Efficacy and safety of rituximab on lung and skin involvement in systemic sclerosis: a systematic review and metaanalysis

Clinical Rheumatology - To evaluate the efficacy and safety of rituximab (RTX), an antiB cell monoclonal antibody, on lung and skin involvement in systemic sclerosis (SSc). All literature published...     

Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis

BackgroundType I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment.MethodsThe MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates.ResultsSeven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5–93.9) with no heterogeneity (I² = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5–40.3) with moderate heterogeneity (I² = 51%). A higher rate of relapse (35.9%, 95%CI 17.3–60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8–53) with substantial heterogeneity (I² = 73.6%). No publication bias was observed.ConclusionTreatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.     

Risk of coronary artery disease in patients with systemic sclerosis: a systematic review and meta-analysis

Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, have been shown to increase coronary artery disease (CAD) risk but the data on systemic sclerosis (SSc) is unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing CAD risk in patients with SSc versus non-SSc participants. Pooled risk ratio and 95 % confidence intervals were calculated using a random effect, generic inverse variance method. Four studies were identified and included in our data analysis. The pooled risk ratio of CAD in patients with SSc was 1.82 (95 % CI, 1.40 to 2.36). The statistical heterogeneity of this meta-analysis was moderate with an I ² of 73 %. Our study demonstrated a statistically significant increased CAD risk among patients with SSc.     

Isoprostane in systemic sclerosis: A systematic review and meta-analysis

Abstract

Objectives: To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc.

Methods: Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma.

Results: After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p?<?.001) with wide heterogeneity (I²?=?75%). Subgroup analysis on urinary isoprostane favoured excess excretion in SSc (p?=?.009) with slightly lower heterogeneity (I²?=?67%); further subgroup analysis according to unit of measurement revealed no increased isoprostane excretion when expressed as pg/mg creatinine but increased when expressed as pmol/mmol creatinine (p?=?.05) with medium heterogeneity (I²?=?32%). Subgroup analysis on serum isoprostane favoured overproduction in SSc (p?<?.0001) with no heterogeneity.

Conclusion: There is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker.     

Risk of ischemic stroke in patients with systemic sclerosis: A systematic review and meta-analysis

Background. Several chronic inflammatory disorders, such as rheumatoid arthritis and idiopathic inflammatory myositis, have been shown to increase risk of ischemic stroke but the data on systemic sclerosis (SSc) remains unclear.

Methods. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of ischemic stroke in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.

Results. Four retrospective cohort studies were identified and included in our data analysis. We found a statistically significant elevated ischemic stroke risk in patients with SSc with a pooled risk ratio of 1.68 (95% CI, 1.26–2.24). The statistical heterogeneity was moderate with an I² of 69%.

Conclusions. Our study demonstrated a statistically significant increased ischemic stroke risk among patients with SSc.     

Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: A systematic review

Objective

To analyse the efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus (SLE).

Methods

We systematically searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials up to June 2013. The following were the selection criteria: (1) adult patients with SLE, (2) rituximab treatment, (3) placebo or active comparator, (4) outcome measures assessing efficacy and/or (5) safety. Meta-analysis, systematic literature reviews, randomised control trials (RCT), open clinical trials and cohort studies were included.Independent extraction of articles by 2 authors using predefined data fields was performed. The quality of each study was graded using the Oxford Levels of Evidence and Jadad?s scale.

Results

A total of 26 articles met our inclusion criteria: one RCT and its exploratory analysis, 2 open studies and 22 cohort studies, which analysed 1,231 patients. Overall, patients had active disease refractory to steroids and/or immunosuppressant drugs. Acceptable evidence suggested improvements in disease activity, arthritis, thrombocytopaenia, complement and anti-dsDNA, with a steroid-sparing effect. But relapses of disease were demonstrated too. Weak evidence suggested a response in anaemia, cutaneous and neuropsychiatric manifestations. Available evidence revealed few major adverse events. Studies had medium methodological quality and in general were applicable to current practice.

Conclusion

Rituximab has been shown to be safe and effective in the treatment of non-renal SLE, especially in terms of disease activity, immunologic parameters and steroid-sparing effect. However, it can only be recommended for organ-specific manifestations such as arthritis and thrombocytopaenia. High-quality studies are needed in order to consider the long-term effects of re-treatment on different organ-specific manifestations.     

Clinical significance of soluble CD31 in patients with systemic sclerosis (SSc): association with limited cutaneous SSc.

OBJECTIVE: To determine serum levels of soluble CD31 (sCD31) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum sCD31 levels from 70 patients with SSc were examined by ELISA. For a longitudinal study, 64 sera from 17 SSc patients were analyzed (followup: 0.4-3.9 yrs). RESULTS: Serum sCD31 levels were elevated in patients with SSc (n = 70) compared with healthy controls (n = 20) and patients with systemic lupus erythematosus (n = 15). Serum sCD31 levels were higher in patients with limited cutaneous SSc (lSSc; n = 37) than those with diffuse cutaneous SSc (n = 33). Patients with elevated sCD31 levels had pulmonary fibrosis and decreased percentage vital capacity (%VC) less frequently than those with normal sCD31 levels. sCD31 levels correlated positively with %VC in patients with SSc. This association of elevated sCD31 levels with the lower frequency of pulmonary involvement and better %VC was still observed when analyzed among ISSc patients alone. The elevation of sCD31 was associated with shorter disease duration in patients with lSSc. In a longitudinal study, 75% of patients with SSc showed increased sCD31 levels only transiently in the early phase of the disease. Serum sCD31 levels remained normal during followup in all patients with normal sCD31 levels at the first visit. CONCLUSION: Elevated sCD31 levels were associated with ISSc with relatively early onset and lower frequency and severity of pulmonary fibrosis. These results suggest that sCD31 would be a protective factor for the development of skin sclerosis and pulmonary fibrosis in SSc, since sCD31 has an antiinflammatory effect by inhibiting CD31 mediated transendothelial migration of leukocytes.     

Assessing dyspnea-related kinesiophobia in patients with systemic sclerosis (SSc): validity and reliability of Turkish Breathlessness Beliefs Questionnaire for SSc

Clinical Rheumatology - The respiratory system is often affected by systemic sclerosis (SSc), a connective tissue disease characterized by fibrosis, vasculopathy, and inflammation. As a result,...     

Efficacy and safety evaluation of acupuncture therapy for patients with salpingitis in IVF-ET: A protocol of systematic review and meta-analysis

Background:As an alternative for salpingitis in IVF-ET, acupuncture has gradually attracted the attention of clinicians based on the theory of syndrome differentiation and treatment of Chinese traditional medicine. However, due to the lack of evidence-based medical evidence, the author designed the program to evaluate the effectiveness and safety of acupuncture.Methods:From the beginning to August 2020, 7 electronic databases will be searched. Two of our researchers will independently conduct research selection, data extraction, and risk assessment of bias. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. In addition, we will use the grading of recommendations assessment, development, and evaluation to evaluate the evidence quality.Results:This study will demonstrate an evidence-based review of acupuncture for salpingitis in IVF-ET.Conclusion:The study will provide clear evidence to assess the effectiveness and side effects of acupuncture for salpingitis in IVF-ET.Trial registration number:INPLASY2020110125.     

Efficacy and safety evaluation of bright light therapy in patients with post-stroke insomnia: A protocol for systematic review and meta-analysis

Background:Post-stroke insomnia (PSI) is a common and severe illness among the complications of stroke. Although there are plenty of drugs currently used for PSI treatment, they generate several side effects and other problems. Bright light therapy (BLT) is thought to be relatively safe and effective in treating PSI patients. Despite this, there is still a lack of systematic review on BLT in the treatment of PSI. Allowing for this, the aim of this study is to assess the efficacy and safety of BLT for PSI.Methods:The meta-analysis and systematic review will perform a comprehensive electronic search for items fulfilling the required criteria in Web of Science, Google Scholar, Wan Fang database, MEDLINE, Baidu Scholar, PubMed, SinoMed, Embase, Chinese Biomedical Literature Database (CBM), China national knowledge infrastructure database (CNKI), Cochrane Library Central Register of Controlled Trials (CENTRAL), and Wei Pu database from establishment to January 1, 2022. We will select articles, collect data, and assess the methodology quality. And we will set the primary outcome and secondary outcomes in this research. RevMan 5.3 software will be used to analyze the data for this investigation.Results:The work of this research will be published in peer-reviewed scientific journals.Conclusion:The aim of this study is to assess the efficacy and safety of BLT for PSI and present robust scientific evidence concerning BLT for PSI.Registration:INPLASY2021100065.     

Efficacy and safety of cefepime: a systematic review and meta-analysis

Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram-positive and Gram-negative bacteria. We did a systematic review of randomised trials that compared cefepime with another beta-lactam antibiotic, alone or with the addition of a non-beta-lactam antibiotic to both study groups. We searched Central, PubMed, Embase, Lilacs, new US Food and Drug Administration drug applications, conference proceedings, and references of the included studies. Two reviewers independently did the search and data extraction. 57 trials were included. All-cause mortality-the primary outcome-was higher with cefepime than other beta-lactams (risk ratio [RR] 1.26 [95% CI 1.08-1.49]). Sensitivity analyses by the trials' methodological quality revealed higher RRs for trials reporting adequate allocation-sequence generation (1.52 [1.20-1.92]) and allocation concealment (1.36 [1.09-1.70]). Baseline risk factors for mortality were similar. No significant differences between groups in treatment failure, superinfection, or adverse events were found. This Review provides evidence and offers possible explanations for increased mortality among patients treated with cefepime in randomised trials.     

Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

AimsIndividuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.Data synthesisWe performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: −1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: −0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).ConclusionsPCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.Registration code in prosperoCRD42022339785.     

Efficacy and safety evaluation of hyperbaric oxygen therapy for patients with ulcerative colitis: A protocol of systematic review and meta-analysis

Background:Ulcerative colitis (UC) belongs to chronic colitis whose etiology and pathogenesis still have remained unclear. Hyperbaric oxygen therapy (HBOT) has been demonstrated to be effective for UC therapy. Still, evidence of its efficacy and safety is inconclusive. The purpose of the protocol is to evaluate the efficacy and safety of HBOT in UC therapy.Methods:This systematic review will retrieve studies that meet the requirements in Embase, MEDLINE, PubMed, Web of Science, Cochrane Library Central Register of Controlled Trials, the Chinese Biomedical Literature Database (CBM), China national knowledge infrastructure database (CNKI), Wei Pu database, Wan fang database, SinoMed, Google scholar, and Baidu Scholar from their inception to November 2020. Two authors are to be independent in their article selection, data collection, and research quality assessments. The primary outcome is the clinical effectiveness. And the secondary outcomes will include 4 criteria. RevMan 5.3 software will be utilized for analysis of the data.Results:The results of this study are to be submitted via a peer-reviewed journal.Conclusions:The study is to assess the effectiveness and safety of HBOT for UC and provide valid and reliable evidence regarding HBOT for UC.INPLASY registration number:INPLASY2020100118.     

Efficacy and safety of valproic acid in dementia: A systematic review with meta-analysis

IntroductionThe neuroprotective effect of valproic acid has been observed in the animal models of neurodegeneration, which suggests it as a potential candidate for clinical trials. In this paper, we aimed to systematically analyze the efficacy and safety of valproic acid in the treatment of dementia.MethodsWe searched the electronic databases PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure until March 2020 for the eligible randomized controlled trials, as well as the unpublished and ongoing trials. We pooled the results using a random-effects model.ResultsWe included seven studies with 770 randomized patients with dementia, which compared valproic acid with placebo. Indeed, there were no significant differences found in the scores of Mini–mental State Examination, Cohen-Mansfield Agitation Inventory and number of patients with adverse events. Valproic acid is generally well-tolerated in patients with dementia, even in long-term therapy for 24 months.ConclusionInsufficient evidences are found to support valproic acid in the treatment of dementia for cognitive, psychiatric symptoms or disease-modifying. The anticipations for a success in the trial of valproic acid for dementia in the future look not optimistic based on the available evidence.