Low-dose glucocorticoid should be withdrawn or continued in systemic lupus erythematosus? A systematic review and meta-analysis on risk of flare and damage accrual

Rheumatology ◽  
2021 ◽  
Author(s):  
Lanlan Ji ◽  
Wenhui Xie ◽  
Zhuoli Zhang

Abstract Objective To assess the risk of flare and damage accrual after low dose glucocorticoids (GC) discontinuation in systemic lupus erythematosus (SLE). Methods We performed a comprehensive literature search of PubMed, EMBASE, Cochrane library and Scopus databases from inception to July 2020 for studies concerning relapses/damage accrual in SLE patients. Pooled incidence rates of flare and time to flare with their 95% confidence intervals (CI) after GC withdrawal were calculated. Summary risk ratio (RR) and 95% CI of flare/organ damage accrual risk were computed using a random or fixed effects model. Results 738 SLE patients with GC discontinuation in 17 publications were eligible for the final analysis. In the primary meta-analysis, the pooled incidence of flare was 24% (95% CI 21-27%) and 13% (95% CI 8-18%) for global and major flare respectively. Pooled time to flare was 21.08 (95% CI 9.32-32.85) months. In the secondary meta-analysis, GC discontinuation showed an increased risk of flare comparing with GC continuation [RR (95% CI) =1.38 (1.01-1.89)], but the risk of major flares was not increased (RR = 1.77, 95% CI 0.40-7.83). Moreover, GC withdrawal was associated with a borderline reduction of risk in SDI increase in comparison with GC continuation (RR = 0.64, 95% CI 0.38 - 1.09). Conclusion GC discontinuation leads to a slightly increased risk of flare, however no increase in major flare and a borderline reduction of risk in further damage in SLE patients. Baseline screening for candidate patients and long-term follow up after GC withdrawal are needed to reliably evaluate the organ damage increase.

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e031850 ◽  
Author(s):  
Irene B Murimi-Worstell ◽  
Dora H Lin ◽  
Henk Nab ◽  
Hong J Kan ◽  
Oluwadamilola Onasanya ◽  
...  

ObjectiveAt least half of patients with systemic lupus erythematosus (SLE) develop organ damage as a consequence of autoimmune disease or long-term therapeutic steroid use. This study synthesised evidence on the association between organ damage and mortality in patients with SLE.DesignSystematic review and meta-analysis.MethodsElectronic searches were performed in PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Sciences Literature for observational (cohort, case-control and cross-sectional) studies published between January 2000 and February 2017. Included studies reported HRs or ORs on the association between organ damage (measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score) and mortality. Study quality was assessed using the modified Newcastle-Ottawa assessment. Pooled HRs were obtained using the DerSimonian and Laird random-effects model. Heterogeneity was assessed using the Cochrane Q (Q) and I2 statistics.ResultsThe search yielded 10 420 articles, from which 21 longitudinal studies were selected. Most studies (85%) were of high quality. For 10 studies evaluating organ damage (SDI) as a continuous variable and reporting HR as a measure of association, a 1-unit increase in SDI was associated with increased mortality; pooled HR was 1.34 (95% CI: 1.24 to 1.44, p<0.001; Q p=0.027, I2=52.1%). Exclusion of one potential outlying study reduced heterogeneity with minimal impact on pooled HR (1.33 (95% CI: 1.25 to 1.42), p<0.001, Q p=0.087, I2=42.0%). The 11 remaining studies, although they could not be aggregated because of their varying patient populations and analyses, consistently demonstrated that greater SDI was associated with increased mortality.ConclusionsOrgan damage in SLE is consistently associated with increased mortality across studies from various countries. Modifying the disease course with effective therapies and steroid-sparing regimens may reduce organ damage, improve outcomes and decrease mortality for patients with SLE.


2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Yu Fu ◽  
Qing Lin ◽  
Zhi-rong Zhang

Abstract Objective To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a meta-analysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265. Methods A literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI). Results The meta-analysis produced overall OR of 1.42 (95% CI 1.36–1.49, P < 0.00001), 1.41 (95% CI 1.36–1.46, P < 0.00001) and 1.34 (95% CI 1.26–1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70–1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86–1.43, P = 0.41) or rs10489265 (OR 1.17, 95% CI 0.94–1.47, P = 0.17) polymorphism with SLE susceptibility, respectively. Conclusions Our meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.


Lupus ◽  
2020 ◽  
pp. 096120332097408
Author(s):  
Zhao Jin ◽  
Cong Yang ◽  
Chu Xiao ◽  
Zizhen Wang ◽  
Suxin Zhang ◽  
...  

Objective To systematically review and summarize the available literature regarding the association between systemic lupus erythematosus (SLE) and sexual dysfunction (SD) in both sexes. Methods We retrieved relevant studies from the following databases: PubMed, Embase, Cochrane Library, and Web of Science. Two reviewers independently reviewed the studies in our sample, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results Our search resulted in a sample of eight eligible studies, which involved 758 patients in the SLE group and 1724 individuals in the control group. The pooled RR for the increased risk for SD compared to those in the control group was 1.80 (95%CI 1.12-2.87). Subgroup analysis by sex revealed that males (pooled RR = 2.98, 95%CI 2.41-3.68) had a higher risk of SD compared to females (pooled RR = 1.56, 95%CI 0.99-2.48). Females with SLE had significantly lower values in FSFI compared to the healthy individuals (WMD=-0.224, 95%CI -0.441 to -0.078). Age of participants and the quality of studies might influence the results. Conclusions Our meta-analysis suggests that SLE is significantly associated with an increased risk of sexual dysfunction. It is of great urgency to implement for active interventions that aimed to treat or prevent SD among SLE patients.


Author(s):  
Xiaolan Huang ◽  
Nan Jia ◽  
Fei Xiao ◽  
Chunrong Sun ◽  
Jia Zhu ◽  
...  

<b><i>Introduction:</i></b> The aim of this study was to assess the differences between childhood-onset and adult-onset systemic lupus erythematosus (cSLE and aSLE) for clinical manifestations and mortality using a meta-analytic approach. <b><i>Methods:</i></b> The PubMed, EMBASE, and the Cochrane library were searched for eligible studies published between January 1982 and March 2021. The odds ratio (OR) with 95% confidence interval was used to calculate the pooled effect estimates using the random-effects model. <b><i>Results:</i></b> Thirty-four studies involving 21,946 SLE patients were included. cSLE was associated with an increased risk of malar rash (OR: 1.64; <i>p</i> &#x3c; 0.001), ulcers/mucocutaneous involvement (OR: 1.22; <i>p</i> = 0.039), general neurological involvement (OR: 1.52; <i>p</i> &#x3c; 0.001), seizures (OR: 1.92; <i>p</i> &#x3c; 0.001), general renal involvement (OR: 2.08; <i>p</i> &#x3c; 0.001), proteinuria (OR: 1.35; <i>p</i> = 0.015), urinary cellular casts (OR: 1.67; <i>p</i> = 0.047), fever (OR: 2.31; <i>p</i> &#x3c; 0.001), anemia (OR: 1.91; <i>p</i> &#x3c; 0.001), thrombocytopenia (OR: 1.41; <i>p</i> &#x3c; 0.001), leucopenia (OR: 1.57; <i>p</i> = 0.017), lymphadenopathy (OR: 2.40; <i>p</i> &#x3c; 0.001), and cutaneous vasculitis (OR: 1.72; <i>p</i> = 0.001) as compared with aSLE. Moreover, cSLE versus aSLE was associated with a reduced risk of articular manifestations (OR: 0.63; <i>p</i> = 0.001), pulmonary involvement (OR: 0.54; <i>p</i> = 0.001), and pleuritis (OR: 0.61; <i>p</i> &#x3c; 0.001). There were no significant differences between cSLE and aSLE for mortality risk (OR: 1.20; <i>p</i> = 0.203). <b><i>Conclusion:</i></b> We found that certain clinical manifestations of SLE are different in cSLE and aSLE. Moreover, the mortality risk of cSLE and aSLE was not significantly different.


Lupus ◽  
2020 ◽  
Vol 29 (12) ◽  
pp. 1556-1565
Author(s):  
Leyre Riancho-Zarrabeitia ◽  
Victor Martínez-Taboada ◽  
Iñigo Rúa-Figueroa ◽  
Fernando Alonso ◽  
María Galindo-Izquierdo ◽  
...  

Introduction Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Materials and methods Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. Results We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups ( p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p  < 0.001). SLE-APS patients showed higher mortality rates ( p < 0.001). Conclusions SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.


2018 ◽  
Vol 45 (10) ◽  
pp. 1448-1461 ◽  
Author(s):  
Stephanie O. Keeling ◽  
Ben Vandermeer ◽  
Jorge Medina ◽  
Trish Chatterley ◽  
Tatiana Nevskaya ◽  
...  

Objective.To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations.Methods.Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for “minimal investigations needed to monitor SLE patients at baseline and subsequent visits,” a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available.Results.A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06–1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28–1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04–1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15.Conclusion.Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.


2018 ◽  
Vol 12 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Zhuoxian Zhao ◽  
Natalia P. Rocha ◽  
Haitham Salem ◽  
Breno S. Diniz ◽  
Antonio L. Teixeira

Abstract A growing body of evidence indicates that systemic lupus erythematosus (SLE) is associated with increased risk of cognitive impairment and dementia. However, to date, no studies have been conducted to quantitatively summarize and evaluate the consistency of data. Objective: To quantitatively evaluate the relationship of SLE and antiphospholipid antibodies (aPL) with cognitive dysfunction and dementia. Methods: All relevant literature was retrieved from Pubmed, Scopus, and PsycINFO databases. The meta-analysis was performed using effect estimates and 95% confidence intervals (CIs) to calculate pooled risk estimates. The heterogeneity among studies was also examined. Results: The meta-analysis included 11 original studies involving a total of 81,668 patients with dementia and 407 patients with cognitive dysfunction. There were significant associations on fixed-effect models between SLE and dementia (3 studies; RR=1.50; 95% CI=1.37-1.64), SLE and cognitive dysfunction (4 studies; OR=2.97; 95% CI=1.72-5.15), and aPL and cognitive dysfunction (5 studies, OR=1.97; 95% CI=1.55-2.52). We also combined cognitive dysfunction and dementia outcomes as they both represented cognitive impairment. There were significant associations between aPL and cognitive impairment (6 studies; OR=2.03; 95% CI=1.62-2.55), and SLE and cognitive impairment (7 studies; OR=1.83; 95% CI=1.42-2.35). Moderate heterogeneity (I2=45.7%) was found in the association between SLE and cognitive impairment, low heterogeneity (I2=21.8%) in the association between SLE and dementia, and near zero heterogeneity for the other three main analyses. Conclusion: Both SLE and aPL are associated with cognitive impairment.


Lupus ◽  
2017 ◽  
Vol 27 (3) ◽  
pp. 428-435 ◽  
Author(s):  
Y H Lee ◽  
G G Song

Objective We aimed to evaluate the relationship between circulating leptin levels and systemic lupus erythematosus (SLE). Methods MEDLINE, EMBASE, and Cochrane library databases were searched. Meta-analyses were performed comparing serum/plasma leptin levels in patients with SLE and healthy controls, and on patients with SLE in subgroups based on ethnicity, sample size, data type, and matched variables (age, sex, and/or body mass index (BMI)). Results Eighteen studies including 1333 patients with SLE and 1048 controls were ultimately selected, which showed that leptin levels were significantly higher in the SLE group than in the control group (SMD = 0.611, 95% CI = 0.275–0.947, p < 0.001). When we excluded two outlier studies because of high heterogeneity, leptin levels were also significantly higher in the SLE group than in the control group (SMD = 0.619, 95% CI = 0.431–0.807, p < 0.001). Stratification by ethnicity showed significantly elevated leptin levels in the SLE group in European, Asian, Arab, Latin American, and mixed populations. Subgroup analysis by sample size showed significantly higher leptin levels in the SLE group by small ( n ≤ 100) and large sample numbers ( n > 100) (SMD = 0.780, 95% CI = 0.445–1.115, p < 0.001; SMD = 0.495, 95% CI = 0.275–0.715, p < 0.001). Stratification by data type revealed significantly higher leptin levels in the original data and imputed data groups. Subgroup analysis adjustment revealed significantly higher leptin levels in the SLE group, regardless of adjustment for variables. Conclusions Our meta-analysis demonstrated that leptin levels were significantly higher in patients with SLE, regardless of ethnicity, sample size, data type, and matched variables.


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