EULAR Sjögren's Syndrome Patient Reported Index Research Articles

Comprehensive analysis of the clinical manifestations and hematological parameters associated with secondary immune thrombocytopenia in patients with primary Sjögren syndrome: An observational study.

Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease that primarily affects exocrine glands and can lead to various extraglandular manifestations, including secondary immune thrombocytopenia (ITP). Understanding the clinical and hematological differences in pSS patients with and without secondary ITP is crucial for improved patient management and treatment strategies. This retrospective study, conducted from January 2020 to December 2023, involved a cohort of pSS patients, dividing them into 2 groups: those with secondary ITP and those without. Patients were evaluated using the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren Syndrome Patient-Reported Index (ESSPRI), Health Assessment Questionnaire, and other hematological parameters. Inclusion criteria were based on the American-European Consensus Group or ACR/EULAR classification criteria for pSS. Exclusion criteria included other autoimmune or hematological disorders, prior splenectomy, recent blood transfusions, and lack of informed consent. Statistical analysis was performed using SPSS software, with various tests applied to analyze the data, including logistic regression to identify risk factors for secondary ITP. Significant differences were noted in fatigue, lymphadenopathy, arthritis, mean age, and ESSDAI scores between the secondary ITP and non-secondary ITP groups. Patients with secondary ITP exhibited higher platelet counts, more prevalent lymphopenia, higher immunoglobulin G (IgG) levels, lower complement 3 levels, and reduced white blood cell and hemoglobin levels. Logistic regression analysis identified lymphadenopathy as a risk factor and arthritis as a protective factor for the development of secondary ITP. The study reveals distinct clinical and hematological characteristics in pSS patients with secondary ITP, suggesting a higher disease activity in this subset. These findings underscore the need for further exploration of these associations to develop more precise treatment approaches for pSS, focusing on preventing secondary ITP and improving patient outcomes.

Longitudinal evaluation of major salivary gland functioning in Sjögren's disease patients in a prospective standard-of-care cohort.

To evaluate changes in major salivary gland functioning over time using salivary gland ultrasonography (SGUS), salivary flow measurements (sialometry), and patient-reported outcome measures (PROMs) in patients diagnosed with primary Sjögren's disease (SjD). Consecutive outpatients from the ongoing prospective REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort, all fulfilling the ACR-EULAR classification criteria for SjD, were included. SGUS images assessed with the Hocevar and OMERACT scoring system, unstimulated and stimulated whole saliva (UWS/SWS), unstimulated and stimulated submandibular/sublingual saliva (uSMSLS/sSMSLS) and parotid saliva, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) general dryness, oral dryness, and Xerostomia Inventory were assessed at baseline (BL), 2-year (Y2) and 5-year (Y5) follow-up. In total, BL and Y2 data were available for 253 patients and 75 patients had already reached Y5. At group level, SGUS Hocevar (i.e., mean±SD: 22±10 at BL, 22±10 at Y2 and 23±10 at Y5), OMERACT scores, UWS, SWS and PROMs remained stable over time (all p>0.05). Slightly decreased uSMSLS (p=0.025) and sSMSLS (p=0.004) were observed at Y5. At individual patient level, a similar proportion showed an increase or decrease of ≥25% for Hocevar, UWS and SWS. At baseline, poor associations were observed between SGUS and PROMs and fair associations between sialometry and PROMs. Over time, changes in objective assessments did not correlate with changes in PROMs. Overall, major salivary gland functioning assessed with SGUS, sialometry and PROMs did not change significantly up to 5 years of follow-up in a standard-of-care cohort of SjD patients from daily clinical practice.

Intraoperative Visualization and Treatment of Salivary Gland Dysfunction in Sjögren's Syndrome Patients Using Contrast-Enhanced Ultrasound Sialendoscopy (CEUSS).

In sialendoscopy, ducts are dilated and the salivary glands are irrigated with saline. Contrast-enhanced ultrasound sialendoscopy (CEUSS), using microbubbles, may facilitate the monitoring of irrigation solution penetration in the ductal system and parenchyma. It is imperative to test CEUSS for its safety and feasibility in Sjögren's syndrome (SS) patients. CEUSS was performed on 10 SS patients. The primary outcomes were safety, determined by the occurrence of (serious) adverse events ((S)AEs), and feasibility. The secondary outcomes were unstimulated and stimulated whole saliva (UWS and SWS) flow rates, xerostomia inventory (XI), clinical oral dryness score, pain, EULAR Sjögren's syndrome patient reported index (ESSPRI), and gland topographical alterations. CEUSS was technically feasible in all patients. Neither SAEs nor systemic reactions related to the procedure were observed. The main AEs were postoperative pain (two patients) and swelling (two patients). Eight weeks after CEUSS, the median UWS and SWS flow had increased significantly from 0.10 to 0.22 mL/min (p = 0.028) and 0.41 to 0.61 mL/min (p = 0.047), respectively. Sixteen weeks after CEUSS, the mean XI was reduced from 45.2 to 34.2 (p = 0.02). We conclude that CEUSS is a safe and feasible treatment for SS patients. It has the potential to increase salivary secretion and reduce xerostomia, but this needs further investigation.

Lacrimal gland ultrasonography and elastography as a diagnostic and activity tool for primary Sjögren's syndrome.

To investigate the effectiveness of 2-dimensional shear wave elastography (2D-SWE) in the assessment of lacrimal gland involvement in primary Sjögren's syndrome (pSS) and to determine the association between ultrasonographic findings and clinical activity measures. Forty-six patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria of pSS and 23 age and gender-matched healthy control subjects were enrolled. Clinical, laboratory and labial biopsy histopathologic characteristics of patients were recorded. Disease activity of pSS and severity of ocular dryness were evaluated with EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Ocular Surface Disease Index (OSDI), respectively. Parotid and lacrimal gland architectures were assessed by B-mode ultrasound and 2D-SWE techniques. Mean shear wave elastography measurements, reflecting loss of elasticity, were remarkably higher in pSS patients compared to healthy subjects both in the lacrimal and parotid glands (8.99 ± 3.45 vs 3.68 ± 1.76 in lacrimal glands and 14.14 ± 4.39 vs 7.83 ± 1.69 in parotid glands, all P < 0.001). Shear wave elasticity of lacrimal glands was correlated with OSDI and ESSPRI scores (r = 0.69; P = 0.001 and r = 0.58; P = 0.001, respectively). A cut-off value of 4.6 kPa in the lacrimal gland elasticity discriminated pSS patients from healthy subjects with a sensitivity of 94% and specificity of 87%. Results of our study suggest that lacrimal glands lose elasticity in patients with pSS and the assessment of elasticity with 2D-SWE might help to classify patients as having pSS. Further studies are needed to validate the diagnostic utility of lacrimal 2D-SWE by including diseases other than pSS.

Depression is the most significant independent predictor of fatigue in patients with primary Sjögren's syndrome.

The study aimed to evaluate the level of fatigue and the relationship between mood, pain, fibromyalgia, insomnia, disease activity, and dryness with fatigue in primary Sjögren's syndrome (PSS) patients. In this case-control study, the participants were recruited between January 2021 and July 2021. Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), pain DETECT questionnaire, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Insomnia Severity Index (ISI) were administered to 50 PSS patients (48 females, 2 males; mean age: 48.9±10.8 years; median age: 47 years; range, 29 to 71 years) and 60 healthy controls (HCs; 57 females, 3 males; mean age: 49.8±8.4 years, median age: 52 years; range, 32 to 72 years). In addition, EULAR Sjögren's syndrome disease activity index (ESSPRI), EULAR Sjögren's Syndrome Patient Reported Index (ESSDAI), pain thresholds, Schirmer tests, and whole unstimulated salivary flow rate measurements were determined in PSS patients. Independent predictors of fatigue (fatigue subscale scores <30.5) were investigated by logistic regression analysis. The frequency of fatigue in PSS patients and HCs was 54.0% and 8.3%, respectively. The rates of mood disturbance (BDI ≥11) in PSS patients with and without fatigue were 70.4% and 13.1%, respectively. BDI (Rho=-0.804), BAI (Rho=-0.586), ISI (Rho=-0.483), and ESSDAI (Rho=-0.345) were negatively correlated with the fatigue subscale score. Depression [Odds ratio (OR): 1.214, confidence interval (CI): 1.007-1.463], fibromyalgia (OR: 21.674, CI: 1.470-319.469), disease activity (OR: 1.440; CI: 1.005-2.065), and insomnia (OR: 1.223, CI: 1.003-1.4922) were identified as independent predictors of fatigue in PSS patients. It was determined that BD alone could predict fatigue by 84% in PSS patients. Depression can be a prominent predictor of fatigue in PSS patients. There is a need for studies evaluating the effect of antidepressant treatment approaches on fatigue accompanied by mood disturbance in PSS patients.

Premature stroke and cardiovascular risk in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD in pSS patients. PSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records. 61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (p < 0.05), pSS manifestations, in particular vasculitis (p = 0.033) and Raynaud's phenomenon (p = 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (n = 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (p = 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) (p = 0.048) were observed. Age at first cerebrovascular event was 55.2 [48.9-69.6] years. Multivariate analysis confirmed hypertension [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87-7.18, p < 0.001], hypercholesterinemia (OR 3.1, 95% CI 1.63-5.72, p < 0.001), male gender (OR 0.4, 95% CI 0.17-0.78, p = 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28-4.82, p = 0.007), and CNS involvement (OR 2.7, 95% CI 1.00-7.15, p = 0.048) as independent CVD predictors. Raynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.

Comparison of cutaneous silent period parameters in patients with primary Sjögren's syndrome with the healthy population and determination of ıts relationship with clinical parameters.

Small fiber neuropathy (SFN) is one of the main neurological manifestations in primary Sjögren's Syndrome (pSS). For the detection of SFN, cutaneous silent period (CSP) measurement is gaining popularity recently due to its non-invasiveness and practical application. Evaluating SFN involvement in patients with pSS using CSP and evaluating its relationship with clinical parameters. Patients with a diagnosis of pSS and healthy volunteers demographically homogeneous with the patient group were included in the study. The CSP responses were recorded over the abductor pollicis brevis muscle. The latency and duration values of the responses were obtained. In patient group, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Hospital Anxiety and Depression Scale (HADS), Short Form-36 (SF-36) questionnaire, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and Central Sensitization Inventory (CSI) were applied for the evaluation of symptom severity, mood, quality of life, presence of neuropathic pain and central sensitization, respectively. The mean CSP latency was significantly longer in patient group compared to control group (p < 0.001). Mean CSP duration was also significantly shorter in patient group (p < 0.001). There were no significant differences in CSP parameters according to patients' neuropathic pain or central sensitization profile. There were significant correlations of CSP parameters (latency and duration, respectively) with ESSPRI dryness (ρ = 0.469, p = 0.004; ρ = -0.553, p < 0.001), fatigue (ρ = 0.42, p = 0.011; ρ = -0.505, p = 0.002), pain (ρ = 0.428, p = 0.009; ρ = -0.57, p < 0.001) subscores and mean ESSPRI score (ρ = 0.631, p < 0.001; ρ = -0.749, p < 0.001). When SF-36 subscores and CSP parameters were investigated, a significant correlation was found only between "bodily pain" subscore and CSP duration (ρ = -0.395, p = 0.017). In HADS, LANSS and CSI evaluations, a significant correlation was found only between HADS anxiety score and the CSP duration (ρ = 0.364, p = 0.02). As indicated by CSP measurement, SFN is more prominent in patients with pSS than in the healthy population. It is important to investigate the presence of SFN because of its correlation with the leading symptoms in the clinical spectrum of pSS.

Patient Acceptable Symptom State (PASS) in patients with primary Sjögren's syndrome in daily clinical practice.

To explore Patient Acceptable Symptom State (PASS) in a standard of care cohort of patients with primary Sjögren's syndrome (pSS) and to compare patient characteristics including EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) between PASS and non-PASS groups. All pSS patients fulfilling ACR/EULAR classification criteria from the Registry of Sjögren's Syndrome LongiTudinal (RESULT) cohort, who had available PASS data at baseline were included. Patient-reported outcomes included the PASS question: "Considering all the different ways your disease is affecting you, if you were to stay in this state for the next few months, do you consider your current state satisfactory?"; yes: PASS / no: non-PASS. Of the 278 included pSS patients, 199 (72%) had an acceptable symptom state according to the PASS question, and median ESSPRI was 6 (IQR 4-7). In the PASS group, 118 (59%) patients had an unacceptable symptom state according to ESSPRI (score ≥5). In multivariable regression analyses, ESSPRI and disease duration were independently associated with presence of PASS. The accuracy of ESSPRI to predict PASS was fair (AUC of 0.78). The cut-off point of ESSPRI for presence of PASS with the highest Youden's index was 7.2 (sensitivity 85%, specificity 56%), followed by 5.2 (sensitivity 48%, specificity 90%). The majority of pSS patients reported being in an acceptable symptom state according to the PASS question, despite high ESSPRI scores. In our standard of care cohort, the optimal cut-off point of ESSPRI to predict PASS is different when focusing on sensitivity (±7) or specificity (±5).

PROMIS Provides a Broader Overview of Health-related Quality of Life Than the ESSPRI in Evaluation of Sjögren Syndrome.

Sjögren syndrome (SS) has a significant impact on health-related quality of life (HRQOL). We sought to evaluate how the Patient Reported Outcome Measurement Information System (PROMIS) domains in SS may supplement the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI). A cross-sectional evaluation was performed on consecutive adult patients during visits to an SS clinic between March 2018 and February 2020. Each patient completed PROMIS short forms related to HRQOL and the ESSPRI, and had a clinical assessment. Patients were either classified as SS by 2016 American College of Rheumatology (ACR)/EULAR criteria, or as "sicca not otherwise specified (NOS)" and used as a comparison group. Univariable and multivariable linear regression models were used to evaluate predictors of PROMIS fatigue (-F), pain interference (-PI), and ability to participate in social roles and activities (-APS). Two hundred twenty-seven patients with SS and 85 with sicca NOS were included and did not differ in ESSPRI domains; 26% of the SS and 20% of the sicca NOS group had concurrent autoimmune disease. In SS, PROMIS-PI, PROMIS-F, and PROMIS physical function were at least one-half SD worse than US population normative values. PROMIS-PI (r = 0.73) and PROMIS-F (r = 0.80) were highly correlated with ESSPRI pain and fatigue subdomains. Fatigue and pain interference, but not dryness or mood disturbance, were the strongest predictors of social participation in multivariable analysis. In our SS cohort, PROMIS instruments identified a high disease burden of pain interference, fatigue, and physical function. PROMIS-F strongly predicted PROMIS-APS. PROMIS-PI and PROMIS-F scores correlated highly with their respective ESSPRI domains. PROMIS instruments should be considered to identify relevant HRQOL patterns in SS.

Comparative analysis of the efficacy and safety of herbal decoction CheReCunJin alone and combined with hydroxychloroquine for treating primary Sjögren's syndrome: A randomized controlled trial

IntroductionThere is currently no established effective treatment for primary Sjögren's syndrome (pSS). Traditional Chinese Medicine (TCM) is widely used in China and is reported to improve patient symptoms. This study compare the clinical efficacy and safety of herbal decoction CheReCunJin alone and combined with hydroxychloroquine for the treatment of pSS. MethodsSeventy pSS patients without visceral involvement were randomly assigned in equal numbers to oral administration of CheReCunJin decoction only (group 1) or CheReCunJin decoction combined with hydroxychloroquine (group 2), Efficacy was evaluated after 3 months of treatment by the TCM syndrome and total effectiveness scores, European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), and Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) levels. Safety was assessed. ResultsThere were no differences in the baseline characteristics of the two groups. Compared with baseline values, the TCM syndrome, ESSPRI and ESSDAI scores, ESR, CRP, and Schirmer's test results improved significantly in both groups after treatment (p < 0.05). There was no significant difference in the TCM syndrome total effectiveness rate between the two groups (p = 0.31). Between-group differences in the changes in ESSPRI, ESSDAI, ESR, CRP, Schirmer's test, and IgG after treatment were not significant (all p> 0.05). Adverse reactions were reported in 5.88% of group 1 and 3.33% of group 2 participants (p = 0.83). ConclusionCheReCunJin decoction alone was effective and safe for the treatment of pSS. Trial registrationChinese Clinical Trial Registry: ChiCTR1800016471

AB0888-HPR EULAR SJOGREN’S SYNDROME PATIENT REPORTED INDEX-FATIGUE SCORE AND HADS-DEPRESSION SCORE MEDIATE IDENTITY SCORE OF ILLNESS PERCEPTION QUESTIONNAIRE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

Background:Dryness, fatigue, and pain are common clinical manifestations assessed by EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI)-Dryness, -Fatigue, -Pain scores in patients with primary Sjögren’s syndrome (pSS). In addition, depression is also seen in these patients owing to the pattern of the chronic disease.Objectives:The aim of the study was to assess the complex interactions among Depression status, Illness Perception, and prominent clinical manifestations evaluated by the ESSPRI (Dryness, Fatigue, and Pain) in patients with pSS.Methods:In this cross-sectional study, 111 patients with pSS (M/F: 5/106; mean age: 52.9 ± 12.01 years) were included. The data were collected by clinical examination and a questionnaire regarding patient reported outcome measures (PROMs). Unstimulated (U-WSFR) and stimulated (S-WSFR) whole saliva flow rates of patients were calculated as ml/min. Hospital Anxiety and Depression Scale (HADS), Illness Perception Questionnaire-R (IPQ-R) and EULAR Sjogren’s Syndrome Patient Reported Index were filled by patients. Increases in HADS score and subgroup scores of ESSPRI (Dryness, Fatigue and Pain) and IPQ-R dimensions regarding Identity, Consequences, and Emotional reflected poor conditions for patients. In addition, patients scored their disease activity (0: inactive-100: the worst activity) by using 100-mm visual analogue scale (VAS). After preliminary analysis, a mediation analysis was used to evaluate the relations among these variables.Results:In the study, ESSPRI-Dryness score (6,27±2,79) was associated with U-WSFR (0,40±0,57) and S-WSFR (1,04±0,86),(r:-0,4 p=0.000; r:-0,3 p=0.004). Moreover, patients reported disease activity score (48,78±26,67) was related to U-WSFR (r: -0,3 p=0.026) as well as Consequence (19,12±5,47) and Emotional (19,54±7,02) scores of IPQ-R questionnaire (r: 0,3 p=0.035; r: 0,3 p=0.014).In IPQ-R questionnaire, Identity score (8,04±3,1) reflecting number of symptoms that patients experienced due to their illness was correlated with scores of ESSPRI-Fatigue (5,29±2,97), ESSPRI-Pain (5,18±3,01), HADS-Anxiety (11,67±5,55), HADS-Depression (9,2±4,98) in the study (p&lt;0.05).In the mediation analysis, Identity score was directly mediated by ESSPRI-Fatigue score (p=0.0093) and indirectly mediated by HADS-Depression score (p=0.0011).A bootstrap analysis with 5000 replications was applied to estimate mediation effect to generate 95% CI. Percentile bootstrap of HADS-Depression was found to be an effective mediator for Identity score based on 5000 bootstrap sample.Conclusion:Both depression status and fatigue affected Identity score reflecting the number of symptoms poorly. Considering this complex relationship in disease activity assessment may positively affect disease outcomes.Disclosure of Interests:None declared

POS1486-HPR DAILY ACTIVITY IMPAIRMENT IS MEDIATED BY BOTH ORAL DRYNESS AND ORAL HEALTH RELATED QUALITY OF LIFE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

Background:Both oral functions and oral health-related quality of life (OHRQoL) are poorly affected by low salivary flow rate in patients with primary Sjögren’s syndrome (pSS).Objectives:The aim of the study was to evaluate the effects of oral dryness and OHRQoL on daily life in patients with primary Sjögren’s syndrome (pSS).Methods:In this cross-sectional study, 86 patients with pSS (M/F: 5/81; mean age: 52.4 ± 11.6 years) were included. The data were collected by clinical examination and a questionnaire regarding patient-reported outcome measures (PROMs). Patient filled PROMs regarding Oral Health Impact Profile-14 (OHIP-14) for OHRQoL, Work Productivity and Activity Impairment scale (WPAI) for Daily life and the EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) for their symptoms. Unstimulated whole saliva flow rates (U-WSFR) of patients were calculated as ml/min. Increases in PROMs and decreases in U-WSFR reflected poor conditions. After preliminary analysis, a mediation analysis was used to evaluate the relations among variables.Results:WPAI-Daily activity impairment score was higher in patients with low U-WSFR (≤0,1 ml/min) than the others (67±29,8 vs 52,5±28,6) (p=0.042). Both U-WSFR (0,43±0,57 ml/min) and ESSPRI-Dryness score (6.31 ± 2.71) were correlated with scores of OHIP-14 (25,96±17,13)(r:- 0,38 p=0.000; r: 0,37 p=0.000) and WPAI-Daily activity impairment (57,96±29,71)(r: -0,36 p=0.004; r: 0,53 p=0.000). Moreover, scores of ESSPRI-Pain (5,16±3,12) and ESSPRI-Fatigue (5,41±2,97) were also related to WPAI-Daily activity impairment score (r: 0,41 p=0.001; r:0,49 p=0.000, respectively).In the mediation analysis, WPAI-Daily activity impairment score (57.9 ± 29.7) was directly mediated by ESSPRI-Dryness score (p=0.0010) and indirectly mediated by OHIP-14 score (25.9 ± 17.1) (p=0.0357). After mediation analysis, a bootstrap analysis with 5000 replications was applied to estimate the mediation effect to generate 95% CI. Percentile bootstrap of OHIP-14 score was found to be an effective mediator for Daily activity impairment based on 5000 bootstrap samples.Conclusion:Both oral dryness and poor OHRQoL in patients with pSS affected daily activity impairment. Therefore, the patients’ needs for improving oral health were critical components of treatment plans to improve the daily activity of SjS patients.Disclosure of Interests:None declared

Go Ask Your Patients! PSS-QoL Reported Perception of Dryness Correlates With Lacrimal and Salivary Flow in Primary Sjögren's Syndrome.

Introduction/Objectives: The patient perspective is an essential outcome parameter in the quest for effective therapy in primary Sjögren's Syndrome (PSS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is recommended by EULAR to quantify patient's symptom burden and has been used in several clinical trials. Surprisingly, the patient's perception of dryness quantified with ESSPRI does not correlate with objective measures of salivary or lacrimal flow. Thus, we evaluated a newly developed assessment tool-the Primary Sjögren's Syndrome Quality of Life Questionnaire (PSS-QoL)—for quantifying symptoms of dryness in comparison with the ESSPRI and objective measurements of salivary and lacrimal flow.Methods: Data of patients from the PSS registry of the Medical University of Graz fulfilling the 2016 ACR/EULAR classification criteria for PSS were analyzed. The patient perspective was analyzed by PSS-QoL, ESSPRI, Xerostomia Inventory (XI) and Ocular Surface Disease Index (OSDI). Sicca signs were measured with Schirmer's test, unstimulated salivary flow test (USF) and stimulated salivary flow test (SSF). ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) and EGA (Evaluator Global Assessment, numeric rating scale from 0 to 10) were obtained. In addition, free light chains (FLC) κ and λ, rheumatoid factor (RF) IgM and IgA were determined.Results: Data from 123 PSS patients were analyzed; 91.9% (n = 113) were female, with a mean disease duration of 6.2 (±5.3) years and mean age of 60.1 (±12.4) years. PSS-QoL-dryness revealed significant negative correlations with Schirmer's test (r = −0.31, p < 0.05) and SSF-test (r = −0.390, p < 0.01). In contrast, we found no significant correlation between ESSPRI-dryness and any objective dryness test. Lower perceived dryness was associated with higher immunological activity determined by increased levels of IgG, FLC and RF-IgA. Whereas patients with only subjective signs of dryness had lower immunological activity.Discussion: Patients' perception of dryness assessed by PSS-QoL correlates with objective measurements of salivary gland function while ESSPRI-dryness did not. Based on the PSS-QoL and objective measures of dryness two distinct groups of PSS patients could be distinguished, which may have implications in daily practice and future clinical studies.

Fatigue in Saudi Patients with Primary Sjögren's Syndrome and Its Correlation with Disease Characteristics and Outcome Measures: A Cross-Sectional Study.

BackgroundFatigue is a prevalent symptom affecting primary Sjögren’s syndrome (pSS) patients. The purpose of this study is to determine the prevalence of fatigue in Saudi pSS patients and its correlation with disease features and outcome measures using a validated tool.MethodsThis is a cross-sectional study evaluating fatigue in pSS using the Arabic version of the fatigue severity scale (FSS). The EULAR Sjögren’s syndrome disease activity index (ESSDAI) and EULAR Sjögren’s syndrome patient reported index (ESSPRI) were calculated.ResultsForty-one patients met the sample criteria and were involved in the final report. There were predominantly females (78%) with a mean (±SD) age and disease duration of 58.76±12.7 and 4.6±2.28 years, respectively. Based on the FSS, 18 (43.9%) patients had a positive test with a mean score of 5.43±0.76. The mean ESSDAI was 9.95±7.73, while the mean EESPRI was 5.17±2.4 with individual component scores were dryness (5.23±2.62), fatigue (5.4±2.88), and pain (4.88±3.31). The FSS had a significant correlation with PGA (r=0.559; p<0.001), PhGA (r=0.671; p<0.001), ESSDAI (r=0.402; p=0.01), ESSPRI fatigue component (r=0.0.621; p<0.001), ESSPRI pain component (r=0.558; p<0.001), and missed significance for the ESSPRI dryness component (r=0.289; p=0.071). There was no correlation between the total ESSPRI score and presence of fatigue (r=−0.261; p=0.104) nor the FSS score (r=−0.136; p=0.409).ConclusionFatigue is prevalent in Saudi pSS patients. FSS correlated with ESSDAI and ESSPRI components but not its total score signaling other unmeasured factors contributing to fatigue development.

The reliability and validity of the European League Against Rheumatism Sjögren Syndrome Patient Reported Index in patients with primary Sjögren syndrome: A Turkish version study

Objectives This study aims to assess the reliability and validity of the Turkish version of the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI) (TR) in patients with primary Sjögren syndrome (pSS).Materials and methods A cross-sectional survey study design and analysis were used to assess the reliability and validity of the ESSPRI (TR) between March 2019 and July 2019. A total of 30 patients (5 males, 25 females; mean age 54.1±10.5 years; range, 18 to 75 years) diagnosed as pSS according to revised American College of Rheumatology (ACR)/EULAR classification criteria were included. ESSPRI (TR) was applied to the patients with face-to-face interviews twice: on their first visit and after an interval of 15 days. The test-retest reliability was assessed with the intraclass correlation coefficient (ICC), and the internal consistency of the multi-item subscales by calculating Cronbach alpha values. The correlations between basal and stimulated salivary flow (BSF and SSF), Oral Health Impact Profile-14 (OHIP-14) and Oral Health-Related Quality of Life-UK (OHRQOL-UK) questionnaires were evaluated to determine the construct validity.Results The ICC value for the test/retest reliability of ESSPRI (TR) was 0.925. The internal consistency was 0.682. There were low to moderate correlations between the ESSPRI (TR) total score and BSF (-0.39), SSF (-0.50), OHIP-14 total (0.57) and OHRQOL-UK total (-0.67).Conclusion The Turkish version of the ESSPRI was found to be clinically valid and reliable to be used in clinical evaluations and rehabilitation interventions in patients with pSS.

Research in Brief

RSLV-132, a biological drug consisting of an RNase–IgG1 Fc fusion protein, improved severe fatigue in patients with primary Sjögren's syndrome in a phase 2 randomised trial. James Posada and colleagues randomly assigned 30 patients (3:1) to receive 10 mg/kg intravenous RSLV-132 (n=22) or placebo (n=8) for 12 weeks. Patients in the RSLV-132 group achieved clinically meaningful improvements on the EULAR Sjögren's syndrome patient reported index (ESSPRI), FACIT fatigue, profile of fatigue, and the digit symbol substitution test, which correlated with increases in interferon-inducible gene expression (the primary outcome) via an unclear mechanism.

Iguratimod treatment reduces disease activity in early primary Sjögren's syndrome: An open-label pilot study

Objectives To evaluate the efficacy and safety of iguratimod in patients with early primary Sjögren's syndrome (pSS). Methods Twenty-seven disease-modifying antirheumatic drug-naive female patients met the revised American-European Consensus Group criteria for pSS were enrolled in this open-label pilot study. Patients were treated with iguratimod 25 mg twice a day for 24 weeks. The disease activity was assessed with European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at 12 and 24 weeks. Salivary and lacrimal gland function, laboratory, and subjective variables were also assessed. Generalized estimating equations were used to analyze parameters over time. Results ESSDAI (median, 5 versus 2 versus 2, p < .01), IgG (median, 26.6 versus 22.4 versus 21.4 g/L, p < .01) and rheumatoid factor (median, 119.9 versus 94.1 versus 83.8 lU/mL, p < .01) levels decreased significantly during iguratimod treatment. ESSPRI, salivary and lacrimal gland function, fatigue and health-related quality of life did not change during treatment. One patient experienced thrombocytopenia, and no other serious adverse effects were observed. Conclusion In this study, iguratimod treatment is safe and effective for improving disease activity and laboratory parameters in early pSS patients.

The efficacy and mechanism for action of iguratimod in primary Sjögren's syndrome patients.

Primary Sjögren's syndrome (pSS) has been proven as a systemic autoimmune disorder (such as Sjogren's syndrome dry eye). This research aimed to evaluate potential treating effects of Iguratimod on pSS. Fifty pSS patients were enrolled and randomly divided into Conventional group and Iguratimod group. Improvement in pSS was evaluated every 4weeks. pSS disease activity was evaluated with European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI). Symptoms were evaluated by determining EULAR Sjögren's syndrome patient-reported index (ESSPRI), platelet (PLT), IgG and Schirmer I test. Peripheral blood B cell molecules (CD135, IgD, CD38, CD20) and human B cell-activating factor-receptor (BAFF-R) were analyzed with flow cytometry. After treating for 12-weeks, pSS patients in Iguratimod and Conventional group showed a significant decrease in disease activity (ESSPRI, ESSDAI, PLT, IgG and Schirmer I test) comparing with baselines. Patients' ESSPRI (2.92 ± 0.19) and disease activity of ESSDAI (4.32 ± 0.29), PLT (95.64 ± 1.86), IgG (13.0 ± 0.45) and Schirmer I test (4.67 ± 0.31) in Iguratimod group were significantly lower compared to Conventional group (4.64 ± 0.15, 5.8 ± 2.08, 77.44 ± 1.41, 16.5 ± 0.44 and 2.25 ± 0.11) (p < 0.0001). Changes of ESSPRI, ESSDAI, PLT, IgG and Schirmer I test were remarkable observed between two groups (p < 0.001). Iguratimod and Conventional treatment demonstrated a significant reduction in total B cells in pSS patients compared with pre-treatment. The pSS patients from Iguratimod and Conventional group showed a significant decreased BAFF-R (61.82 ± 1.52, 74.07 ± 1.11) and CD38+IgD+ (48.08 ± 0.92, 62.66 ± 1.12) on B cells after treatment compared with baseline (92.26 ± 0.32, 91.53 ± 0.45, 84.39 ± 0.59, 85.04 ± 0.46) (p < 0.001). After treating 12 weeks, BAFF-R, CD38+IgD+ expression in Iguratimod group decreased significantly compared to Conventional group (p < 0.001). Iguratimod alleviated symptoms and mediated adaptive-immunity balance by suppressing BAFF-R positive B cell in pSS patients.

OP0302 IANALUMAB (VAY736), A DUAL MODE OF ACTION BIOLOGIC COMBINING BAFF RECEPTOR INHIBITION WITH B CELL DEPLETION, REACHES PRIMARY ENDPOINT FOR TREATMENT OF PRIMARY SJOGREN’S SYNDROME

Background:Primary Sjogren’s syndrome (pSS) is a multi-organ autoimmune disease mainly affecting excretory glands and characterised by B-cell hyperactivity. No approved systemic treatment is available. Ianalumab (VAY736) is an anti-B-cell activating factor (BAFF) receptor fully human monoclonal antibody, engineered for direct ADCC-mediated B-cell depletion.Objectives:This phase 2b study aimed at establishing a dose-response relationship over a range of VAY736 doses, using change from baseline (BL) in EULAR Sjogren’s Syndrome Disease Activity index (ESSDAI) over 24 Weeks (Wks) as primary endpoint. The study is ongoing with a second blinded treatment period up to Wk52. Here we report efficacy and safety Wk24.Methods:190 patients (pts) were randomised 1:1:1:1 to receive monthly s.c. doses of VAY736 (5, 50, 300mg) or placebo (PBO). Prior to 1st-dose of study treatment, pts received methylprednisolone i.v. 250mg. Eligible pts fulfilled American European Consensus Group (AECG) criteria, were anti-Ro/SSA+, had ESSDAI ≥6 and EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI) ≥5. Statistical methods included MCP-Mod to assess dose-response on change of ESSDAI from BL and responder rate analysis to calculate the proportion of pts with ≥3 points improvement on ESSDAI. Secondary endpoints included ESSPRI, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), Physician’s (PhGA) and Patient’s Global Assessments (PaGA), SF-36, stimulated salivary flow (sSF), Schirmer’s test.Results:Primary endpoint was met with statistically significant dose-response for ESSDAI (Figure). The largest ESSDAI reduction was 1.92 points over PBO for VAY736 300mg at Wk24. Responder rate analysis on ESSDAI revealed for 300mg vs PBO responder rates of 42/47 (89.4%) vs 30/49 (61.2%), a difference of 28.1% (p=0.0019). No differences were seen for 5mg and 50mg vs PBO. PhGA change from BL was significantly different between 300mg and PBO (p=0.022). A numerical trend for sSF improvement for VAY736 300mg compared to PBO was notable at Wk24 (p=0.092). For secondary endpoints ESSPRI and FACIT-F, VAY736 treatment showed no benefits over PBO. PBO responses were generally high. Incidence of treatment emergent AEs was comparable across all studied groups, whereby site injection reactions were most frequent, mostly mild and showed a dose-response.Conclusion:Primary endpoint assessing ESSDAI was met, showing statistically significant dose-response for ianalumab with clinically important improvement for 300mg vs PBO. Preliminary safety profile of ianalumab was good.Figure.ESSDAI Change from Baseline over Time up to Week 24 Reveals a Statistically Significant Dose Response RelationshipDisclosure of Interests:Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Robert Fox Consultant of: Novartis, Pfizer and Lilly, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Athena Papas Grant/research support from: Novartis, Consultant of: Novartis, Thomas Grader-Beck Grant/research support from: Abbvie, Celgene, Consultant of: Novartis, Lilly, Ben A Fisher Consultant of: Novartis, Roche, BMS and Servier, Filipe Barcelos Consultant of: Pfizer and Lilly, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc, Robert J Moots: None declared, Guido Junge Shareholder of: Novartis, Employee of: Novartis, Janice Woznicki Shareholder of: Novartis, Employee of: Novartis, Monika Sopala Shareholder of: Novartis, Employee of: Novartis, Wen-Lin Luo Shareholder of: Novartis, Employee of: Novartis, Wolfgang Hueber Shareholder of: Novartis, Employee of: Novartis

Correlation of sleep quality with fatigue and disease activity among patients with primary Sjögren's syndrome: a cross-sectional study.

Fatigue is a frequent symptom in patients with primary Sjögren's syndrome (pSS) and can be a cause of or be associated with sleep disorders. To assess the sleep quality of pSS patients and its relationship with fatigue and disease activity. Analytical observational study conducted at an exercise psychobiology laboratory. Sleep quality was evaluated using the Pittsburg sleep quality index (PSQI) and actigraphy. Fatigue was evaluated through the Profile of Fatigue and Discomfort - Sicca Symptoms Inventory (PROFAD-SSI-SF) and a visual analogue scale for fatigue (VAS-fatigue). Disease activity was evaluated using a visual analogue scale for pain (VAS-pain), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Disease Activity Index (ESSDAI). We summarized the data through descriptive statistics. A total of 50 female patients with pSS, of average age 56.4 years, were included in the study; 80% presented low disease activity. The total PSQI score showed that 74% had poor sleep. The actigraphy showed mean sleep latency of 26.2 minutes and mean nightly awakening of 48.2 minutes (duration of wakings after sleep onset, WASO). There were correlations between PSQI and VAS-pain, VAS-fatigue, PROFAD-SSI and ESSPRI. Actigraphy showed a correlation between the duration of WASO and ESSDAI. The present study provides important information regarding correlations between sleep disorders and disease activity. There is a need for proper control over disease activity and for development of strategies to help patients to sleep better in order to diminish their fatigue.