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Objective: Systemic features influence disease prognosis and choice of treatment in primary Sjogren's syndrome (pSS). Our aim was to investigate the prevalence of pulmonary involvement in pSS patients and to classify patients according to the pulmonary domain of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). Methods: This retrospective cohort study included consecutive pSS patients, fulfilling American-European Consensus Group/American College of Rheumatology classification criteria, who visited the Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, in 2015. Data on pulmonary complaints and pulmonary tests were obtained from electronic patient records. Pulmonary involvement was recorded if therapy was needed or follow-up was recommended, and when it was possibly or assumed to be related to pSS instead of coincidental factors. Results: Of the 262 included pSS patients, 88 (34%) had pulmonary complaints, mostly cough or dyspnoea on exertion. Pulmonary diagnostics were performed in 225 patients (86%). Pulmonary involvement was present and assumed to be related to pSS in 25 patients (10%) and possibly related to pSS in 14 (5%). Interstitial lung disease (ILD, n = 15), especially non-specific interstitial pneumonia (n = 7), was present most commonly. In total, 16 patients (6%) were scored as low (n = 4), moderate (n = 11), or high activity (n = 1) on the ESSDAI pulmonary domain. Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was present in 10-15% of pSS patients, of which ILD was most common. Of all pSS patients, 6% were scored as active on the pulmonary domain of the ESSDAI.

BackgroundPrimary Sjögren’s syndrome (pSS) has great impact on all aspects of patients’ lives, not only physically, but also mentally, socially and financially.1 Sicca symptoms are mainly treated with local treatment, but no systemic immunosuppressive treatment is registered yet for pSS, which may have significant consequences on whether patients find their symptom state acceptable (PASS). In a previous study, a cut-off for acceptable symptom state based on the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI, score 2ObjectivesTo explore the presence of PASS in a standard of care cohort of pSS patients and to compare patient characteristics and disease activity including ESSPRI between patients with and without PASS.MethodsConsecutive outpatients with pSS from the REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort, who fulfilled the ACR/EULAR classification criteria and had available PASS data at baseline were included. Patient-reported outcomes were reported through questionnaires, which included the PASS (“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/no) and ESSPRI (“How severe has your dryness, fatigue and pain been during the last two weeks?”; scale 0-10). An acceptable ESSPRI symptom state has been defined as 2 Systemic disease activity was assessed with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). Independent samples t-test, Mann-Whitney U test or Chi Square test were used to analyse differences between patients with or without PASS.ResultsOf 277 included pSS patients, 248 (90%) were female, median age was 54 years (IQR 43-64) and disease duration 5 years (2-11). 198 (71%) patients scored their symptom state as acceptable according to PASS. Patients with PASS were significantly older and had a longer disease duration compared to patients without PASS. Furthermore, patients with PASS had more often a low disease activity according to ESSDAI, and less often moderate disease activity (Table 1). The difference in ESSDAI activity was mainly observed in the articular and constitutional domains. ESSPRI was significantly lower in patients with PASS (median 5 vs. 7). No differences were seen in functional or laboratory parameters (Table 1). Of all included patients, only 86 (31%) patients had an acceptable symptom state according to the pre-defined cut-off point for ESSPRI (score Table 1.Baseline characteristics of pSS patients with and without PASSPASS (n=198)Without PASS (n=79)Gender (female)177 (89)71 (90)Age (years)57 (44-65)*49 (41-60)*Disease duration (years)6 (2-12)*5 (2-8)*ESSDAI (total)4 (2-6) (n=191)4 (2-9) (n=75)127 (66)*38 (51)*5-1452 (27)*32 (43)*≥1412 (6)5 (7)ESSPRI (total)5 (4-7)**7 (6-8)**80 (40)**6 (8)**Schirmer’s test (mm)4 (1-10) (n=179)4 (1-10) (n=72)Ocular staining score2 (1-4) (n=190)2 (0-4) (n=77)Unstimulated whole salivary flow (ml/min)0.05 (0.01-0.14) (n=187)0.08 (0.01-0.19) (n=76)Stimulated whole salivary flow (ml/min)0.54 (0.15-0.99) (n=189)0.58 (0.21-0.97) (n=76)SSA positive172/197 (87)66/79 (84)IgG (g/L)14 (11-19) (n=196)14 (10-19) (n=79)Rheumatoid factor (IU/ml)12 (3-39) (n=196)16 (2-47) (n=78)Data presented as median (IQR) or n (%)*Significant difference p***Significant difference pConclusionThe majority (71%) of pSS patients reported being in an acceptable symptom state according to the PASS question in our standard of care cohort in daily clinical practice, despite high ESSPRI scores (60% with score ≥5). Further analyses of influences of treatment in these patients will be conducted.References[1]Vieira et al. Clin Exp Rheum 2021;39(Suppl. 133):S14-S16.[2]Seror et al. Ann Rheum Dis 2016;75:382-389.AcknowledgementsUnrestricted grants from the Dutch Arthritis Patients Association (ReumaNL), Bristol-Myers Squibb and NovartisDisclosure of InterestsLiseth de Wolff: None declared, Suzanne Arends: None declared, Esther Mossel: None declared, Greetje S. van Zuiden: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Lisette Olie: None declared, Alja J. Stel: None declared, Konstantina Delli: None declared, Gwenny M. Verstappen: None declared, Frans G.M. Kroese: None declared, Arjan Vissink: None declared, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche

Background:Defining a primary study endpoint that is able to discriminate between active treatment and placebo is crucial for clinical trials in primary Sjögren syndrome (pSS). Recent trials used the validated ESSDAI as primary endpoint, but found large ‘response rates’ in the placebo group too. Since pSS is a very heterogenous disease, a composite endpoint including multiple aspects (i.e., systemic, patient-reported, functional and biological) may be more appropriate to demonstrate clinical efficacy.Objectives:To develop a composite endpoint for pSS based on expert opinion and analysis of trial data.Methods:Based on expert opinion, 5 items were found to be most relevant to assess the effect of treatment in pSS patients: ESSDAI, ESSPRI, OSS, SWS and RF/IgG (Figure 1). These items were tested using data at week 24 of the randomized, double blind, placebo-controlled ASAP-III trial.1ROC analysis was used to assess the discrimination of effect between the abatacept (n=40) and placebo (n=39) treatment groups. The optimal cut-off point per item was defined by the highest sum of sensitivity and specificity. The percentage of patients responding to the individual items (Figure 1) and the composite endpoint (named CRESS) was calculated.Results:For ESSDAI, ROC analysis showed that both absolute and relative change in ESSDAI were not able to discriminate between treatment groups (AUC 0.536 and 0.559) and no optimal cut-off point could be identified. According to an in SLE developed endpoint and based on expert opinion, it was decided to aim for the validated definition of low disease activity (ESSDAI2.For ESSPRI, ROC analysis (AUC 0.629) showed an optimal cut-off point of -13.8%. Therefore, the validated definition of ESSPRI response (≥-15% or 1 point)2was used. For OSS and SWS, ROC analysis (AUC 0.555 for OSS>3 at baseline and AUC 0.556 for SWS>0 at baseline) could not identify an optimal cut-off point, so the definitions based on expert opinion were kept (Figure 1).For serological items, ROC analysis (AUC 0.861 for RF>0 at baseline and 0.615 for IgG) showed optimal cut-off points of -23% and -2.2%, respectively. It was decided to round these numbers to ≥25% decrease in RF or ≥5% decrease in IgG. Responding to ≥3 of the 5 items discriminated best between the abatacept and placebo groups. The final response rate to our composite endpoint (CRESS responders) was 55% vs. 13% in the abatacept and placebo groups, respectively (PConclusion:This concept of the new ‘Composite of Relevant Endpoints for Sjögren’s Syndrome’ (CRESS) is developed. With this composite endpoint, it is possible to discriminate between abatacept and placebo response in pSS patients. Additional validation analyses in independent, global, multi-center, placebo-controlled trials of biological DMARDs in pSS and NECESSITY will be performed.References:[1]van Nimwegen et al. Lancet Rheumatol.Published online 31-01-2020.[2]Seror et al. Ann Rheum Dis. 2016;75(2):382-9.Acknowledgments:The authors would like to thank Raphaele Seror for initial discussions on potential components and criteria to be explored in the creation of a composite pSS endpoint. The authors would also like to acknowledge valuable discussions with Marleen Nys, Miroslawa Nowak, Dennis Grasela, Antoine Sreih and Subhashis Banerjee.Disclosure of Interests:Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Jolien F. van Nimwegen Consultant of: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Gwenny M. Verstappen: None declared, Arjan Vissink: None declared, Neelanjana Ray Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Frans G.M. Kroese Grant/research support from: Unrestricted grant from Bristol-Myers Squibb, Consultant of: Consultant for Bristol-Myers Squibb, Speakers bureau: Speaker for Bristol-Myers Squibb, Roche and Janssen-Cilag, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant of: Consultant for Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Speaker for Bristol-Myers Squibb and Novartis.

Background:Several large randomised controlled trials (RCTs) in primary Sjögren’s syndrome (pSS) failed to demonstrate drug efficacy.1-4 Many of these trials used ESSDAI as primary endpoint, showing large but similar response rates in active treatment and placebo groups.1,3,4 Given the heterogeneous nature of pSS, there is need for a composite endpoint including multiple clinically relevant parameters.Objectives:To develop and validate the Composite of Relevant Endpoints in Sjögren’s Syndrome (CRESS).Methods:A multidisciplinary team of pSS experts selected clinically relevant items and measurements to include in the CRESS. Definition of response of CRESS items was based on clinical relevance, previously defined minimal clinically important improvement (MCII) and data of the single-centre ASAP-III (abatacept) trial.1 CRESS was validated in three independent RCTs: TRACTISS (rituximab) trial2, multi-centre abatacept trial3 and ETAP (tocilizumab) trial4. CRESS response rates were assessed at the primary endpoint visit of all four trials.Results:Five complementary items were selected to form CRESS: systemic disease activity, patient-reported symptoms, tear gland, salivary gland and serological item. Definition of response per item is presented in Table 1. Total CRESS response was defined as response on ≥3 of 5 items. Since not all trials have ocular staining score or salivary gland ultrasonography (SGUS) available, the concise CRESS (cCRESS) was developed simultaneously, leaving Schirmer’s test and unstimulated whole saliva flow for the tear and salivary gland items, respectively. In the ASAP-III trial, CRESS response rates were 24/40 (60%) for abatacept vs. 7/39 (18%) for placebo at week 24 (pTable 1.CRESS items and definition of responseItemsMeasurementsDefinition of responseSystemic disease activityClinESSDAIScorePatient-reported symptomsESSPRIDecrease of ≥1 point or ≥15%Tear gland*Schirmer/OSS**-If abnormal Schirmer (≤5 mm) at baseline: increase of ≥5 mm in Schirmer-Or if abnormal OSS (≥3 points) at baseline: decrease ≥2 points in OSS-Or if both Schirmer/OSS normal scores at baseline: no change to abnormal in bothSalivary gland*UWS/SGUSIncrease of ≥25% in UWS (or if score is 0 at baseline, any increase)Or decrease of ≥25% in total Hocevar score (SGUS)SerologicalRF/IgGDecrease of ≥25% in RFOr decrease of ≥10% in IgGCRESS responderResponder on ≥3 of 5 itemsOcular Staining Score (OSS), Unstimulated whole salivary flow (UWS), Salivary gland ultrasonography (SGUS), Rheumatoid factor (RF), Immunoglobuline G (IgG)*Concise CRESS (cCRESS): CRESS without OSS and SGUS, leaving Schirmer and UWS for tear and salivary gland items, respectively**Mean of both eyesIn the external validation trials, cCRESS response rates for TRACTISS were: 33/67 (49%) rituximab vs. 20/66 (30%) placebo at week 48 (p=0.026). CRESS response rates (without SGUS) for the multi-centre abatacept trial were: 41/92 (45%) abatacept vs. 30/95 (32%) placebo at week 24 (p=0.067). cCRESS response rates (without rheumatoid factor) for ETAP were: 10/55 (18%) tocilizumab vs. 13/55 (24%) placebo at week 24 (p=0.482) (Figure 1A-D). Compared to ESSDAI MCII of ≥3 points decrease, CRESS was able to approximately halve placebo response rates in RCTs with high baseline ESSDAI scores (>5) (Figures 1E-H).Conclusion:CRESS shows lower placebo response rates compared to ESSDAI MCII, which is crucial for demonstrating treatment efficacy. With the CRESS, higher response rates in abatacept and rituximab treated patients compared to placebo were found in RCTs which previously showed negative primary endpoint results. CRESS confirmed that no differences were found for almost all outcome measures between tocilizumab and placebo,4 with low response rates. The CRESS is a well-balanced, feasible, composite endpoint for use in clinical trials in pSS patients.References:[1]Van Nimwegen 2020;9913(19):1–11[2]Bowman 2017;69(7):1440–50[3]Baer (doi:218599)[4]Felten (doi:21846)Acknowledgements:The authors would like to acknowledge all contributors of the included trials.Disclosure of Interests:Suzanne Arends: None declared, Liseth de Wolff: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol Myers Squibb, Consultant of: Bristol Myers Squibb, Gwenny M. Verstappen: None declared, Jelle Vehof: None declared, Michele Bombardieri Consultant of: MedImmune, GlaxoSmithKline, Grant/research support from: MedImmune, Simon J. Bowman Consultant of: AstraZenecea/MedImmune, Bristol Myers Squibb, Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MTPharma, Novartis, Ono, Pfizer, Takeda, UCB, XTLBio, Elena Pontarini: None declared, Alan Baer Consultant of: Bristol Myers Squibb, Sanofi, VielaBio, Novartis, Marleen Nys Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Jacques-Eric Gottenberg Grant/research support from: Bristol Myers Squibb, Pfizer, Renaud FELTEN: None declared, Neelanjana Ray Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Arjan Vissink: None declared, Frans G.M. Kroese Speakers bureau: Bristol Myers Squibb, Roche and Janssen-Cilag, Consultant of: Bristol Myers Squibb, Grant/research support from: Unrestricted grants from Bristol Myers Squibb, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche

Background:Abatacept (CTLA-4-Ig) targets the CD80/CD86:CD28 co-stimulatory pathway required for full T-cell activation and T-cell dependent activation of B-cells. The Abatacept Sjögren Active Patients phase III (ASAPIII) trial is a mono-center, investigator-initiated, placebo controlled study with an open-label extension phase (NCT02067910), which assessed the efficacy and safety of weekly subcutaneous abatacept (125mg) in patients with early active primary Sjögren’s syndrome (pSS). Previous analyses of the double blind phase showed no significant effect of abatacept treatment compared to placebo on the primary endpoint, difference in EULAR Sjögren’s syndrome disease activity index (ESSDAI) at week 24.1Objectives:To evaluate the efficacy and safety of extended (48 weeks) open label abatacept treatment in pSS patients.Methods:Included patients had biopsy-proven pSS, fulfilled the AECG and ACR-EULAR criteria, had disease duration ≤7 years (median 2 years), ESSDAI ≥5, and 89% were anti–SSA positive. All 40 patients who received abatacept (ABA) in week 0-24 were subsequently treated with abatacept from week 24-48. Of the 40 patients who received placebo (PLB) in week 0-24, 2 were lost to follow up, and 38 were treated with abatacept from week 24-48. Systemic disease activity (ESSDAI), patient reported symptoms (ESSPRI), serological outcomes (RF and IgG), ocular staining score (OSS) and unstimulated whole salivary flow (UWS) were assessed. We evaluated whether outcomes improved within treatment groups, from week 0 to subsequent visits and from week 24 to subsequent visits:1.Within ABA→ABA treated patients:a. Week 0-48 to assess overall efficacy.b. Week 24-48 to assess additional efficacy of long term treatment.2.Within PLB→ABA treated patients:a. Week 0-24 to assess whether a placebo effect occurred.b. Week 24-48 to assess short-term efficacy of open label ABA.GEE modeling was used to test significance of changes over time. Missing data were not imputed.Results:ESSDAI and ESSPRI were improved within ABA/ABA patients between week 0-48 with additional efficacy after week 24, and within PLB/ABA patients after switching to ABA. Significant decreases in ESSDAI and ESSPRI were also seen within PLB treated patients between week 0-24 (Figure 1). IgG and RF were improved within ABA/ABA patients between week 0-48 with additional efficacy after week 24, and within PLB/ABA patients after switching to ABA. OSS was improved within ABA/ABA treated patients between week 0-48. UWS only showed significant improvement in week 36 within ABA/ABA treated patients. No changes in IgG, RF, OSS or UWS were seen within PLB treated patients. No deaths occurred. One serious adverse event possibly related to intervention occurred during ABA treatment.Conclusion:ESSDAI and ESSPRI improved significantly during 48-week treatment with abatacept. Placebo treated patients also showed significant improvement in both indices and further improvement occurred after switching to abatacept. Biological activity was decreased by abatacept treatment. 48-week abatacept treatment improved OSS, and might improve UWS. Abatacept was well tolerated by pSS patients.References:[1]van Nimwegen et al. Lancet Rheumatol.Published online 31-01-2020Acknowledgments:This study was funded by Bristol-Myers Squibb. We thank all patients for participation in the ASAP-III trial.Disclosure of Interests:Suzanne Arends Grant/research support from: Grant/research support from Pfizer, Jolien F. van Nimwegen Consultant of: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Esther Mossel: None declared, Greetje S. van Zuiden Speakers bureau: Roche, Konstantina Delli: None declared, Alja J. Stel: None declared, Bert van der Vegt Consultant of: Advisory board member for Philips and Visiopharm., Erlin A. Haacke: None declared, Lisette Olie: None declared, Leoni Los: None declared, Gwenny M. Verstappen: None declared, Sarah A. Pringle: None declared, Fred K.L. Spijkervet: None declared, Frans G.M. Kroese Grant/research support from: Unrestricted grant from Bristol-Myers Squibb, Consultant of: Consultant for Bristol-Myers Squibb, Speakers bureau: Speaker for Bristol-Myers Squibb, Roche and Janssen-Cilag, Arjan Vissink: None declared, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant of: Consultant for Bristol-Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Speaker for Bristol-Myers Squibb and Novartis.

Background The major histopathological finding in salivary glands of primary Sjogren’s syndrome (pSS) patients are periductal lymphocytic infiltrates (foci). In association with these infiltrates, lymphoepithelial lesions (LELs) may be formed. LELs are defined by infiltration of lymphocytes within the epithelium with hyperplasia of ductal cells. Although it has been suggested that B-lymphocytes predominate in LELs, the relative role of B- and T-lymphocytes in LEL formation is not known. Since LELs are a characteristic finding in salivary glands of pSS patients, quantification of B- and T-lymphocytes in the different stages of LEL development will give more insight in their formation as well as in the pathogenesis of pSS. Objectives To quantify the numbers of B- and T-lymphocytes in different stages of LEL development in parotid and labial gland biopsies of pSS patients. Methods The study population consisted of 15 pSS patients, who fulfilled the ACR-EULAR criteria and underwent salivary gland biopsies of both the parotid and labial gland. Patients were not treated with biologicals and 13 patients were not using other immunosuppressive therapy. Presence and severity of LELs were evaluated on HE stained sections. Severity of lesions was scored from stage 0 to stage 3 (stage 0: lymphocytic ductal infiltration without hyperplasia of the epithelium; stage 1: lymphocytic ductal infiltration and Results B- and T-lymphocytes can both infiltrate within the ductal epithelium forming LELs in salivary glands of pSS patients. T-lymphocytes were present in all LELs, scattered through the whole ductal epithelium. Whereas B-lymphocytes were found in clusters, mostly located in the hyperplastic area of the ductal epithelium. With higher severity of LELs, the numbers of B- and T-lymphocytes increased significantly, in both the parotid and labial gland. The numbers of B-lymphocytes increased relatively more with higher severity of LELs than T-lymphocytes. This has led to an increased intraepithelial B/T ratio in more pronounced LELs. This increased B/T ratio was even more pronounced in parotid than in labial glands. In both glands, there was a predominance of T-lymphocytes in lower LEL stages. In more severe LEL stages, B-lymphocytes outnumbered the T-lymphocytes. Conclusions Given the relative increase in the number of B-lymphocytes with higher severity of LELs as well as their close association with proliferating ductal epithelial cells, we conclude that B-lymphocytes play a major role in the hyperplasia of the ductal epithelium. Disclosure of Interest None declared

Background Salivary gland ultrasound (SGUS) is cheap, non-invasive and easy to perform in an outpatient setting. The ACR-EULAR criteria were recently developed to reach international consensus regarding the classification of primary Sjogren’s syndrome (pSS), but SGUS is not yet included as a classification item. Objectives To assess the performance of the ACR-EULAR criteria when salivary gland ultrasound (SGUS) replaces current items, in a large cohort of patients clinically suspected or diagnosed with pSS in daily clinical practice. Methods Included were all consecutive outpatients who underwent SGUS between October 2014 and , July 2017 and had a complete data-set on all ACR-EULAR items. Classification according to the criteria was determined separately in patients who were subjected to a labial or parotid gland biopsy. For SGUS, the average score for hypoechogenic areas in the parotid and submandibular glands on one side was applied (range 0–3)1. The optimal cut-off value for our SGUS score was determined using ROC analysis. Clinical diagnosis by the treating physician was used as gold standard. Area under the curve (AUC), absolute agreement, sensitivity and specificity of the original and adjusted ACR-EULAR criteria sets were determined. Results Of the 363 consecutive patients, 243 patients had a complete data-set, of whom 147 patients were diagnosed with pSS. Accuracy of SGUS to predict clinical diagnosis was good, with an AUC of 0.860 and optimal cut-off value of ≥1.5. When applying a weight of 1 point for a positive SGUS, the cut-off value of the ACR-EULAR criteria to discriminate between pSS and non-pSS remained 4, irrespective of the type of biopsy used. In patients who underwent a labial gland biopsy (n=124), the original ACR-EULAR criteria showed an AUC of 0.965 (figure 1A). Absolute agreement with clinical diagnosis was 94.4%, sensitivity was 95.9% and specificity was 92.2%. When SGUS replaced the labial gland biopsy, absolute agreement was 87.9%, sensitivity was 82.2% and specificity was 96.1%. When SGUS replaced anti-SSA antibody status, absolute agreement was 89.5%, sensitivity was 86.3% and specificity was 94.1%. When SGUS replaced the ocular staining score (OSS), Schirmer’s test or unstimulated whole saliva flow (UWS), absolute agreement varied between 89.5%–93.5%, sensitivity varied between 90.4%–95.9% and specificity varied between 88.2%–92.2%. In patients who underwent a parotid gland biopsy (n=198), similar results were found (figure 1B). Conclusions SGUS cannot be used as a replacement for salivary gland biopsy or anti-SSA antibody status in the ACR-EULAR criteria because of a substantial reduction in sensitivity. For diagnostic purposes, a high sensitivity is preferred over a high specificity. Replacement of the OSS, Schirmer’s test or UWS by SGUS only resulted in negligible changes in accuracy of the ACR-EULAR criteria. With SGUS being able to replace one of these function tests, clinicians are offered more options that could lead to fulfilment of the ACR-EULAR criteria. Reference [1] Mossel, et al. Ann Rheum Dis2017: Published online first at December 12. Disclosure of Interest None declared

Background Ultrasound of the major salivary glands (SGUS) has shown high diagnostic accuracy for primary Sjogren9s syndrome (pSS) [1,2]. None of the existing studies, however, included a control group of patients with sarcoidosis, amyloidosis, human immunodeficiency virus (HIV) or hepatitis C (HCV) infection [2]. These diseases are known to frequently affect the major salivary glands, cause dry mouth or may have histopathology similar to pSS. Objectives To assess the diagnostic accuracy of SGUS to differentiate pSS from systemic diseases with salivary gland involvement. Methods Twenty consecutive patients fulfilling the AECG criteria for pSS and 20 consecutive patients with well-established systemic diseases, i.e., 5 patients with sarcoidosis, 5 patients with amyloidosis, 5 patients with HIV infection and 5 patients with HCV infection, were included. Echogenicity, parenchymal homogeneity, presence of hypoechogenic areas and clearness of posterior glandular border of both parotid and submandibular salivary glands were scored independently by two blinded observers and rated according to the Hocevar et al scoring system (ultrasound total score (UTS), range: 0–48) [3]. The optimal cut-off point was determined by using ROC curve. The agreement between SGUS positivity and classification as pSS was assessed. Results The median age of patients with pSS and systemic diseases was 50 and 53 years, respectively. Daily complaints of dry mouth longer than 3 months, need of liquid to swallow food and recurrent or persistent swelling of the major salivary glands were reported by 95%, 85% and 70% of patients with pSS compared to 45%, 30% and 20% of patients with systemic diseases. The accuracy of SGUS to discriminate pSS was excellent, with an area under ROC of 0.91 and optimal cut off point of 15. The agreement between SGUS and diagnosis for pSS was good (κ=0.75, percentage of absolute agreement 87.5) with a sensitivity of 90%, specificity of 85%, positive predictive value of 86%, negative predictive value of 89% and diagnostic odds ratio of 51. UTS was positive in 2 patients with HIV infection and one patient with sarcoidosis. Patients with pSS had significantly higher UTS than patients with systemic diseases (median UTS 27 vs. 10, p Conclusions This pilot study indicates that SGUS has a high diagnostic accuracy to discriminate pSS from associated systemic diseases with salivary gland involvement. A minority of HIV and sarcoidosis patients, however, may show SGUS findings mimicking pSS. References Jousse-Joulin et al. Rheumatology (Oxford) 2016;55:789–800. Delli et al. Oral Dis 2015;21:792–800. Hocevar et al. Rheumatology (Oxford) 2005;44:768–72. Disclosure of Interest None declared

Background Ultrasound of major salivary glands (sUS) is an upcoming diagnostic method to assess the involvement of major salivary glands in primary Sjogren9s syndrome (pSS). In the AECG, ACR and recently published ACR-EULAR criteria, a positive salivary gland biopsy and/or presence of anti-SSA antibodies are necessary to classify a patient as pSS, while sUS is not included as a diagnostic item. Objectives To assess whether combining anti-SSA antibody status with sUS outcome can predict classification of patients as pSS in our inception cohort study. Methods Consecutive outpatients clinically suspected with pSS underwent sUS of the parotid and submandibular glands. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and clearness of salivary gland border were scored according to the Hocevar scoring system (total score 0–48). 1 Positive sUS was defined as total score ≥15. Patients underwent a diagnostic work up according to the AECG, ACR and ACR-EULAR criteria. We analyzed the predictive value of the combination of anti-SSA antibody status and sUS outcome for classification as pSS or non-pSS. Separate analyses were done considering either i) parotid gland biopsy or ii) labial gland biopsy as an item, when applying these classification criteria. Results Anti-SSA antibody status was positive in 53 (51%) patients and sUS was positive in 40 (39%) patients. When parotid gland biopsy outcome was considered as an item of the criteria, 45 of 97 patients were classified as pSS according to the AECG, 44 of 97 according to the ACR and 52 of 99 according to the ACR-EULAR criteria. The combination of presence of anti-SSA antibodies with positive sUS showed a very high positive predictive value for classification as pSS (94–97%) and the combination of absence of anti-SSA antibodies with negative sUS highly excludes classification (negative predictive value 98–100%). When labial gland biopsy outcome was considered as an item of the criteria, 49 of 96 patients were classified as pSS according to the AECG, 43 of 93 according to the ACR and 55 of 97 according to the ACR-EULAR criteria. The combination of presence of anti-SSA antibodies with positive sUS showed a high positive predictive value for classification as pSS (94–97%). However, the combination of absence of anti-SSA antibodies with negative sUS did not per se exclude classification (negative predictive value 89–93%). Conclusions In our prospective inception cohort study derived from daily clinical practice, the combination of presence of anti-SSA antibodies and positive sUS outcome highly predicts classification as pSS according to the AECG, ACR and ACR-EULAR classification criteria. References Hocevar et al. Rheumatology (Oxford) 2005;44:768–72. Disclosure of Interest None declared

Background Primary Sjogren9s syndrome (pSS) is a chronic and disabling disease, characterized by sicca symptoms of the eyes and mouth as well as fatigue. Besides these well-known symptoms, multiple studies have shown that women with pSS often experience complaints of vaginal dryness and dyspareunia. Objectives To compare sexual functioning and sexual distress between women with pSS and healthy controls, and to identify parameters that predict sexual dysfunctioning in women with pSS. Methods 46 women with pSS according to the AECG criteria (mean age 46.3±10.5) and 43 age-matched healthy controls (mean age 44.4±11.3) were included. Median disease duration of the patients was 7 years (interquartile range 4-14). Participants completed a self-administered questionnaire, which included the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), RAND-36 item health survey (RAND-36), Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Index (MFI) and Maudsley Marital Questionnaire (MMQ). In patients, disease activity was recorded with the EULAR Sjogren9s Syndrome Patient Reported Index (ESSPRI) and EULAR Sjogren9s Disease Activity Index (ESSDAI). Results Women with pSS had a significantly lower FSFI total score compared to healthy controls (median 20.6 vs. 30.3, p Sexual dysfunctioning correlated significantly with depressive symptoms (HADS), higher ESSPRI score, more symptoms of fatigue (MFI), lower mental quality of life (RAND-36) and relationship dissatisfaction (MMQ). Furthermore, sexual dysfunctioning correlated significantly with higher ESSDAI score only in premenopausal patients. Conclusions Sexual dysfunctioning is an important symptom and leads to psychological distress in women with pSS. Symptoms of depression and higher disease activity are associated with sexual dysfunctioning. When treating pSS, this aspect of the disease should not be overlooked. More research is needed to obtain knowledge on the pathogenesis of vaginal sicca symptoms in pSS and the best treatment for this complaint. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1871