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Arthritis Research & Therapy Jul 2023The objective of this systematic review was to assess the effects of interleukin-1β (IL-1β) inhibitors on gout flares. (Review)
Review
OBJECTIVES
The objective of this systematic review was to assess the effects of interleukin-1β (IL-1β) inhibitors on gout flares.
METHODS
Studies published between 2011 and 2022 that evaluated the effects of IL-1β inhibitors in adult patients experiencing gout flares were eligible for inclusion. Outcomes including pain, frequency and intensity of gout flares, inflammation, and safety were assessed. Five electronic databases (Pubmed/Medline, Embase, Biosis/Ovid, Web of Science and Cochrane Library) were searched. Two independent reviewers performed study screening, data extraction and risk of bias assessments (Cochrane Risk of Bias Tool 2 for randomised controlled trials [RCTs] and Downs and Black for non-RCTs). Data are reported as a narrative synthesis.
RESULTS
Fourteen studies (10 RCTs) met the inclusion criteria, with canakinumab, anakinra, and rilonacept being the three included IL-1β inhibitors. A total of 4367 patients with a history of gout were included from the 14 studies (N = 3446, RCTs; N = 159, retrospective studies [with a history of gout]; N = 762, post hoc analysis [with a history of gout]). In the RCTs, canakinumab and rilonacept were reported to have a better response compared to an active comparator for resolving pain, while anakinra appeared to be not inferior to an active comparator for resolving pain. Furthermore, canakinumab and rilonacept reduced the frequency of gout flares compared to the comparators. All three medications were mostly well-tolerated compared to their comparators.
CONCLUSION
IL-1β inhibitors may be a beneficial and safe medication for patients experiencing gout flares for whom current standard therapies are unsuitable.
REVIEW PROTOCOL REGISTRATION
PROSPERO ID: CRD42021267670.
Topics: Adult; Humans; Interleukin Inhibitors; Interleukin-1beta; Interleukin 1 Receptor Antagonist Protein; Gout; Arthritis, Gouty
PubMed: 37491293
DOI: 10.1186/s13075-023-03098-4 -
Pharmacological Research Sep 2023To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis.
RESULTS
A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events.
CONCLUSION
TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.
Topics: Humans; Glucosides; Tumor Necrosis Factor-alpha; Paeonia; Arthritis, Psoriatic; Arthritis, Rheumatoid
PubMed: 37402434
DOI: 10.1016/j.phrs.2023.106842 -
International Journal of Molecular... Jun 2023Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been... (Meta-Analysis)
Meta-Analysis Review
Diverticular disease (DD) is the most frequent condition in the Western world that affects the colon. Although chronic mild inflammatory processes have recently been proposed as a central factor in DD, limited information is currently available regarding the role of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Therefore, we conducted a systematic review and meta-analysis aiming to assess the mucosal TNF-α levels in DD. We conducted a systematic literature search using PubMed, Embase, and Scopus to identify observational studies assessing the TNF-α levels in DD. Full-text articles that satisfied our inclusion and exclusion criteria were included, and a quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The principal summary outcome was the mean difference (MD). The results were reported as MD (95% confidence interval (CI)). A total of 12 articles involving 883 subjects were included in the qualitative synthesis, out of which 6 studies were included in our quantitative synthesis. We did not observe statistical significance related to the mucosal TNF-α levels in symptomatic uncomplicated diverticular disease (SUDD) vs. the controls (0.517 (95% CI -1.148-2.182)), and symptomatic vs. asymptomatic DD patients (0.657 (95% CI -0.883-2.196)). However, the TNF-α levels were found to be significantly increased in DD compared to irritable bowel disease (IBS) patients (27.368 (95% CI 23.744-30.992)), and segmental colitis associated with diverticulosis (SCAD) vs. IBS patients (25.303 (95% CI 19.823-30.784)). Between SUDD and the controls, as well as symptomatic and asymptomatic DD, there were no significant differences in the mucosal TNF-α levels. However, the TNF-α levels were considerably higher in DD and SCAD patients than IBS patients. Our findings suggest that TNF-α may play a key role in the pathogenesis of DD in specific subgroups and could potentially be a target for future therapies.
Topics: Humans; Tumor Necrosis Factor-alpha; Irritable Bowel Syndrome; Colitis; Inflammation; Diverticular Diseases
PubMed: 37373082
DOI: 10.3390/ijms24129934 -
Exercise Immunology Review 2023In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown.
OBJECTIVES
The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients.
METHODS
PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-tools.
RESULTS
Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-α (MD: -0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree of evidence was found for a decrease in IL-6 (ES:-0.596 & -0.259 & -0.513), an increase in sTNFR1 (ES:2.325), a decrease in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1β (ES:-6.199) and TNF-α decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-α:-0.019 & 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data).
CONCLUSION
ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET.
Topics: Humans; Osteoarthritis, Knee; Brain-Derived Neurotrophic Factor; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-6; Biomarkers
PubMed: 37358362
DOI: No ID Found -
Medicine Jun 2023Vascular dementia is a cognitive dysfunction syndrome caused by cerebral vascular factors such as ischemic stroke and hemorrhagic stroke. The effect of acupuncture on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular dementia is a cognitive dysfunction syndrome caused by cerebral vascular factors such as ischemic stroke and hemorrhagic stroke. The effect of acupuncture on vascular dementia models is ambiguous, and there is controversy about whether acupuncture has a placebo effect. Oxidative stress and inflammation are the most essential mechanisms in preclinical studies of vascular dementia. However, there is no meta-analysis on the mechanism of vascular dementia in animal models. It is necessary to explore the efficacy of acupuncture through Meta-analysis of preclinical studies.
METHODS
Three major databases, PubMed, Embase and Web of Science (including medline), were searched in English until December 2022.The quality of the including literature was assessed using SYRCLE's risk of bias tool. Review Manager 5.3 was used to statistically summarize the included studies and the statistical effect values were expressed by SMD. The outcomes included: behavioral tests (escape latency, number of crossings), pathological sections (Nissl and TUNEL staining), oxidative stress markers (ROS, MDA, SOD, GSH-PX) and neuroinflammatory factors (TNF-α, IL-1β, IL-6).
RESULTS
A total of 31 articles were included in this meta-analysis. The results showed that the escape latency, the contents of ROS, MDA, IL-1β, and IL-6 were decreased, and the contents of SOD and Nissl-positive neurons were increased in the acupuncture group as compared with the non-group (P < .05). Compared with the impaired group, the acupuncture group also had the above advantages (P < .05). In addition, the acupuncture group also increased the number of crossings and GSH-PX content, and decreased the expression of TUNEL-positive neurons and TNF-α (P < .05).
CONCLUSIONS
From behavioral tests to slices and pathological markers in animal models of vascular dementia, it can be proved that acupuncture is effective in targeting oxidative stress and neuroinflammatory damage, and acupuncture is not a placebo effect. Nevertheless, attention needs to be paid to the gap between animal experiments and clinical applications.
Topics: Animals; Dementia, Vascular; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Interleukin-6; Acupuncture Therapy; Oxidative Stress; Disease Models, Animal; Superoxide Dismutase
PubMed: 37335660
DOI: 10.1097/MD.0000000000033989 -
Frontiers in Immunology 2023Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease.
OBJECTIVE
We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE.
METHODS
We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15 September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger's test.
RESULTS
Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels.
CONCLUSION
Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.
Topics: Humans; Female; Pregnancy; Infant; Interleukin-10; Pre-Eclampsia; Interleukin-6; Interleukin-8; Cytokines; Biomarkers; Tumor Necrosis Factor-alpha; C-Reactive Protein
PubMed: 37325643
DOI: 10.3389/fimmu.2023.1156039 -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
BMC Ophthalmology May 2023To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU).
METHODS
We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated.
RESULTS
Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab.
CONCLUSION
Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.
Topics: Humans; Adalimumab; Infliximab; Antibodies, Monoclonal; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Uveitis; Inflammation
PubMed: 37248486
DOI: 10.1186/s12886-023-02987-1 -
The Journal of International Medical... May 2023To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To study the effectiveness of infliximab for the treatment of refractory central neuro-Behçet's disease.
METHODS
In this systematic review and meta-analysis, the research question was designed using the 'Population, Intervention, Comparator, and Outcomes' (PICO) model and the search methodology was developed according to the PRISMA statement. The study was registered on PROSPERO. Web of Science, PubMed, and Cochrane Library databases were searched for articles published in English between January 2000 and January 2020. Data were analysed using Meta-Essentials software, version 10.12. Treatment effect size was determined by a random effects model. Interstudy heterogeneity was explored using I statistics. Cumulative meta-analysis was conducted to assess the temporal trend for accumulating evidence.
RESULTS
Twenty-one studies, comprising 64 patients (mean age, 38 .21 years and mean disease duration, 84.76 months) were included. Effect-size analysis showed that 93.7% of the treated patients in the analysis were responders to infliximab therapy (95% confidence interval 0.88, 0.993). There was no significant inter-study heterogeneity (I = 0%). Cumulative analysis showed accumulating evidence favoring increasing effectiveness over the last 20 years.
CONCLUSION
Infliximab showed considerable therapeutic effectiveness in the treatment of refractory neuro-Behçet's disease.
Topics: Humans; Adult; Infliximab; Behcet Syndrome; Antibodies, Monoclonal; Tumor Necrosis Factor-alpha; Necrosis
PubMed: 37203384
DOI: 10.1177/03000605231169895 -
Annals of Medicine Dec 2023This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19.
METHODS
The PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library databases were searched for relevant articles from their inception to 25 September 2022. Only randomized clinical trials (RCTs) that assessed the clinical efficacy and safety of IL-1 blockade in the treatment of patients with COVID-19 were included.
RESULTS
This meta-analysis included seven RCTs. No significant difference in the all-cause mortality rate of patients with COVID-19 was observed between the IL-1 blockade and control groups (7.7 vs. 10.5%, odds ratio [OR] = 0.83, 95% confidence interval [CI] 0.57-1.22; = 18%). However, the study group was at significantly lower risk of requiring mechanical ventilation (MV) compared with the control group (OR = 0.53, 95% CI 0.32-0.86; = 24%). Finally, the risk of adverse events was similar between the two groups.
CONCLUSIONS
IL-1 blockade does not provide increased survival benefits in hospitalized patients with COVID-19, but it may reduce the need for MV. Furthermore, it is a safe agent for use in the treatment of COVID-19.>.
Topics: Humans; COVID-19; Interleukin-1; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 37199379
DOI: 10.1080/07853890.2023.2208872