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Cureus Feb 2023Axial spondylarthritis (axSpA) is a progressive inflammatory condition that is treated with various management options. Interleukin-17A (IL-17A) inhibitors are a novel... (Review)
Review
Axial spondylarthritis (axSpA) is a progressive inflammatory condition that is treated with various management options. Interleukin-17A (IL-17A) inhibitors are a novel therapeutic option that demonstrates both efficacy and safety. This systematic review and meta-analysis evaluated the effectiveness of ixekizumab and its safety compared to a placebo. Medline, ScienceDirect, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched. We included randomized control trials (RCTs) that assessed the efficacy and safety of ixekizumab versus the placebo. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) assessment was utilized to evaluate the certainty of evidence. The revised Cochrane risk of bias tool for randomized trials was used to assess the risk of bias. Four RCTs (n=1016) met the eligibility criteria. All included studies had a low risk of bias. Significant improvements in the Assessment of Spondylarthritis International Society response for 40% improvement (ASAS40) (RR = 2.39, 95% CI 1.72-3.31, P < 0.01, I2 = 23%), Ankylosing Spondylitis Disease Activity Score (ASDAS) (SMD= -9.28 95% CI -12.31- (-6.25), P < 0.01, I2=97%), and Spondylarthritis Research Consortium of Canada (SPRACC score) (SMD= -5.82 95% CI -7.16- (-4.47), P < 0.01, I2=94%) were noted in comparison to placebo. Regarding safety, there was an insignificant increase in risk for serious adverse events (SAEs) (RR = 1.19, 95% CI 0.45-3.14, P = 0.73, I2 = 0%). Additionally, significant nonserious adverse events (NSAEs) (RR = 1.54, 95% CI 1.19-1.99, P = 0.001, I2 = 0%) were noted for the ixekizumab arm. No mortality events were detected in both arms. Ixekizumab, which demonstrates significant improvement in all efficacy endpoints, is a promising management option for axSpA patients who fail non-steroidal anti-inflammatory drugs (NSAIDs) therapy. However, the significant risk of developing adverse events hinders its utilization. More high-quality RCTs with larger sample sizes and prolonged follow-up periods are warranted to further assess this treatment option.
PubMed: 36974243
DOI: 10.7759/cureus.35360 -
Frontiers in Immunology 2023To explore the efficacy and safety of Iguratimod (IGU) intervention in the treatment of Ankylosing Spondylitis (AS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the efficacy and safety of Iguratimod (IGU) intervention in the treatment of Ankylosing Spondylitis (AS).
METHODS
We used computer to search literature databases, collected randomized controlled trials (RCTs) related to IGU treatment of AS, and searched the relevant literature in each database until Sep. 2022. Two researchers independently carried out literature screening, data extraction, and evaluation and analysis of the risk of bias in the included studies, and then used Rev Man5.3 software for meta-analysis. The protocol is CRD42020220798.
RESULTS
A total of 10 RCTs involves in 622 patients were collected. The statistical analysis showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], P<0.00001. Quality of evidence: low), the BASFI score (WMD -1.30 [-1.48, -1.12], P<0.00001. Quality of evidence: low) and the VAS (WMD -2.01 [-2.83, -1.19], P<0.00001. Quality of evidence: very low). Meanwhile, the addition of IGU into the conventional therapy would not increase the adverse events (RR 0.65 [0.43, 0.98], P=0.04. Quality of evidence: moderate).
CONCLUSION
IGU may be an effective and safe intervention for AS.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220798.
Topics: Humans; Spondylitis, Ankylosing; Randomized Controlled Trials as Topic; Sulfonamides; Chromones
PubMed: 36936924
DOI: 10.3389/fimmu.2023.993860 -
Annals of Translational Medicine Feb 2023Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable....
Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.
BACKGROUND
Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS.
METHODS
We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses.
RESULTS
We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70).
CONCLUSIONS
TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.
PubMed: 36923085
DOI: 10.21037/atm-23-195 -
Reumatologia Clinica Mar 2023Ankylosing spondylitis is a chronic inflammatory disease that is associated with adverse cardiovascular events. This study aimed to determine the relationship between... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ankylosing spondylitis is a chronic inflammatory disease that is associated with adverse cardiovascular events. This study aimed to determine the relationship between ankylosing spondylitis and the risk of stroke.
METHODS
A systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science were conducted from inception to December 2021 to identify relevant articles investigating the risk of stroke in patients with ankylosing spondylitis. A random-effects model (DerSimonian and Laird) was used to estimate a pooled hazard ratio (HR) and 95% confidence intervals (CI). Meta-regression based on the length of follow-up and subgroup analysis based on the type of stroke, study location, and year of publication to investigate the source of heterogeneity.
RESULTS
A total of eleven studies comprising 1.7 million participants were included in this study. Pooled analysis showed a significantly increased stroke risk (56%) among patients with ankylosing spondylitis (HR: 1.56, 95% CI 1.33-1.79). Subgroup analysis revealed a higher risk of ischemic stroke among patients with ankylosing spondylitis (HR: 1.46, 95% CI: 1.23-1.68). However, meta-regression analysis showed no association between the duration of ankylosing spondylitis and stroke incidence (Coef=-0.0010, P=0.951).
CONCLUSION
This study reveals that ankylosing spondylitis was associated with an increased risk of suffering a stroke. Management of cerebrovascular risk factors and the control of systemic inflammation should be considered in patients with ankylosing spondylitis.
Topics: Humans; Spondylitis, Ankylosing; Risk Factors
PubMed: 36906389
DOI: 10.1016/j.reumae.2023.02.002 -
Frontiers in Pharmacology 2023Tumor necrosis factor alpha inhibitors (TNFi) have shown substantial efficacy in alleviating and treating ankylosing spondylitis (AS). However, the heightened interest...
Tumor necrosis factor alpha inhibitors (TNFi) have shown substantial efficacy in alleviating and treating ankylosing spondylitis (AS). However, the heightened interest is accompanied by concerns over adverse events. In this meta-analysis, we analyzed both serious and common adverse events in patients treated with tumor necrosis factor alpha inhibitors compared with those in the placebo group. We searched for clinical trials in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and VIP Data. Studies were selected based on strict inclusion and exclusion criteria. Only randomized, placebo-controlled trials were included in the final analysis. RevMan 5.4 software was used for performing meta-analyses. A total of 18 randomized controlled trials recruiting 3,564 patients with ankylosing spondylitis were included, with overall moderate to high methodological quality. Compared with the placebo group, the incidences showed no difference and were only slightly increased numerically for serious adverse events, serious infections, upper respiratory tract infection, and malignancies in patients treated with tumor necrosis factor alpha inhibitors. However, tumor necrosis factor alpha inhibitor treatment significantly increased the incidence of overall adverse events, nasopharyngitis, headache, and injection-site reactions in ankylosing spondylitis patients when compared with placebo. The available data indicated that ankylosing spondylitis patients who received tumor necrosis factor alpha inhibitors had no significantly increased risks of serious adverse events when compared with the placebo group. However, tumor necrosis factor alpha inhibitors significantly increased the incidence rate of common adverse events, including nasopharyngitis, headache, and injection-site reactions. Large-scale and long-term follow-up clinical trials are still necessary to further investigate the safety of tumor necrosis factor alpha inhibitors in ankylosing spondylitis treatment.
PubMed: 36865909
DOI: 10.3389/fphar.2023.1084614 -
RMD Open Mar 2023To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the... (Review)
Review
Points to consider for cost-effective use of biological and targeted synthetic DMARDs in inflammatory rheumatic diseases: results from an umbrella review and international Delphi study.
OBJECTIVES
To develop evidence-based points to consider for cost-effective use of biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the treatment of inflammatory rheumatic diseases, specifically rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis.
METHODS
Following EULAR procedures, an international task force was formed, consisting of 13 experts in rheumatology, epidemiology and pharmacology from seven European countries. Twelve strategies for cost-effective use of b/tsDMARDs were identified through individual and group discussion. For each strategy, PubMed and Embase were systematically searched for relevant English-language systematic reviews and, for six strategies, additionally for randomised controlled trials (RCTs). Thirty systematic reviews and 21 RCTs were included. Based on the evidence, a set of overarching principles and points to consider was formulated by the task force using a Delphi procedure. Level of evidence (1a-5) and grade (A-D) were determined for each point to consider. Individual voting on the level of agreement (LoA; between 0 (completely disagree) and 10 (completely agree)) was performed anonymously.
RESULTS
The task force agreed on five overarching principles. For 10 of 12 strategies, the evidence was sufficient to formulate one or more points to consider, leading to 20 in total, regarding response prediction, drug formulary use, biosimilars, loading doses, low-dose initial therapy, concomitant conventional synthetic DMARD use, route of administration, medication adherence, disease activity-guided dose optimisation and non-medical drug switching. Ten points to consider (50%) were supported by level 1 or 2 evidence. The mean LoA (SD) varied between 7.9 (1.2) and 9.8 (0.4).
CONCLUSION
These points to consider can be used in rheumatology practices and complement inflammatory rheumatic disease treatment guidelines to incorporate cost-effectiveness in b/tsDMARD treatment.
Topics: Humans; Advisory Committees; Antirheumatic Agents; Arthritis, Rheumatoid; Cost-Benefit Analysis; Delphi Technique
PubMed: 36863753
DOI: 10.1136/rmdopen-2022-002898 -
Clinical and Experimental Rheumatology Sep 2023Ankylosing spondylitis (AS) is suspected to have increased risk of atherosclerosis and cardiovascular disease (CVD) mortality. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of individual serum lipids and analysis of lipid ratios in ankylosing spondylitis and healthy control cohorts: significantly lower mean HDL-cholesterol level in ankylosing spondylitis cohorts.
OBJECTIVES
Ankylosing spondylitis (AS) is suspected to have increased risk of atherosclerosis and cardiovascular disease (CVD) mortality. This systematic review and meta-analysis aims to critically study serum lipids and lipoprotein ratios in AS compared to healthy control (HC) subjects and determine any significant difference.
METHODS
English-language articles were systematically searched in PubMed, Ovid Medline, Embase (Medline records removed), and Scopus databases from 1970 to 2021. Random-effects model was used to pool results expressed as standardised mean difference (SMD) in the lipid outcomes. Lipid ratios of total ÷ HDL-C and the log10 (TG/HDL-C), i.e. atherogenic index of plasma (AIP), were analysed by histograms of differences in weighted means and weighted SDs between AS and HC exposure cohorts.
RESULTS
The meta-analysis included a total of 68 articles, 47 from database search and 21 from reference reviews. Pooled Hedges' g effect size revealed no difference in mean total cholesterol, mean triglycerides, and mean LDL-C between AS and HC subjects. However, mean HDL-C was significantly (p<0.001) lower in AS than HC subjects, with pooled Hedges' g (SE) for HDL-C of -0.484 (0.092), with 95% mean CIs [-0.664, -0.305]. In comparing differencesin AS minus HC weighted means of total HDL-C ratios, 8 values in HC were below the lowest ratio in AS.
CONCLUSIONS
Highly significantly lower HDL-C levels occurred in AS versus HC subjects. The lower HDL-C levels in AS than HC populations deserve further study and may be attributable to uninvestigated demographic, exercise capacity, or clinical manifestations.
Topics: Humans; Lipids; Spondylitis, Ankylosing; Triglycerides; Cholesterol, HDL; Cholesterol, LDL
PubMed: 36826790
DOI: 10.55563/clinexprheumatol/gtcard -
ARP Rheumatology 2023Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs),...
BACKGROUND
Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Healthcare professionals and patients in these populations should be alerted regarding the high risk of cardiovascular (CV) events and thus, customize the treatment strategy accordingly.
OBJECTIVE
This systematic literature review aimed to determine the effects of biological therapies on serious CV events in AS and PsA.
METHODS
Screening for the study was carried out using PubMed and Scopus databases from the database's inception to the 17th of July 2021. The literature search strategy for this review is based on the Population, Intervention, Comparator, Outcomes (PICOs) framework. Randomized controlled trials (RCTs) of biologic therapies for the treatment of AS and/or PsA were included. The primary outcome measure was the number of serious CV events reported during the placebo-controlled phase.
RESULTS
4,422 articles were generated from keywords, eligibility criteria, and databases. Following the screening, we retained 13 studies for analysis: 3 in AS and 10 in PsA. Meta-analysis of results was not feasible due to the small number of the identified studies, the heterogeneity of the biologic treatment and the included populations, as well as the infrequently reported requested endpoint. According to our review, biologic treatments are safe options as for CV risk in patients with PsA or AS.
CONCLUSION
Further and more extensive trials in AS/PsA patients at high risk of CV events are needed before firm conclusions can be drawn.
Topics: Humans; Arthritis, Psoriatic; Biological Products; Biological Therapy; Cardiovascular Diseases; Spondylitis, Ankylosing
PubMed: 36809367
DOI: No ID Found -
Mayo Clinic Proceedings Apr 2023
PubMed: 36792409
DOI: 10.1016/j.mayocp.2023.01.022 -
Zeitschrift Fur Rheumatologie Feb 2024This study aimed to update the prevalence estimates of inflammatory rheumatic diseases (IRD) in Germany.
OBJECTIVE
This study aimed to update the prevalence estimates of inflammatory rheumatic diseases (IRD) in Germany.
METHODS
A systematic literature search in PubMed and Web of Science (last search 08 November 2022) identified original articles (regional and nationwide surveys and claims data analyses for arthritides, connective tissue diseases, and vasculitides) on prevalences for the period 2014-2022. Data sources, collection period, case definition, and risk of bias are reported. Prevalences were estimated from available national data, with consideration of international data.
RESULTS
Screening by two authors yielded 263 hits, of which 18 claims data analyses and 2 surveys met the inclusion criteria. Prevalences ranged from 0.42 to 1.85% (rheumatoid arthritis), 0.32-0.5% (ankylosing spondylitis), 0.11-0.32% (psoriatic arthritis), 0.037-0.14% (systemic lupus erythematosus), 0.07-0.77% (Sjögren's disease/sicca syndrome), 0.14-0.15% (polymyalgia rheumatica, ≥ 40 years), 0.04-0.05% (giant cell arteritis, ≥ 50 years), and 0.015-0.026% (ANCA-associated vasculitis). The risk of bias was moderate in 13 and high in 7 studies. Based on the results, we estimate the prevalence of IRD in Germany to be 2.2-3.0%, which corresponds to approximately 1.5-2.1 million affected individuals. The prevalence of juvenile idiopathic arthritis was reported to be around 0.10% (0.07-0.10%) of 0-18-year-olds, corresponding to about 14,000 children and adolescents in Germany.
CONCLUSION
This systematic review shows an increase in the prevalence of IRD in Germany, which is almost exclusively based on claims data analyses. In the absence of multistage population studies, the available data are, overall, uncertain sources for prevalence estimates, with a moderate to high risk of bias.
Topics: Child; Adolescent; Humans; Prevalence; Arthritis, Rheumatoid; Spondylitis, Ankylosing; Polymyalgia Rheumatica; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Rheumatic Fever; Giant Cell Arteritis; Rheumatic Diseases
PubMed: 36749363
DOI: 10.1007/s00393-022-01302-5