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The Cochrane Database of Systematic... Jan 2023Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the... (Review)
Review
BACKGROUND
Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation.
OBJECTIVES
To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion.
DATA COLLECTION AND ANALYSIS
We applied standard Cochrane methodology.
MAIN RESULTS
We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. We assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.22 logMAR, 95% CI 0.13 to 0.31; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence). Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence). AUTHORS' CONCLUSIONS: Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time. To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.
Topics: Humans; Adrenal Cortex Hormones; Cataract; Glaucoma; Panuveitis; Quality of Life; Steroids; Uveitis; Uveitis, Intermediate; Randomized Controlled Trials as Topic
PubMed: 36645716
DOI: 10.1002/14651858.CD010469.pub3 -
Ocular Immunology and Inflammation Jan 2024To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To examine the long-term efficacy and safety of adalimumab (ADA) in patients with Behçet uveitis (BU).
METHODS
A systematic review and meta-analysis of observational studies was performed. Pooled results are presented as mean difference or standardized mean difference (std diff) and 95% confidence intervals (CI). Visual acuity (VA), intraocular inflammation grade, central macular thickness, corticosteroid (CS) sparing effect and adverse events were evaluated.
RESULTS
Ten studies were included finally for quantitative and qualitative synthesis. ADA therapy resulted in 0.124 (95%CI: 0.084, 0.165) logMAR improvement in VA. In addition, ADA therapy resulted in decreased grade of intraocular inflammation [std diff, -1.187 (95%CI: -1.508, -0.866)] and macular thickness [std diff, -0.564 (95%CI: -0.843, -0.286)] and caused a decrease in CS dosage [std diff, -1.809 (95%CI: -2.420, -1.198)]. The pooled rate of overall adverse events for ADA in 301 patients was 8.5% (95%CI: 0.039, 0.177).
CONCLUSION
ADA is an efficient therapy that improves VA and controls intraocular inflammation, macular edema and retinal vasculitis. As the disease exposure time increased, improvement in VA was less. The safety and CS-sparing effect of ADA were demonstrated with few adverse effects. The results provided evidence that ADA can be used safely and efficiently as the first-line drug in patients with BU.
Topics: Humans; Adalimumab; Uveitis; Behcet Syndrome; Inflammation; Retinal Vasculitis
PubMed: 36625549
DOI: 10.1080/09273948.2022.2157288 -
Current Opinion in Rheumatology Jan 2023Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent...
PURPOSE OF THE REVIEW
Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent advances in the role of Treg and interleukin (IL)-10 in the pathogenesis and treatment of systemic vasculitis, including giant cell arteritis (GCA), Takayasu arteritis, Behçet's disease, antineutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV), and cryoglobulinemia associated vasculitis.
RECENT FINDINGS
Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Decreased peripheral blood frequencies of Treg are described in all vasculitis when compared to healthy donors. Altered Treg functions are reported in GCA, Takayasu arteritis, AAV, and Behçet's disease with different mechanisms proposed. Treatment with biologics, and sometimes other immunosuppressants, may restore Treg frequencies and/or immune activity with significant differences in active disease or disease in remission in several systemic vasculitis. IL-10 is elevated in GCA, AAV, cryoglobulinemia associated vasculitis. In Behçet's disease, IL-10 is decreased in peripheral blood and elevated in saliva. In Takayasu arteritis, IL-10 levels were essentially elevated in patients' vessel wall. Several new therapeutic approaches targeting Treg and Il-10 (low dose IL-2, CAR Treg…) are developed to treat patients with systemic vasculitis.
SUMMARY
Treg and IL-10 play a central role in the regulation of inflammation in vasculitis and new targeting approaches are emerging.
Topics: Humans; T-Lymphocytes, Regulatory; Interleukin-10; Behcet Syndrome; Giant Cell Arteritis; Takayasu Arteritis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 36508306
DOI: 10.1097/BOR.0000000000000915 -
The Cochrane Database of Systematic... Oct 2022Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU.
OBJECTIVES
To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group.
AUTHORS' CONCLUSIONS
There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.
Topics: Adult; Humans; Macular Edema; Cyclosporine; Mycophenolic Acid; Tacrolimus; Azathioprine; Methotrexate; Steroids; Immunosuppressive Agents; Panuveitis; Inflammation; Antirheumatic Agents
PubMed: 36315029
DOI: 10.1002/14651858.CD014831.pub2 -
Ophthalmic Epidemiology Oct 2023Clinical trials in uveitis have led to the expansion of therapeutic options for the management of non-infectious uveitis. The purpose of this systematic review is to... (Review)
Review
PURPOSE
Clinical trials in uveitis have led to the expansion of therapeutic options for the management of non-infectious uveitis. The purpose of this systematic review is to investigate why some clinical trials have yielded successful results and regulatory approval of new therapies, and some have not.
METHODS
A systematic literature search of the Pubmed/MEDLINE database and clinicaltrials.gov was performed from 2006 to 2021, according to the PRISMA guidelines. Phase III clinical trials of systemic and local therapies in adults with non-infectious intermediate, posterior, and panuveitis were included.
RESULTS
A total of 79 clinical trials were collected from ClinicalTrials.gov and PubMed/MEDLINE database search. Based on the inclusion and exclusion criteria, 14 clinical trials were included.
CONCLUSION
This review summarizes the study design, outcome measures, and results of recent phase III trials in non-infectious uveitis, in the interest of understanding limitations and rethinking new methods of defining endpoints in clinical trial design.
Topics: Adult; Humans; Uveitis; Panuveitis; Outcome Assessment, Health Care; Visual Acuity
PubMed: 36204817
DOI: 10.1080/09286586.2022.2131837 -
Rheumatology International Jan 2023Behçet's Disease (BD) can be correlated with sleep impairment and fatigue, resulting in low quality of life (QoL); however, a comprehensive evaluation of this issue is... (Review)
Review
Behçet's Disease (BD) can be correlated with sleep impairment and fatigue, resulting in low quality of life (QoL); however, a comprehensive evaluation of this issue is still missing. We performed a systematic literature review (SLR) of existing evidence in literature regarding sleep quality in BD. Fifteen papers were included in the SLR. Two domains were mainly considered: global sleep characteristics (i) and the identification of specific sleep disorders (ii) in BD patients. From our analysis, it was found that patients affected by BD scored significantly higher Pittsburgh Sleep Quality Index (PSQI) compared to controls. Four papers out of 15 (27%) studied the relationship between sleep disturbance in BD and disease activity and with regards to disease activity measures, BD-Current Activity Form was adopted in all papers, followed by Behçet's Disease Severity (BDS) score, genital ulcer severity score and oral ulcer severity score. Poor sleep quality showed a positive correlation with active disease in 3 out of 4 studies. Six papers reported significant differences between BD patients with and without sleep disturbances regarding specific disease manifestations. Notably, arthritis and genital ulcers were found to be more severe when the PSQI score increased. Our work demonstrated lower quality of sleep in BD patients when compared to the general population, both as altered sleep parameters and higher incidence of specific sleep disorders. A global clinical patient evaluation should thereby include sleep assessment through the creation and adoption of disease-specific and accessible tests.
Topics: Humans; Behcet Syndrome; Quality of Life; Sleep Quality; Sleep; Sleep Wake Disorders
PubMed: 36194239
DOI: 10.1007/s00296-022-05218-w -
Ocular Immunology and Inflammation Nov 2023Choroidal neovascularization (CNV) affects 64-75% of eyes with punctate inner choroidopathy (PIC). Although anti-VEGF agents are considered first-line therapy, there is...
Choroidal neovascularization (CNV) affects 64-75% of eyes with punctate inner choroidopathy (PIC). Although anti-VEGF agents are considered first-line therapy, there is controversy regarding other modalities, such as immunosuppression. We performed a systematic review of individual participant data (IPD) and generated a dataset of 278 eyes with PIC-related CNV from 45 studies. Forty-two percent presented with moderate visual loss (MVL) or worse. Four different treatment modalities (anti-VEGF, photodynamic therapy, local immunosuppression, and systemic immunosuppression) and most combinations among them were represented. Anti-VEGF injections decreased the likelihood of MVL (Odds Ratio 0.3, p = .027), an effect moderated by presenting visual acuity and patient age. Eyes receiving more than 3 injections were more likely to receive additional therapeutic modalities. Increasing number of modalities was associated with longer follow-up time and did not improve vision. The beneficial effect of anti-VEGF injections persisted when controlling for presenting visual acuity and follow-up time.
Topics: Humans; Choroidal Neovascularization; White Dot Syndromes; Eye; Fluorescein Angiography; Angiogenesis Inhibitors; Retrospective Studies
PubMed: 36179037
DOI: 10.1080/09273948.2022.2124176 -
Clinical and Experimental Rheumatology Sep 2022The assessment of quality of life (QoL) in Behçet's disease (BD) patients has been a surrogate of disease outcomes, but a wider impact on the patient's lifestyle has... (Review)
Review
OBJECTIVES
The assessment of quality of life (QoL) in Behçet's disease (BD) patients has been a surrogate of disease outcomes, but a wider impact on the patient's lifestyle has not been considered. This systematic review aims to provide an overview of the existing tools specifically adopted to explore the QoL in BD patients.
METHODS
A systematic literature review was conducted using 2 electronic databases, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A combination of BD and QoL-related search terms were used. All articles were screened by 3 independent reviewers for title, abstract and full text level. Studies investigating QoL in BD patients were included.
RESULTS
64 papers of 497 records were retained. Data about 7,449 patients with a BD diagnosis and QoL evaluation were collected. 47 different tools to evaluate QoL were detected. The mean number of tools adopted in each study was 2.14±1.34. General QoL and psychological and social impact were investigated in 68.75% and 54.69% respectively. The correlation with disease activity was investigated in 71.86%.
CONCLUSIONS
The assessment of QoL in BD patients may provide a fundamental measurement for health to evaluate the outcome of interventions for BD patients. The adoption of a single validated QoL tool, developed including the BD patient's perspective, may provide an accurate and effective assessment, ensure the comparison within different cohorts, and set standardised values to define QoL level in BD patients.
Topics: Behcet Syndrome; Humans; Quality of Life
PubMed: 36106544
DOI: 10.55563/clinexprheumatol/sian1b -
Clinical and Experimental Rheumatology Sep 2022Behçet's syndrome (BS) has been reported with cardiovascular involvement. It's still unclear that BS is associated with the increased risk of ischaemic heart disease... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Behçet's syndrome (BS) has been reported with cardiovascular involvement. It's still unclear that BS is associated with the increased risk of ischaemic heart disease (IHD). We aimed to conduct a meta-analysis concerning the incidence of IHD in BS and identify the relationship between IHD and BS.
METHODS
We performed a comprehensive literature search based on PubMed and Embase databases up to 7 July, 2021. Incidence of IHD was calculated by metaproportion. Pooled risk ratio and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird.
RESULTS
Four studies with 9237 patients with IHD in BS and 40353 controls were identified and included in our meta-analysis. The pooled risk ratio of IHD in patients with BS was 1.30 and achieved statistical significance (95% CI 1.04-1.64). The statistical heterogeneity was low with an I2 of 39% (p=0.18).
CONCLUSIONS
In this meta-analysis the presence of BS was associated with an increased risk of IHD. Prospective researches should be done to determine the pathophysiological and prognostic implications of increased IHD in BS.
Topics: Behcet Syndrome; Coronary Artery Disease; Humans; Incidence; Myocardial Ischemia; Prospective Studies; Risk Factors
PubMed: 35699061
DOI: 10.55563/clinexprheumatol/1shqmz -
Disease Markers 2022Methylenetetrahydrofolate reductase (MTHFR) is a critical rate-limiting enzyme in the homocysteine/methionine metabolism pathway that is implicated in the pathogenesis... (Meta-Analysis)
Meta-Analysis
Methylenetetrahydrofolate reductase (MTHFR) is a critical rate-limiting enzyme in the homocysteine/methionine metabolism pathway that is implicated in the pathogenesis and progression of autoimmune diseases. Previous association studies have been performed to investigate the effect of polymorphisms in on the risk of autoimmune diseases with inconsistent results. Therefore, this meta-analysis was designed to assess the association between the 677 C/T and 1298 A/C polymorphisms and the susceptibility to autoimmune diseases. We identified reports by a literature search in the following electronic databases: PubMed, Ovid, Web of science, and China National Knowledge Infrastructure. Statistical analyses of the summary odds ratios (ORs) and 95% confidence intervals (CIs) were done using STATA software. In a recessive genetic model, the 677 C/T polymorphism was associated with an increased risk of Behcet's disease (OR = 1.97, 95% CI, 1.31-2.97), multiple sclerosis (OR = 1.57, 95% CI, 1.03-2.38), and ankylosing spondylitis (OR = 2.90, 95% CI, 1.92-4.38). The 1298 A/C polymorphism was associated an increased risk of multiple sclerosis in a heterozygote comparison (OR = 2.36, 95% CI, 1.29-4.30) and in a dominant model (OR = 2.31, 95% CI, 1.24-4.29). This meta-analysis demonstrated that the 677 C/T was a risk factor for Behcet's disease, multiple sclerosis, and ankylosing spondylitis, and the 1298 A/C was a risk factor for multiple sclerosis.
Topics: Autoimmune Diseases; Behcet Syndrome; Genetic Predisposition to Disease; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Multiple Sclerosis; Polymorphism, Genetic; Spondylitis, Ankylosing
PubMed: 35686035
DOI: 10.1155/2022/4568145