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Frontiers in Pharmacology 2023To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Databases such as Pubmed, Embase, Sinomed were searched (as...
To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], = 0.003), ACR50 (RR 1.80 [1.43, 2.26], < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], < 0.00001), RF (SMD -1.65 [-2.48, -0.82], < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. : (CRD42021289489).
PubMed: 38143490
DOI: 10.3389/fphar.2023.1189142 -
Rheumatology (Oxford, England) Mar 2016There is conflicting evidence regarding prognosis in patients with primary SS (pSS). The aim of this study was to estimate the rate, risk factors and causes of mortality... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
There is conflicting evidence regarding prognosis in patients with primary SS (pSS). The aim of this study was to estimate the rate, risk factors and causes of mortality in patients with pSS through a systematic review and meta-analysis.
METHODS
Through a systematic review of multiple databases through October 2014, we identified cohort studies reporting relative risk (compared with standardized population), risk factors and causes of mortality in patients with pSS. We estimated summary risk ratios (RRs) with 95% CIs using random effects model.
RESULTS
We identified 10 studies with 7888 patients (91% females) with pSS, of whom 682 patients died over a median average follow-up of 9 years. The pooled standardized mortality ratio in patients with pSS was 1.38 (95% CI 0.94, 2.01). Leading causes of mortality were cardiovascular diseases, solid-organ and lymphoid malignancies and infections; however, it is unclear whether these observed causes were overrepresented in patients with pSS as compared with the general population. Risk factors associated with increased mortality were advanced age at diagnosis [RR 1.09 (95% CI 1.07, 1.12)], male sex [RR 2.18 (95% CI 1.45, 3.27)], parotid enlargement [RR 1.81 (95% CI 1.02, 3.21)], abnormal parotid scintigraphy [RR 2.96 (95% CI 1.36, 6.45)], extraglandular involvement [RR 1.77 (95% CI 1.06, 2.95)], vasculitis [RR 7.27 (95% CI 2.70, 19.57)], anti-SSB positivity [RR 1.45 (95% CI 1.03, 2.04)], low C3 [RR 2.14 (95% CI 1.38, 3.32)] and C4 [RR 3.08 (95% CI 2.14, 4.42)] and cryoglobulinaemia [RR 2.62 (95% CI 1.77, 3.90)].
CONCLUSION
pSS is not associated with an increase in all-cause mortality as compared with the general population. However, a subset of patients with extraglandular involvement, vasculitis, hypocomplementaemia and cryoglobulinaemia may be at increased risk of mortality and require close follow-up.
Topics: Adult; Age Factors; Aged; Cause of Death; Cohort Studies; Disease Progression; Disease-Free Survival; Female; Humans; Male; Middle Aged; Risk Assessment; Severity of Illness Index; Sex Factors; Sjogren's Syndrome; Survival Rate
PubMed: 26412810
DOI: 10.1093/rheumatology/kev354 -
Evidence-based Complementary and... 2017To evaluate the clinical efficacy and safety of total glucosides of paeony (TGP) for primary Sjögren's syndrome (pSS). (Review)
Review
OBJECTIVE
To evaluate the clinical efficacy and safety of total glucosides of paeony (TGP) for primary Sjögren's syndrome (pSS).
METHODS
Eight electronic databases were searched from their inception to July 2016. Clinical randomized controlled trials (RCTs) were included. The study quality was evaluated according to the standard suggested in the Cochrane Handbook. RevMan 5.1 was used for statistical analysis.
RESULTS
Seven RCTs involving 443 patients were included. The results showed that TGP combined with an immunosuppressant (IS) showed greater efficacy for improving the saliva flow test of pSS compared to immunosuppressant alone (WMD -6.88, 95% CI -9.02 to -4.74, and < 0.00001). And the same trend favouring TGP-IS dual combination was found in Schirmer test (WMD 1.63, 95% CI 0.26 to 3.01, and = 0.02), ESR (WMD 7.33, 95% CI -10.08 to -4.59, and < 0.00001), CRP (WMD -6.00, 95% CI -7.17 to -4.83, and < 0.00001), IgM (WMD = -0.42, 95% CI -0.70 to 0.13, and = 0.004), and IgG (WMD -3.22, 95% CI -4.32 to -2.12, and < 0.00001) analysis. However, TGP did not affect IgA (WMD 0.53, 95% CI -1.34 to -0.29, and = 0.20). The adverse events manifested no significant differences between the two groups.
CONCLUSIONS
The TGP-IS combination is superior to IS alone in the treatment of pSS. However, due to the low quality of included studies, high-quality RCTs are needed to confirm the beneficial effects of TGP.
PubMed: 28642798
DOI: 10.1155/2017/3242301 -
Rheumatology (Oxford, England) Sep 2021It remains debated whether patients with primary Sjögren's syndrome (pSS) are at greater risk of mortality. We aimed to determine the magnitude of all-cause mortality... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
It remains debated whether patients with primary Sjögren's syndrome (pSS) are at greater risk of mortality. We aimed to determine the magnitude of all-cause mortality risk in patients with pSS compared with the general population through a systematic review and meta-analysis.
METHODS
We searched PubMed, EMBASE and Cochrane Library for studies published from inception to October 2020. Stata meta-analysis software was used to calculate the pooled risk estimates for mortality (standardized mortality ratio, SMR).
RESULTS
Our search identified 2796 articles, of which 14 studies with 14 584 patients were eventually included for the analysis. A total of 902 deaths were observed. Overall, we found a 1.46-fold increased risk of death in pSS patients when compared with the general population [meta-standardized mortality ratio (SMR): 1.46, 95% CI: 1.10, 1.93]. Subgroup analyses showed that mortality risks were higher in European countries (meta-SMR: 1.55, 95% CI: 1.04, 2.33), in retrospective studies (meta-SMR: 1.50, 95% CI: 1.09, 2.05), in studies based on referral cohorts (meta-SMR: 1.55, 95% CI: 1.04, 2.30), in studies that enrolled >500 patients (meta-SMR: 1.70, 95% CI: 1.11, 2.61) and in studies with follow-up time longer than 8 years (meta-SMR: 1.55, 95% CI: 0.87, 2.77). Significantly greater mortality risk was found in patients with older age, male gender, vasculitis, interstitial lung disease, low complements, positive anti-La/SSB and cryoglobulinaemia.
CONCLUSION
The existing data indicated ∼50% increase of mortality among patients with pSS compared with the general population. More attention should be paid to those patients with poor prognostic factors.
Topics: Cause of Death; Humans; Risk Factors; Sjogren's Syndrome
PubMed: 33878179
DOI: 10.1093/rheumatology/keab364 -
Antioxidants (Basel, Switzerland) Aug 2022Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation... (Review)
Review
Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the locus with various autoimmune diseases and to provide a systemic review on potential mechanisms underlying the effect of the causal risk variants. The frequencies of the two most extensively investigated polymorphisms within the locus, rs117026326 and rs201802880, vary remarkably across the world, with the highest frequencies in East Asian populations. Meta-analysis showed that the locus is significantly associated with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, and neuromyelitis optica spectrum disorder. The causal rs201802880 polymorphism leads to an amino acid substitution of p.Arg90His in the p47phox subunit of the phagocyte NADPH oxidase. The autoimmune disease risk His90 variant results in a reduced ROS production in phagocytes. Clinical and experimental evidence shows that the hypoactive His90 variant might contribute to the development of autoimmune disorders via multiple mechanisms, including impairing the clearance of apoptotic cells, regulating the mitochondria ROS-associated formation of neutrophil extracellular traps, promoting the activation and differentiation of autoreactive T cells, and enhancing type I IFN responses. In conclusion, the identification of the association of with autoimmune disorders demonstrates that ROS is an essential regulator of immune tolerance and autoimmunity mediated disease manifestations.
PubMed: 36009308
DOI: 10.3390/antiox11081589 -
Rheumatology International Jan 2015To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive... (Meta-Analysis)
Meta-Analysis Review
To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.
Topics: Female; Humans; Lymphoma; Male; Prognosis; Risk Factors; Sjogren's Syndrome
PubMed: 24899571
DOI: 10.1007/s00296-014-3051-x -
Therapeutics and Clinical Risk... 2018Although it is well established that systemic lupus erythematosus (SLE) negatively affects pregnancy outcomes, there is insufficient evidence on the effect of lupus... (Review)
Review
BACKGROUND
Although it is well established that systemic lupus erythematosus (SLE) negatively affects pregnancy outcomes, there is insufficient evidence on the effect of lupus nephritis (LN) on antenatal management and pregnancy outcomes. We performed a systematic review and meta-analysis to determine the association of LN with management and pregnancy outcomes in SLE patients.
METHODS
Embase, Medline, Cochrane, and ClinicalTrials.gov were carefully searched for relevant English and Chinese language studies. A total of 2,987 articles were reviewed. Data were extracted that compared management and pregnancy outcomes in SLE pregnant women with LN vs without LN. Risk of bias was assessed by a modified version of the Newcastle-Ottawa Scale and the STROBE checklist. Combined odds ratios (OR) and 95% confidence intervals (CI) were obtained and sensitivity analysis was performed using RevMan 5.3 software.
RESULTS
Sixteen studies, including 1,760 pregnant patients with SLE, were included. Gestational hypertension (OR=5.65, 95% CI=2.94-10.84), preeclampsia (OR=2.84, 95% CI=1.87-4.30), SLE flare (OR=2.66, 95% CI=1.51-4.70), renal flare (OR=15.18, 95% CI=5.89-39.14), proteinuria (OR=8.86, 95% CI=4.75-16.52), and hypocomplementemia (OR=2.86, 95% CI=1.68-4.87) were significantly affected in pregnant women with LN. Anti-Sjögren's syndrome-related antigen A/Ro autoantibodies were negatively associated with pregnant women with LN (OR=0.57, 95% CI=0.33-0.98). Pregnant women with LN presented a significant decrease in live births (OR=0.62, 95% CI=0.49-0.80) and a significant increase in preterm births (OR=1.92, 95% CI=1.49-2.49) and fetal growth restriction (OR=1.43, 95% CI=1.08-1.91). Regarding antenatal management, steroids (OR=2.48, 95% CI=1.59-3.87) and immunosuppressant treatment (OR=6.77, 95% CI=3.30-13.89) were more frequently used in women with LN.
CONCLUSION
This review identified a significant association between the aforementioned outcomes and SLE pregnant patients with LN. In patients with SLE, LN increased the risks for adverse pregnancy outcomes and the use of medication. Therefore, special treatment and close monitoring should be allocated to pregnant women with LN.
PubMed: 29785115
DOI: 10.2147/TCRM.S160760 -
Clinical and Experimental Rheumatology 2020To identify the role of nailfold capillaroscopy (NC) in Sjögren's syndrome (SS).
OBJECTIVES
To identify the role of nailfold capillaroscopy (NC) in Sjögren's syndrome (SS).
METHODS
The literature was systematically reviewed in three databases. All published original studies which assess patients with SS by NC were revised. A quality assessment was applied to all studies based on population description, presence of a control group, presence of instrumental specifications and/or standardly applied NC methodology, presence of clear descriptions of capillaroscopic characteristics and based on the used statistical analysis. The capillaroscopic findings per study were described in a EULAR consented standardised way. Significant associations of capillaroscopic characteristics in SS patients with clinical and laboratory variables were summarised.
RESULTS
The search resulted in 869 hits. Based on title and abstract screening 29 original studies were identified and of these, 14 full texts described an assessment by NC in SS. Seven studies were retained after performing a critical quality assessment. One study compared NC in SS with healthy controls and attested a lower capillary density in SS. Concerning clinical associations, capillary density was associated with Raynaud's phenomenon in two studies and with interstitial lung disease or systemic manifestations in one study each. No association between serologic features (anti-nuclear antibodies, anti-SSA, anti-SSB and anti-RF) and NC characteristics were found.
CONCLUSIONS
A small number of studies have investigated the role of NC in SS. More studies, including prospective follow up studies with standard NC evaluation in SS are needed.
Topics: Humans; Microscopic Angioscopy; Nails; Prospective Studies; Raynaud Disease; Sjogren's Syndrome
PubMed: 33025880
DOI: No ID Found -
Journal of Clinical Medicine Mar 2024Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder characterized by organ-specific symptoms in the salivary and lacrimal glands, as well as systemic... (Review)
Review
Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder characterized by organ-specific symptoms in the salivary and lacrimal glands, as well as systemic manifestations. Fatigue, a prominent aspect, significantly influences the overall quality of life for individuals with pSS. This review seeks to evaluate the impact of fatigue by exploring its consequences, potential causes, and effects on physical and psychological well-being, while also investigating its management strategies. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Initially identifying 78 articles in reputable international medical databases, we applied eligibility criteria and removed duplicates, resulting in 19 articles for qualitative synthesis. This review delves into the predictive factors for heightened fatigue in pSS, encompassing rheumatoid factor levels, erythrocyte sedimentation rate, and immunoglobulin G levels. Sleep disturbances, specifically nighttime pain and nocturia, emerged as determinants of persistent daytime fatigue. Cognitive impairment in pSS involves deteriorations in global memory, executive functioning, and attentional resources. Furthermore, functional limitations in pSS impact patients' quality of life. The significance of fatigue in pSS, its consequences, and profound influence on the quality of life necessitate further research for a more comprehensive understanding of this complex issue.
PubMed: 38541763
DOI: 10.3390/jcm13061537 -
Allergy Sep 2021Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of...
BACKGROUND
Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune-mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell-activating factor (BAFF).
OBJECTIVE
To evaluate belimumab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics.
METHODS
The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist guided the reporting of the data. We searched the PubMed database between October 4, 2016, and June 23, 2019, concentrating on immune-mediated disorders.
RESULTS
The literature search identified 583 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 17 articles were finally included in a narrative synthesis.
CONCLUSIONS
Belimumab is both safe and effective for the treatment of systemic lupus erythematosus. Results were further promising for the use of belimumab in patients with rheumatoid arthritis and Sjögren's syndrome. Conversely, results using belimumab in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and myasthenia gravis were rather disappointing.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Humans; Immune System Diseases; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Treatment Outcome
PubMed: 33368349
DOI: 10.1111/all.14704