-
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 -
Rheumatology (Oxford, England) Mar 2015The aim of this study was to examine the link between AS and periodontitis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to examine the link between AS and periodontitis.
METHODS
Medline, Embase, AMED, CINAHL, Web of Science and Google Scholar were searched to identify eligible studies that were selected and reviewed independently by at least two authors.
RESULTS
Six case-control studies were included in the review. Study size ranged from 90 to 40 926 participants. The prevalence of periodontitis ranged from 38% to 88% in AS patients and from 26% to 71% in controls. As there was low-level heterogeneity (I(2) = 13%), using fixed effects analysis the overall pooled estimate of the odds ratios for periodontitis was 1.85 (95% CI 1.72, 1.98). There was no evidence of publication bias.
CONCLUSION
The results led to the need for a further large study with sufficient statistical power to detect the desired effect size, taking into account potential confounding factors and using validated measures of AS and periodontitis.
Topics: Case-Control Studies; Humans; Periodontitis; Prevalence; Risk Factors; Spondylitis, Ankylosing
PubMed: 25213130
DOI: 10.1093/rheumatology/keu356 -
European Journal of Rheumatology Jul 2021A close association between periodontal disease (PD) and ankylosing spondylitis (AS) has long been speculated. Both diseases are characterized by dysregulation of the...
A close association between periodontal disease (PD) and ankylosing spondylitis (AS) has long been speculated. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of the soft and hard connective tissue. There is evidence of increased levels of tumor necrosis factor-alpha and various interleukins in both patients of AS and periodontitis. This study aimed to conduct a systematic review exploring the relationship between AS and PD. We searched MEDLINE - Embase databases (from their inception till October 2019) using appropriate combinations of the following search items with limits '(English, Human)': Ankylosing spondylitis, spondyloarthritis, spondyloarthropathies, spondyloarthritides, spinal disease, musculoskeletal disease, rheumatic disease and periodontitis, PD, periodontoses, parodontoses, chronic periodontitis, gum disease, gingivitis, oral health, dental health, plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL). This search was supplemented by the manual search of bibliographies of the selected articles and conference proceedings of the European League against Rheumatism. Only the reviews and observational studies of cross-sectional, cohort, or case-control type on adult patients with AS were selected. Data were extracted from a predesigned PROforma. A total of 984 articles were identified, and 12 were selected for a detailed appraisal. All the identified studies were of the case-control type. The prevalence of periodontitis ranged from 38% to 88% in patients with AS and 26% to 71% in the control group. Of the 12 studies, 2 showed significant changes in PI, 2 showed altered PPD, 3 showed significantly increased CAL, and 2 showed increased BOP. In 7 studies, periodontitis was seen in a significant number of patients with AS (p<0.05). All the studies reported that the prevalence of PD in patients with AS was higher than that in patients without AS. Our systematic review found an association between AS and PD. Patients with AS show a higher prevalence of periodontitis and poor oral hygiene than the healthy controls.
PubMed: 33284102
DOI: 10.5152/eurjrheum.2020.20177 -
Annals of Palliative Medicine May 2020To systematically evaluate the efficacy of moxibustion in the treatment of ankylosing spondylitis (AS). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the efficacy of moxibustion in the treatment of ankylosing spondylitis (AS).
METHODS
Seven electronic databases were systematically searched for relevant studies for inclusion from databases inception to December 31, 2018. Randomized controlled trials investigating the efficacy of moxibustion for AS treatment versus Western medicine (Wm) treatment were included for systematic review and meta-analysis. Effect estimates were pooled using the fixed or random-effects models. Between-study heterogeneity and publication bias were also assessed. Stratification analyses were further performed based on the treatment plan of experimental groups.
RESULTS
Twenty-six studies were eligible for inclusion with a total of 1,944 AS patients. Meta-analysis showed that compared with those receiving Wm treatment alone, patients receiving moxibustion combined with Wm treatment or moxibustion alone had a higher clinical efficacy rate [odds ratio (OR) =4.21, 95% confidence interval (CI): 2.91 to 6.10, P<0.001 for moxibustion combined with Wm versus Wm; OR =2.43, 95% CI: 1.62 to 3.65, P<0.001 for moxibustion alone versus Wm]. In addition, patients receiving moxibustion combined with Wm treatment had lower levels of C-reactive protein [weighed-median difference (WMD) =-6.33, 95% CI: -9.64 to -3.01, P<0.001] and erythrocyte sedimentation rate (WMD =-7.86, 95% CI: -11.26 to -4.46, P<0.001) after treatment, respectively. Furthermore, moxibustion could also improve Schober test scores (WMD =0.85, 95% CI: 0.15 to 1.55, P=0.017), occipital-wall distances (WMD =-0.55, 95% CI: -0.92 to -0.19, P=0.003), and finger-ground distances (WMD =-3.64, 95% CI: -5.61 to -1.68, P<0.001) of AS patients.
CONCLUSIONS
This study suggests that moxibustion is an effective complementary treatment for AS patients. However, further large-scale multicenter clinical trials are needed to confirm these findings.
Topics: Humans; Moxibustion; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 32312058
DOI: 10.21037/apm.2020.02.31 -
BioDrugs : Clinical Immunotherapeutics,... Aug 2017A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.
METHODS
Literature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn's disease, and ulcerative colitis.
RESULTS
Of >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0-83%), adalimumab (0-54%), and infliximab biosimilar CT-P13 (21-52%), and the lowest with secukinumab (0-1%), ustekinumab (1-11%), etanercept (0-13%), and golimumab (0-19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb- patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.
CONCLUSIONS
Based on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.
Topics: Abatacept; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Juvenile; Arthritis, Psoriatic; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Colitis, Ulcerative; Crohn Disease; Etanercept; Humans; Infliximab; Spondylitis, Ankylosing; Ustekinumab
PubMed: 28612180
DOI: 10.1007/s40259-017-0231-8 -
Lung India : Official Organ of Indian... 2016Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk...
BACKGROUND
Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk of venous thromboembolism (VTE). However, the data on ankylosing spondylitis (AS) are limited.
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 the risk of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS participants. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.
RESULTS
Of 423 potentially relevant articles, three studies met our inclusion criteria and thus, were included in the data analysis. The pooled risk ratio of VTE in patients with AS was 1.60 (95% confidence interval: 1.05-2.44). The statistical heterogeneity of this study was high with an I of 93%.
CONCLUSION
Our study demonstrated a statistically significant increased VTE risk among patients with AS.
PubMed: 27890993
DOI: 10.4103/0970-2113.192862 -
Archives of Medical Research Feb 2016Leptin is an adipokine that has several effects on metabolism and immune system in patients with ankylosing spondylitis (AS). The present investigations of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Leptin is an adipokine that has several effects on metabolism and immune system in patients with ankylosing spondylitis (AS). The present investigations of the relationship between plasma/serum leptin levels and AS are contradictory. To derive a more precise estimation on the plasma/serum leptin levels in AS patients and related factors, a meta-analysis was performed.
METHODS
Published literature that compares plasma/serum leptin levels between AS group and control group from PubMed, Embase, Cochrane Library and other databases were searched. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analyses. Statistical heterogeneity within studies was examined by the Q statistic.
RESULTS
A total of eight studies including 391 AS patients and 293 healthy controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between AS patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.384, 95% CI = -1.522 to 0.753). Meanwhile, subgroup analyses by gender also showed no significant differences in plasma/serum leptin levels between case group and controls.
CONCLUSION
There is no significant difference in plasma/serum leptin levels between AS patients and controls.
Topics: Adipokines; Case-Control Studies; Humans; Leptin; Plasma; Serum; Spondylitis, Ankylosing
PubMed: 27016486
DOI: 10.1016/j.arcmed.2016.03.001 -
Psychiatry Investigation Aug 2019The aim of this study was to provide a summary estimate of depression prevalence among people with ankylosing spondylitis (AS) in comparison to those without AS. A...
The aim of this study was to provide a summary estimate of depression prevalence among people with ankylosing spondylitis (AS) in comparison to those without AS. A systematic literature search was conducted using PubMed, Embase, PsycINFO, Web of Science, the Cochrane database library, China National Knowledge Infrastructure, and Wanfang Database from their inception to December 2016. The results showed that thirty-one eligible studies involving 8,106 patients were analyzed. Fifteen methods of defining depression were reported. The overall pooled prevalence of depression was 35% (95% CI, 28-43%), with high between-study heterogeneity (I2=98.8%, p<0.001). The relative risk of depression among people with AS was 1.76 (95% CI: 1.21-2.55, eight studies, n=3,006) compared with people without AS. The depression score [standardized mean difference (SMD)=0.43, 95% CI: 0.19-0.67, seven studies, n=549] was higher in AS patients than in controls. The main influence on depression prevalence was the sample size and country of origin. In conclusion, one-third of people with AS experience symptoms of depression. Depression was more prevalent in AS patients than in controls. Further research is needed to identify effective strategies for preventing and treating depression among AS patients.
PubMed: 31446684
DOI: 10.30773/pi.2019.06.05 -
Postgraduate Medical Journal Sep 2018The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF THE STUDY
The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta (IL-12B), IL-10 and tumour necrosis factor (TNF)-α polymorphisms with ankylosing spondylitis (AS) susceptibility.
STUDY DESIGN
A systematic literature search was conducted to identify the relevant studies. Pooled OR with 95% CI was calculated to assess the strength of the association in a fixed or random-effects model.
RESULTS
A total of 13 917 cases and 19 849 controls in 43 eligible studies were included in the meta-analysis. Seventeen single-nucleotide polymorphisms (SNPs) in the abovementioned five cytokine genes were evaluated. The results indicate that the nine SNPs (rs11209026, rs1004819, rs10489629, rs11465804, rs1343151, rs11209032, rs1495965, rs7517847, rs2201841) of IL-23R are associated with AS susceptibility in all study subjects in the allelic model. Moreover, stratification by ethnicity identified a significant association between seven SNPs of IL-23R and AS susceptibility in Europeans and Americans, but not in Asians. In addition, the IL-10-819 C/T and TNF-α-857 C/T polymorphisms also confer susceptibility to AS, especially in Asian population.
CONCLUSION
The results suggested that the genetic susceptibility for AS is associated with the nine SNPs of IL-23R in overall population. In the subgroup analysis, significant associations were shown in European and American population, but not in Asian population. Our results also suggest that IL-10-819 C/T and TNF-α-857 C/T polymorphism might be associated with AS risk, especially in Asian population.
Topics: Cytokines; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Spondylitis, Ankylosing
PubMed: 30322951
DOI: 10.1136/postgradmedj-2018-135665 -
Annals of the Rheumatic Diseases Jan 2021Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the...
OBJECTIVES
Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety.
METHODS
Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.
RESULTS
The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.
CONCLUSION
The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.
Topics: Adamantane; Advisory Committees; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azetidines; Cytokines; Drug Therapy, Combination; Europe; Heterocyclic Compounds, 3-Ring; Humans; Inflammatory Bowel Diseases; Janus Kinase Inhibitors; Niacinamide; Piperidines; Psoriasis; Purines; Pyrazoles; Pyridines; Pyrimidines; Rheumatology; Spondylarthropathies; Spondylitis, Ankylosing; Sulfonamides; Triazoles
PubMed: 33158881
DOI: 10.1136/annrheumdis-2020-218398