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Primary Sjögren’s syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60 years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65 years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the recently published 2020 European League Against Rheumatism (EULAR) recommendations for the management of the disease with topical and systemic therapies. These recommendations are applicable to all patients with primary SjS regardless of age at diagnosis, although the therapeutic management in older patients requires additional considerations. Older patients are more likely to have pulmonary, liver, kidney, or heart-related comorbidities (even cognitive disturbances); caution is required when most drugs are used, including muscarinic agents, systemic corticosteroids and synthetic immunosuppressants. It is also important to monitor the use of eye drops containing steroids due to the increased risk of developing cataracts, a frequent ocular complication in the older population. In contrast, the majority of drugs that can be used topically (pilocarpine rinses, eye drops containing topical non-steroidal anti-inflammatory drugs (NSAIDs) or cyclosporine A, topical dermal formulations of NSAIDs) have shown an acceptable safety profile in older patients, as well as rituximab. A rigorous evaluation of the medical history of older patients is essential when drugs included in the EULAR guidelines are prescribed, with special attention to factors frequently related to ageing, such as polypharmacy, the existence of organ-specific comorbidities, or the enhanced susceptibility to infections. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments. © 2018

Labial salivary gland (LSG) biopsy is used in the classification of primary Sjögren's syndrome (PSS) and in patient stratification in clinical trials. It may also function as a biomarker. The acquisition of tissue and histological interpretation is variable and needs to be standardised for use in clinical trials. A modified European League Against Rheumatism consensus guideline development strategy was used. The steering committee of the ad hoc working group identified key outstanding points of variability in LSG acquisition and analysis. A 2-day workshop was held to develop consensus where possible and identify points where further discussion/data was needed. These points were reviewed by a subgroup of experts on PSS histopathology and then circulated via an online survey to 50 stakeholder experts consisting of rheumatologists, histopathologists and oral medicine specialists, to assess level of agreement (0-10 scale) and comments. Criteria for agreement were a mean score ≥6/10 and 75% of respondents scoring ≥6/10. Thirty-nine (78%) experts responded and 16 points met criteria for agreement. These points are focused on tissue requirements, identification of the characteristic focal lymphocytic sialadenitis, calculation of the focus score, identification of germinal centres, assessment of the area of leucocyte infiltration, reporting standards and use of prestudy samples for clinical trials. We provide standardised consensus guidance for the use of labial salivary gland histopathology in the classification of PSS and in clinical trials and identify areas where further research is required to achieve evidence-based consensus. © 2016 BMJ Publishing Group Limited.

Objectives This phase 2 proof-of-concept study (NCT02610543) assessed efficacy, safety and effects on salivary gland inflammation of seletalisib, a potent and selective PI3Kδ inhibitor, in patients with moderate-to-severe primary Sjögren’s syndrome (PSS). Methods Adults with PSS were randomized 1:1 to seletalisib 45 mg/day or placebo, in addition to current PSS therapy. Primary end points were safety and tolerability and change from baseline in EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score at week 12. Secondary end points included change from baseline at week 12 in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score and histological features in salivary gland biopsies. Results Twenty-seven patients were randomized (seletalisib n = 13, placebo n = 14); 20 completed the study. Enrolment challenges led to early study termination with loss of statistical power (36% vs 80% planned). Nonetheless, a trend for improvement in ESSDAI and ESSPRI [difference vs placebo: –2.59 (95% CI: –7.30, 2.11; P=0.266) and –1.55 (95% CI: –3.39, 0.28), respectively] was observed at week 12. No significant changes were seen in saliva and tear flow. Serious adverse events (AEs) were reported in 3/13 of patients receiving seletalisib vs 1/14 for placebo and 5/13 vs 1/14 discontinued due to AEs, respectively. Serum IgM and IgG concentrations decreased in the seletalisib group vs placebo. Seletalisib demonstrated efficacy in reducing size and organisation of salivary gland inflammatory foci and in target engagement, thus reducing PI3K-mTOR signalling compared with placebo. Conclusion Despite enrolment challenges, seletalisib demonstrated a trend towards clinical improvement in patients with PSS. Histological analyses demonstrated encouraging effects of seletalisib on salivary gland inflammation and organisation. Trial registration https://clinicaltrials.gov, NCT02610543.

Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.