryness, as might be expected,” she said.
The highest corticosteroid use was in the high-symptom-burden group, while hydroxychloroquine use was highest in the high-anxiety/depression group. Antidepressant use was also high in these two groups.
In addition, 35% of patients in the high-symptom-burden group used prescription opioid analgesics, compared with just 7% in the low-symptom-burden group.
The categories from low to high symptom burden also significantly correlated with quality-of-life measures, including Social Security Disability enrollment, emotional burden of disease, effects of disease on independence, and effects of Sjögren’s on relationships with family and friends (P < .001 for all).
Systemic manifestations of disease differed significantly among the groups for inflammatory arthritis, interstitial lung disease, and neuropathy, but there were no significant differences in the incidence of leukopenia or lymphoma.
The investigators plan to perform symptom-based cluster analysis with validated Sjögren’s syndrome populations, and propose studies to define phenotypic features of distinct clusters “to better define subsets of this heterogeneous disease, and ultimately inform targeted therapy,” Dr. McCoy concluded.
Opportunity to tailor practice and research
During the question-and-answer period following the presentation, Gabriela Hernandez-Molina, MD, of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, commented that “fatigue and pain might be also attributed to other comorbidities in these patients such as fibromyalgia,” and asked Dr. McCoy to comment on that.
“That’s exactly what we’re driving at,” Dr. McCoy replied. “Fatigue and pain frequently affect how patients experience their disease, and it would be beneficial to take this into account when we evaluate patients, and also for the studies that we’re performing, as well as future ‘-omic’ studies – transcriptomics and what-not – there’s potential here to take that type of patient we frequently see and try to tailor our clinical practice and our research to clearly what we’re seeing in practice, which is these other comorbidities.”
Dana DiRenzo, MD, from Johns Hopkins University, Baltimore, who moderated the session, asked how the information is changing the management of patients with Sjögren’s syndrome in clinic.
Dr. McCoy said that the study was based on self-reported data that can introduce bias, and that she and colleagues plan to validate the results before applying them to clinical care.
The study was supported by grants from the National Institutes of Health and the University of Wisconsin. Dr. McCoy disclosed consulting fees from Novartis and Bristol-Myers Squibb. Dr. Hernandez-Molina and Dr. DiRenzo reported no relevant disclosures.
SOURCE: McCoy SS et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1504.
FROM ACR 2020