Abatacept use for 24 weeks has a limited effect on salivary gland inflammation in Sjögren's disease patients.

Objectives: This study aimed to assess (1) effects of abatacept on salivary gland histology of Sjögren's disease (SjD) patients, (2) the predictive value of salivary gland histopathological characteristics at baseline for clinical response to abatacept treatment.

Methods: Patients (n=41) who participated in the Dutch ASAP-II and ASAP-III trials and international abatacept trial (IM101603) from whom a labial (n=13) or parotid (n=28) salivary gland biopsy was obtained at baseline and after 24 weeks of treatment with abatacept were included. Biopsies were analysed for SjD related histopathological features before and after abatacept (n=25) or placebo (n=16) treatment.

Field testing and clinical validation of the mSQUASH to measure physical activity in patients with Sjögren's disease.

Objectives: Regular physical activity is recommended in patients with rheumatic diseases. In order to uniformly measure physical activity, our aim was to perform field testing of the modified Short QUestionnaire to ASsess Health enhancing physical activity (mSQUASH) in Sjögren's disease (SjD), together with other rheumatic diseases, and to investigate construct validity and test-retest reliability of the mSQUASH in patients with SjD.

Methods: The mSQUASH was tested by conducting semi-structured interviews in patients with SjD (n=10), systemic lupus erythematosus (n=10), giant cell arteritis/polymyalgia rheumatica (n=10) and axial spondyloarthritis (n=13) to check for understandability, interpretation and relevance.

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

Objectives: 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).

Methods: 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.

Serum and Tissue Biomarkers Associated With Composite of Relevant Endpoints for Sjögren Syndrome (CRESS) and Sjögren Tool for Assessing Response (STAR) to B Cell-Targeted Therapy in the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS).

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints.

Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre- and post-treatment from the Trial of Anti-B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing.

Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class-switched memory B cells within the SG.

Why do drug treatments fail in Sjögren's disease? Considerations for treatment, trial design and interpretation of clinical efficacy.

Introduction: Despite ongoing efforts to develop effective therapeutics, no disease-modifying drugs have been officially licensed for the indication of Sjögren's disease (SjD). This is partly due to heterogeneity in disease manifestations, which complicates drug target selection, trial design and interpretation of clinical efficacy in SjD.

Areas Covered: Here, we summarize developments and comment on challenges in 1) identifying the right target for treatment, 2) selection of the primary study endpoint for trials and definition of clinically relevant response to treatment, 3) inclusion criteria and patient stratification, 4) distinguishing between disease activity and damage and 5) establishing the effect of treatment considering measurement error, natural variation, and placebo or nocebo responses.

Association of Circulating Antibody-Secreting Cell Maturity With Disease Features in Primary Sjögren's Syndrome.

Objective: B cell hyperactivity plays an important role in primary Sjögren's syndrome (SS). We undertook this study to better understand the B cell effector branch, namely antibody-secreting cells (ASCs) in primary SS, and to examine the quantity, maturity, and inflammatory properties of ASCs in primary SS patients.

Methods: Circulating ASCs, defined as CD3-CD14-CD27+CD38++ cells, from 21 primary SS patients and 10 healthy controls were assessed using spectral flow cytometry.

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

Objectives: 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.

Methods: 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.

Safety and efficacy of SARS-CoV-2 vaccination in 1237 patients with primary Sjögren syndrome.

Objectives: To investigate the safety and efficacy of SARS-Cov-2 vaccination in patients with primary Sjögren syndrome (pSS) due to scarcity of data in this population.

Methods: By the first week of May 2021, all Big Data SS Consortium centres patients who had received at least one dose of any SARS-CoV-2 vaccine were included in the study. The in-charge physician asked patients about local and systemic reactogenicity to collect SARS-CoV-2 vaccination data.

Selection of study endpoints and patients for clinical trials in primary Sjögren's syndrome.

In the last decade, many randomised controlled trials (RCTs) with biological DMARDs (bDMARDs) have been performed in patients with primary Sjögren's syndrome (pSS). Unfortunately, no bDMARD has yet been approved for systemic treatment of pSS. The heterogeneity of disease manifestations raises two essential questions: 1) which outcome measure is valid, reliable and responsive to demonstrate treatment efficacy and should be used as primary study endpoint? and 2) which pSS patients should be included in clinical trials? Both the selection of the primary study endpoint and the selection of patients are crucial and evolving issues in clinical trial design in pSS.

Immunisation with Coronavirus-2 vaccines induces potent antibody responses and does not aggravate the lymphocyte compartment of primary Sjögren's syndrome patients.

Objectives: The peripheral lymphocyte compartment of patients with primary Sjögren's syndrome (pSS) differs strongly from healthy individuals. Whether this altered lymphocyte composition also changes abnormally during immune reactions, especially by novel CoV-2-vaccines, is unknown.

Methods: Peripheral blood mononuclear cells (PBMC) from 26 pSS patients and 6 healthy controls were compared before Coronavirus-2 (CoV-2) vaccination (Pfizer/BNT162b2, Moderna/mRNA-1273, AstraZeneca/AZD122 ChAdOx1 nCoV-19) and 7 days after secondary vaccination.

Long-term abatacept treatment for 48 weeks in patients with primary Sjögren's syndrome: The open-label extension phase of the ASAP-III trial.

Objective: To investigate treatment efficacy of long-term abatacept treatment in pSS patients.

Methods: The single-centre ASAP-III trial consisted of two phases: the randomised, double-blind, placebo-controlled phase (1:1 randomisation) from baseline to week 24, of which results have been published previously, and the open-label extension phase from week 24 to 48, in which all patients received abatacept. Main inclusion criteria were fulfilment of the AECG criteria, positive gland biopsy, disease duration ≤ 7 years and ESSDAI ≥ 5.

Differences in presentation between paediatric- and adult-onset primary Sjögren's syndrome patients.

Objectives: Primary Sjögren's syndrome (pSS) is a rare disease in paediatric patients. Presenting symptoms differ from those in adult patients. The aim of this study was to evaluate presenting symptoms, classification criteria and clinical assessments, including salivary gland ultrasonography (SGUS), at disease onset in paediatric and adult patients with pSS.

Development and performance of the Clinical Trials ESSDAI (ClinTrialsESSDAI), consisting of frequently active clinical domains, in two randomised controlled trials in primary Sjögren's syndrome.

Objectives: To develop and evaluate the Clinical Trials EULAR Sjögren's Syndrome Disease Activity Index (ClinTrialsESSDAI), consisting of frequently active clinical domains of the ESSDAI, using two randomised controlled trials in primary Sjögren's syndrome (pSS).

Methods: The ASAP-III trial in abatacept (80 pSS patients) and TRACTISS trial in rituximab (133 pSS patients) were analysed. The most frequently active clinical domains were selected, and ClinTrialsESSDAI total score was calculated using existing weightings of the ClinESSDAI (which also excludes the biological domain).

Clinical determinants of vaginal dryness in patients with primary Sjögren's syndrome.

Objectives: The majority of women with primary Sjögren's syndrome (pSS) suffer from vaginal dryness, which negatively impacts daily and sexual activities. As little is known about the aetiology and clinical context of this complaint, this study investigated the relationship between vaginal dryness and other clinical parameters associated with pSS.

Methods: Female participants of the REgistry of Sjögren syndrome at UMCG - LongiTudinal (RESULT) cohort who fulfilled ACR-EULAR and/or AECG classification criteria for pSS were included, using baseline data for analyses.

Change in disease activity is associated with TNF-α inhibitor serum levels in patients with axial spondyloarthritis in daily clinical practice.

Objectives: To investigate, in daily clinical practice, TNF-α inhibitor serum trough levels in patients experiencing an increase in axial spondyloarthritis (ax-SpA) related symptoms. Secondly, to explore if these serum trough levels are associated with disease activity (DA) and/or change in DA.

Methods: Patients from the GLAS cohort treated with TNF-α inhibitors who had a serum trough level measurement during follow-up because of an increase in ax-SpA related symptoms between June 2015 and June 2018 were included.

Ten years of the ESSDAI: is it fit for purpose?

Primary Sjögren's syndrome (pSS) is a very heterogeneous disease with systemic manifestations such as arthritis, skin, lung and renal involvement. To be able to assess systemic disease activity, the EULAR Sjögren's syndrome disease activity index (ESSDAI) was developed for use in daily clinical practice and in clinical trials. Since its development it has been widely used in cohort studies and clinical trials.