Symptom-Based Cluster Analysis Categorizes Sjögren's Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance.

OBJECTIVE: Although symptom relief is a critical aspect for successful drug development in Sjögren's disease, patient experiences with Sjögren's-related symptoms are understudied. Our objective was to determine how pain, dryness, and fatigue, the cardinal symptoms of Sjögren's disease, drive cluster phenotypes. METHODS: We used data from the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry and a Sjögren's Foundation survey. We performed hierarchical clustering of symptoms by levels of dryness, fatigue, and pain. Using international and US cohorts, we performed multiple logistic regression analysis to compare the clusters, which included comparisons of differences in symptoms, quality of life (QoL), medication use, and systemic manifestations. RESULTS: Four similar clusters were identified among 1,454 SICCA registrants and 2,920 Sjögren's Foundation survey participants: 1) low symptom burden in all categories (LSB); 2) dry with low pain and low fatigue (DLP); 3) dry with high pain and low to moderate fatigue (DHP); and 4) high symptom burden in all categories (HSB). Distribution of SICCA registrants matching the symptom profile for each cluster was 10% in the LSB cluster, 30% in the DLP cluster, 23% in the DHP cluster, and 37% in the HSB cluster. Distribution of survey participants matching the symptom profile for each cluster was 23% in the LSB cluster, 14% in the DLP cluster, 21% in the DHP cluster, and 42% in the HSB cluster. Individuals in the HSB cluster had more total symptoms and lower QoL but lower disease severity than those in the other clusters. Despite having milder disease as measured by laboratory tests and organ involvement, individuals in the HSB cluster received immunomodulatory treatment most often. CONCLUSION: We identified 4 symptom-based Sjögren's clusters and showed that symptom burden and immunomodulatory medication use do not correlate with Sjögren's end-organ or laboratory abnormalities. Findings highlight a discordance between objective measures and treatments and offer updates to proposed symptom-based clustering approaches.

A comprehensive overview of living with Sjögren's: results of a National Sjögren's Foundation survey.

To gain insight into the Sjögren's disease (SjD) patient experience using a survey generated by patients and providers. We evaluated the results of the 2016 Sjögren's Foundation survey, with 25 questions designed in a collaborative effort between the Foundation, patients with SjD, SjD provider experts, and a marketing research company. We used descriptive statistics to provide a thorough understanding of SjD demographics, symptoms, quality of life (QoL), cost, and treatments. Analyses revealed high symptoms, QoL, and financial burdens in SjD. Dry mouth and eye were the most commonly reported symptoms (94 and 93%, respectively). The most frequent extra-glandular symptoms included fatigue, dry or itchy skin, and morning stiffness. The top three aspects of QoL most impaired included (i) sex life (53%), (ii) participating in hobbies/social activities/extracurricular activities (52%), and (iii) job/career or ability to work (49%). SjD respondents commonly reported taking health food supplements/remedies, vitamin D, and exercising, in addition to taking treatments for symptomatic dryness. SjD costs were high, including a total yearly cost, on average, of $2026 for dental care. SjD respondents reported that dryness and risk factors for lymphoma and fatigue are essential to address with new therapies. In this comprehensive overview of the SjD experience, we demonstrated a high burden of disease to SjD respondents, including symptoms, QoL, and financial burden. We also identify the top goals of therapy for new systemic SjD therapies. Key Points • The top three symptoms or signs that patients with Sjögren's hope new treatments will address are dryness, fatigue, and reduction in lymphoma or blood cancer risk • The top aspects of quality of life reported to be impaired by Sjögren's are sex life, hobbies, social activities and extracurricular activities, job/career or ability to work, and finding the correct word during conversations • Patients with Sjögren's have a yearly mean dental cost of $2026 but also have high costs associated with prescription medications, healthcare appointments, over-the-counter medications, alternative therapies, and medical equipment.