-
Nature Medicine Jun 2024Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein,... (Randomized Controlled Trial)
Randomized Controlled Trial
Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 .
Topics: Humans; Sjogren's Syndrome; CD40 Ligand; Double-Blind Method; Female; Middle Aged; Male; Adult; Aged; Treatment Outcome
PubMed: 38839899
DOI: 10.1038/s41591-024-03009-3 -
Rheumatology International Jul 2024Primary Sjögren's Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects...
BACKGROUND
Primary Sjögren's Syndrome (pSS) is a systemic chronic autoimmune disorder that contributes to dry mouth (xerostomia) and eyes (xerophthalmia). It mainly affects females between 40 and 60 years old. So far, there is no treatment to cure SS; however, there is a list of medications that can ameliorate the symptoms. In addition, there has been no single test until now to detect pSS, but clinical and immunological investigations are applied as diagnostic tools. Therefore, this study aimed to explore the characteristics of pSS in Saudi patients based on the onset of the disease through laboratory findings and pharmaceutical management.
METHODOLOGY
This retrospective study examined diagnosed patients with pSS between 2018 and 2023 from the National Guard Hospital, Saudi Arabia. Data of pSS patients was categorized into two groups: early (under 40 years old) and late-onset (40 years old and above). Data on demographic information, mortality rate, and blood tests such as complete blood count (CBC), creatinine, erythrocyte sedimentation rate (ESR), and vitamin levels, in addition to prescribed medications, were collected from the patient's medical record. Chi-square and t-tests were mainly used, and statistical significance was determined at a P-value less than 0.05.
RESULTS
A total of 453 patients were included in the study, where the early-onset group comprised 136 and the late-onset group comprised 317 patients. The mean age of the early and late onset was 34.2 and 60.4, respectively. ESR was significantly higher in the early (46.3 mm/hr) and late-onset (49.8 mm/hr). The most common medication used by all pSS patients was hydroxychloroquine. However, artificial tears were mainly observed in the late-onset group. Other medications, such as pilocarpine, methotrexate, and azathioprine, were prescribed to pSS patients to a lesser extent.
CONCLUSION
This study suggests that the onset of pSS could occur even before the age of 40 among Saudi citizens. Notably, elevated ESR levels appeared to be a feature of pSS, which was consistent with other previous findings. The variability of some medications between early-onset and late-onset pSS may indicate disease progression. However, further investigations are required to confirm this observation.
Topics: Humans; Sjogren's Syndrome; Female; Adult; Retrospective Studies; Middle Aged; Male; Age of Onset; Saudi Arabia; Blood Sedimentation; Aged; Antirheumatic Agents
PubMed: 38839658
DOI: 10.1007/s00296-024-05626-0 -
Clinical Case Reports Jun 2024In a patient with anti-aminoacyl tRNA synthetase antibody and anti-OJ antibody syndrome, interventions likes warming, prostaglandins, and antiplatelets failed. However,...
KEY CLINICAL MESSAGE
In a patient with anti-aminoacyl tRNA synthetase antibody and anti-OJ antibody syndrome, interventions likes warming, prostaglandins, and antiplatelets failed. However, prednisolone pulse treatment rapidly halted disease progression. Patients with mild interstitial pneumonia, myositis, and extremity necrosis should be promptly considered for anti-synthetase syndrome and receive immunosuppression after ruling out other causes.
ABSTRACT
Anti-aminoacyl tRNA synthetase (ARS) autoantibodies are myositis-specific, and patients who test positive for ARS and have common clinical features are usually diagnosed with antisynthetase antibody syndrome (antisynthetase syndrome). Anti-ARS antibodies include histidyl-tRNA synthetase-1 (Jo-1), anti-threonyl (PL-7), anti-alanyl (PL-12), anti-glycyl (EJ), anti-asparaginyl (KS), anti-tyrosyl (Ha), and anti-phenylalanyl (Zo) tRNA synthetases. Among these, anti-isoleucyl tRNA synthetase (OJ) autoantibodies are extremely rare, and patients with these are frequently complicated by interstitial pneumonia. We report the case of an older man with ARS antibody syndrome who tested positive for anti-OJ and anti-Sjögren's-syndrome-related antigen A (Ro-52) antibodies. He had muscle weakness due to myositis and unparalleled rapid and severe finger necrosis. Pulsed prednisolone effectively treated the myositis symptoms and terminated the progression of finger necrosis.
PubMed: 38831985
DOI: 10.1002/ccr3.8990 -
Frontiers in Pharmacology 2024Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest... (Review)
Review
Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.
PubMed: 38828450
DOI: 10.3389/fphar.2024.1377055 -
Cureus May 2024Autoimmune thyroid disease (AITD) encompasses a spectrum of conditions ranging from Graves' disease (GD) to Hashimoto's thyroiditis (HT). These conditions often coexist...
Autoimmune thyroid disease (AITD) encompasses a spectrum of conditions ranging from Graves' disease (GD) to Hashimoto's thyroiditis (HT). These conditions often coexist with other autoimmune diseases (AIDs). This case describes a young woman in her 20s who transitioned from GD to HT during her first pregnancy, while having another coexisting AID, Sjogren's syndrome (SS). AITD and SS are recognized as the most common polyautoimmune diseases, sharing many common pathophysiological characteristics such as the presence of lymphocytic infiltrates, similar expressions of the human leukocyte antigen molecules, and predisposing environmental factors. This case underscores the importance for physicians to be vigilant regarding the possibility of changing antibodies in AITD and the potential for concurrent AIDs in a single individual. It highlights the need for screening such patients for comprehensive management.
PubMed: 38826946
DOI: 10.7759/cureus.59446 -
Scientific Reports May 2024The role of spirituality in health and disease is a complex and emerging area of research. Incorporating spirituality into the bio-psycho-social model of health and...
The role of spirituality in health and disease is a complex and emerging area of research. Incorporating spirituality into the bio-psycho-social model of health and disease leading to the bio-psycho-social-spiritual model provides a more comprehensive framework. In this context, chronic disorders like primary Sjögren's syndrome (pSS) are of interest due to their intricate interactions between biological, psychological, and spiritual factors. This study explored the relationship between spirituality, immune parameters, and disease activity in pSS patients. Data from 108 patients were analyzed, including self-assessed spirituality (answering to direct questions and completing the Spiritual Transcendence Scale), immunological parameters and disease activity scores. The findings revealed several associations. Individuals with spiritual attitudes or engaged in regular prayer/meditation showed lower serum levels of autoantibodies specific to pSS and lower disease activity scores. Spiritual engagement was also linked to decreased perceived skin and tracheal dryness, suggesting potential benefits for physical symptoms. These findings suggest that spirituality may play a significant role in modulating immune responses and disease activity in pSS patients. The study underscores the importance of considering spirituality as an integral part of the holistic approach to health and disease, further expanding the understanding of the interconnectedness of biological, psychological, and spiritual dimensions.
Topics: Humans; Sjogren's Syndrome; Female; Spirituality; Middle Aged; Cross-Sectional Studies; Male; Adult; Aged; Autoantibodies
PubMed: 38816520
DOI: 10.1038/s41598-024-62801-w -
RMD Open May 2024This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases.
OBJECTIVES
This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases.
METHODS
A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022.
RESULTS
This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival.
CONCLUSIONS
Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.
Topics: Humans; Female; Pregnancy; Sjogren's Syndrome; Adult; Pregnancy Outcome; Retrospective Studies; Pregnancy Complications; Risk Factors; China; Abortion, Spontaneous; Case-Control Studies; Heparin, Low-Molecular-Weight
PubMed: 38806189
DOI: 10.1136/rmdopen-2023-003616 -
Seminars in Arthritis and Rheumatism Aug 2024To assess whether addition of the salivary gland ultrasonography (SGUS) OMERACT score influences the performance of the 2016 ACR/EULAR classification criteria for...
OBJECTIVES
To assess whether addition of the salivary gland ultrasonography (SGUS) OMERACT score influences the performance of the 2016 ACR/EULAR classification criteria for Sjögren's disease (SjD) in daily clinical practice.
METHODS
Patients visiting the Sjögren Expertise centre in the University Medical Center Groningen for a diagnostic trajectory because of a suspicion of SjD were included. SGUS was performed of both parotid and submandibular glands. ROC analysis was used to assess the accuracy to predict clinical diagnosis of SjD with the SGUS OMERACT score, and by adding the SGUS OMERACT score to the ACR/EULAR criteria. Furthermore, the performance of the SGUS OMERACT and total SGUS Hocevar score were compared.
RESULTS
In total, 419 consecutive patients were included. ROC analysis of the highest SGUS OMERACT score out of all four salivary glands (range 0-3) showed good accuracy (AUC 0.849) to predict clinical diagnosis of SjD, comparable to the accuracy of the total SGUS OMERACT score (range 0-12; AUC 0.868) and total Hocevar score (range 0-48; AUC 0.864). When incorporating the highest SGUS OMERACT score (cut-off score of ≥2) as additional item in the ACR/EULAR criteria, accuracy remained excellent (AUC 0.974), and clinical diagnosis could be predicted with a sensitivity of 96.4% and specificity of 86.5%.
CONCLUSION
The accuracy of the ACR/EULAR classification criteria for predicting the clinical diagnosis of SjD remained excellent after incorporating the SGUS OMERACT score and extends the diagnostic options in patients suspected with SjD.
Topics: Humans; Ultrasonography; Female; Middle Aged; Male; Salivary Glands; Sjogren's Syndrome; Aged; Adult; Severity of Illness Index
PubMed: 38805898
DOI: 10.1016/j.semarthrit.2024.152473 -
Heliyon May 2024N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS)...
OBJECTIVES
N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic.
METHODS
We screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients.
RESULTS
The XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation.
CONCLUSIONS
m7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.
PubMed: 38803884
DOI: 10.1016/j.heliyon.2024.e31307 -
Seminars in Arthritis and Rheumatism Aug 2024Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases...
INTRODUCTION
Classification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases (CTDs) represent a real-world cohort.
METHODS
A comprehensive review of all major published phase-III trials in CTDs was performed (clinicaltrials.gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort.
RESULTS
There were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials (N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our real-world CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjögren's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria.
CONCLUSION
In an unselected, real-world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.
Topics: Humans; Connective Tissue Diseases; Patient Selection; Female; Eligibility Determination; Male; Clinical Trials, Phase III as Topic; Cohort Studies; Middle Aged; Adult
PubMed: 38796923
DOI: 10.1016/j.semarthrit.2024.152463