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Frontiers in Immunology 2023Traditional Chinese medicines (TCMs), such as Tripterygium wilfordii Hook F (TwHF), Glycyrrhiza uralensis, Caulis sinomenii and others have anti-inflammatory effects.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditional Chinese medicines (TCMs), such as Tripterygium wilfordii Hook F (TwHF), Glycyrrhiza uralensis, Caulis sinomenii and others have anti-inflammatory effects. They are widely used in China to treat rheumatoid arthritis (RA), but proof of their use as an evidence-based medicine is little. The aim of this network meta-analysis (NMA) was to evaluate the efficacy and safety of TCMs.
METHODS
By searching online databases and using a manual retrieval method, randomized controlled trials (RCTs) that met specific selection criteria were included in the meta-analysis. The search included papers that were published between the establishment of the databases and November 10, 2022. Analyses were performed using Stata software (version 14) and Review Manager (version 5.3).
RESULTS
61 papers with 6316 subjects were included in the current NMA. For ACR20, MTX plus SIN therapy (94.30%) may be a significant choice. For ACR50 and ACR70, MTX plus IGU therapy (95.10%, 75.90% respectively) performed better than other therapies. IGU plus SIN therapy (94.80%) may be the most promising way to reduce DAS-28, followed by MTX plus IGU therapy (92.80%) and TwHF plus IGU therapy (83.80%). In the analysis of the incidence of adverse events, MTX plus XF therapy (92.50%) had the least potential, while LEF therapy (22.10%) may cause more adverse events. At the same time, TwHF therapy, KX therapy, XF therapy and ZQFTN therapy were not inferior to MTX therapy.
CONCLUSIONS
TCMs with anti-inflammatory effect were not inferior to MTX therapy in the treatment of RA patients. Combining with TCMs can improve the clinic efficacy and reduce the possibility of adverse events of DMARDs, which may be a promising regimen.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022313569.
Topics: Humans; Methotrexate; Network Meta-Analysis; Arthritis, Rheumatoid; Antirheumatic Agents; Tripterygium; Anti-Inflammatory Agents
PubMed: 36969172
DOI: 10.3389/fimmu.2023.1114930 -
Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
Clinical and Experimental Rheumatology Sep 2023Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a co-stimulatory signal necessary for T cell activation. We aimed to analyse the efficacy and safety of abatacept in the management of rheumatoid arthritis using the Cochrane systematic review.
METHODS
We conducted a systematic search among PubMed, Cochrane central register of controlled trials, Web of Science, and Embase databases from the establishment of these databases to April 2022. The effectiveness and safety of abatacept in treating rheumatoid arthritis were assessed in terms of American College of Rheumatology (ACR) 20/50/70/90 responses, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS-28-CRP), and adverse events. The Relative Risks (RRs) of relative safety and efficacy and their corresponding 95 confidence intervals (CIs) were used to compute the pooled assessments of the outcomes. We used the review manager software version 5.4 to analyse our data, and the PRISMA checklist 2020 was used to ensure that our work conforms with the specification of meta-analysis.
RESULTS
Our study included 13 randomised control trials with a total of 5978 adult patients from different geographic regions and races. Following the combined analysis of these enrolled studies, the RRs for ACR 20/50/70/90 responses were 1.57 [95%CI 1.27, 1.93], 1.84 [95%CI 1.38, 2.44], 2.36 [95%CI 1.60, 3.47], and 2.95 [95%CI 1.88, 4.63], respectively. Such findings suggest that abatacept-treated patients were 1.57, 1.84, 2.36, and 2.95 times more likely to achieve ACR 20/50/70/90 responses, respectively, than those treated with placebo, conventional synthetic disease-modifying antirheumatic drugs, and or other biologic disease-modifying anti-rheumatic drugs. An exclusive comparison of abatacept and other biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) indicated that participants who were treated with abatacept could achieve better ACR responses than those treated with other b/tsDMARDs. Adverse events were less seen in abatacept-treated patients than in those who were given other b/tsDMARDs.
CONCLUSIONS
This meta-analysis concludes that in adult with rheumatoid arthritis, abatacept can achieve better health outcomes than other biologic drugs.
Topics: Adult; Humans; Abatacept; Methotrexate; Arthritis, Rheumatoid; Antirheumatic Agents; Biological Products; Randomized Controlled Trials as Topic
PubMed: 36912326
DOI: 10.55563/clinexprheumatol/2xjg0d -
Journal of Clinical Rheumatology :... Jun 2023We aimed to demonstrate that the proportion of rheumatoid arthritis patients achieving 20%/50%/70% improvement in American College of Rheumatology (ACR20/50/70)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We aimed to demonstrate that the proportion of rheumatoid arthritis patients achieving 20%/50%/70% improvement in American College of Rheumatology (ACR20/50/70) responses to Food and Drug Administration-approved biologic disease-modifying antirheumatic drugs (bDMARDs) after an inadequate response to methotrexate (MTX) and after failure of the first bDMARDs followed a consistent pattern.
METHODS
This systematic review and meta-analysis was performed in accordance with MECIR (Methodological Expectations for Cochrane Intervention Reviews) standards. Two separate groups of randomized controlled trials were included: the first group included studies with biologic-naive patients who added bDMARD to MTX as intervention arm compared with the placebo plus MTX group. The second group included biologic-irresponsive (IR) patients who used a second bDMARD plus MTX after the first bDMARD failure compared with placebo plus MTX group. Primary outcome was defined as the proportion of rheumatoid arthritis patients achieving ACR20/50/70 responses at 24 ± 6 weeks.
RESULTS
Twenty-one studies initiated between 1999 and 2017 were included: 15 studies for the biologic-naive group and 6 studies for the biologic-IR group. For the biologic-naive group, the proportions of patients achieving ACR20/50/70 were 61.4% (95% confidence interval [CI], 58.7%-64.1%), 37.8% (95% CI, 34.8%-40.8%), and 18.8% (95% CI, 16.1%-21.4%), respectively. For the biologic-IR group, proportions of patients achieving ACR20/50/70 were 48.5% (95% CI, 42.2%-54.8%), 27.3% (95% CI, 21.6%-33.0%), and 12.9% (95% CI, 11.3%-14.8%), respectively.
CONCLUSION
We were able to systematically demonstrate that ACR20/50/70 responses to biologic-naive follow a consistent pattern of 60%, 40%, and 20%, respectively. We also demonstrated that the ACR20/50/70 responses to a biologic IR follow a certain pattern of 50%, 25%, and 12.5%, respectively.
Topics: Humans; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Pyrroles; Drug Therapy, Combination; Biological Products; Treatment Outcome
PubMed: 36870081
DOI: 10.1097/RHU.0000000000001945 -
Current Rheumatology Reviews Jun 2023Necrotizing scleritis (NS) presents 30%-40% as having a systemic autoimmune condition.
INTRODUCTION
Necrotizing scleritis (NS) presents 30%-40% as having a systemic autoimmune condition.
OBJECTIVE
To present a clinical case report and a systematic review of necrotizing scleritis with ocular manifestation as the first sign of rheumatologic disease.
METHODS
The present study was elaborated according to the rules of CARE.
CASE REPORT
A female patient, 63 years old, a white, administrative assistant, presented irritation, low visual acuity (LVA) in the left eye (LE), and headache. Biomicroscopy (BIO) in the right eye (RE) was normal, and the LE showed hyperemia and scleral thinning. After 1 month, the patient returns without signs of infectious diseases in the exams, and after a rheumatological evaluation with a diagnosis of rheumatoid arthritis, methotrexate and prednisone are prescribed. After 2 months, she relapsed and started treatment with anti-TNF, with remission after the 4th dose. After 1 year, she evolved with LVA in LE.
RESULTS
A total of 244 articles were found, 104 articles were evaluated and 10 were included in the brief review. The symmetrical Funnel Plot does not suggest a risk of bias.
CONCLUSION
Both in the present case report and the literary findings, it was evidenced that the ophthalmologic findings may precede the systemic changes of the disease for the early diagnosis of rheumatoid arthritis.
Topics: Humans; Female; Middle Aged; Scleritis; Tumor Necrosis Factor Inhibitors; Arthritis, Rheumatoid; Inflammation; Methotrexate
PubMed: 36809968
DOI: 10.2174/1573397119666230222093007 -
Clinical Rheumatology Jun 2023Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with... (Meta-Analysis)
Meta-Analysis Review
Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022358082. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58], P = 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87], P = 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79], P = 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48], P = 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: - 0.28 with 95% CI [- 0.38, - 0.18], P = 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs. Key Points • OKZ is effective especially with methotrexate in RA patients.
Topics: Humans; Methotrexate; Network Meta-Analysis; Arthritis, Rheumatoid; Antirheumatic Agents; Treatment Outcome
PubMed: 36792848
DOI: 10.1007/s10067-023-06519-6 -
Journal of Osteopathic Medicine Apr 2023Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood.
OBJECTIVES
The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework.
METHODS
On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity.
RESULTS
A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002).
CONCLUSIONS
Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.
Topics: Humans; Adult; Middle Aged; Glucocorticoids; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Pneumonia
PubMed: 36691851
DOI: 10.1515/jom-2022-0177 -
Modern Rheumatology Dec 2023In the current study, we aimed to investigate the effect of smoking on inadequate response to methotrexate (MTX-IR) in rheumatoid arthritis (RA) patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
In the current study, we aimed to investigate the effect of smoking on inadequate response to methotrexate (MTX-IR) in rheumatoid arthritis (RA) patients.
METHODS
We searched PubMed, Embase, and Web of Science until 6 June 2022. Observational or interventional studies investigating MTX-IR in RA patients based on smoking status were included. Two independent reviewers assessed the risk of bias and the certainty of the evidence using the Risk of Bias in Nonrandomized Studies-of Interventions and Grades of Recommendation, Assessment, Development, and Evaluation tools, respectively.
RESULTS
We included 23 studies in the systematic review and 13 in the meta-analysis. Of the 13 included studies, 6 had a moderate risk, 3 had a serious risk, and 4 had a critical risk of bias. The overall random-effect meta-analysis suggested that smokers were 58% more likely to be MTX-IR when compared with nonsmokers [odds ratio (OR) 1.58, 95% confidence interval 1.21-2.06; P = .001; I2 = 69.3%]. The common-effect meta-analysis of the adjusted ORs demonstrated an overall OR of 2.69 (1.88-3.83; P < .001; I2 = 27.1%).
CONCLUSIONS
The current study showed that smoking is a significant predictor of MTX-IR, especially in disease-modifying antirheumatic drug-naïve early RA patients, as most of the included studies in the meta-analysis consisted of this population.
Topics: Humans; Methotrexate; Smoking; Arthritis, Rheumatoid; Antirheumatic Agents; Drug Therapy, Combination
PubMed: 36688574
DOI: 10.1093/mr/road013 -
BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
Seminars in Arthritis and Rheumatism Apr 2023The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA).
METHODS
We systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method.
RESULTS
The literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence. In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64-0.84), angiographic stabilization was observed in 86% (0.77-0.94) and relapses in 12% (0.05-0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28-21.16). Adverse events were observed in 8% of patients (0.02-0.16). Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy. In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17-0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29-32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 - 0.80). Relapses were observed in 21% of cases (0.14- 0.28) and adverse events in 28% (0.12-0.46). Comparison of LEF with MTX showed similar efficacy and tolerance.
CONCLUSION
LEF is well tolerated and might be effective for patients with TAK and GCA.
Topics: Humans; Leflunomide; Antirheumatic Agents; Methotrexate; Giant Cell Arteritis; Takayasu Arteritis; Glucocorticoids; Cohort Studies; Recurrence
PubMed: 36645992
DOI: 10.1016/j.semarthrit.2023.152166