Influence of RFC1 c.80A>G Polymorphism on Methotrexate-Mediated Toxicity and Therapeutic Efficacy in Rheumatoid Arthritis: A Meta-analysis

2021 ◽  
pp. 106002802110020
Author(s):  
Shaik Mohammad Naushad ◽  
Salman A. Alrokayan ◽  
Fahad N. Almajhdi ◽  
Tajamul Hussain
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Efficacy ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Random Effect ◽  
Reduced Folate Carrier ◽  
Gene Variant ◽  
Efficacy And Safety ◽  
Random Effect Models ◽  
Reduced Risk

Background: Methotrexate (MTX) is an antirheumatic drug, transported by reduced folate carrier-1 (RFC1). The most common RFC1 gene variant, c.80 A>G (rs1051266) is ambiguously linked to adverse effects of MTX therapy in some rheumatoid arthritis (RA) patients. Objective: The purpose of meta-analysis was to summarize all major published studies on c.80 A>G SNP to clarify this ambiguity in MTX therapy. Methods: A total of 18 studies representing 3592 RA patients comprising 699 men and 2893 women were included. Both fixed and random effect models were applied to study the data. Results: The RFC1 80A-allele showed null association with MTX-mediated toxicity in both fixed (odds ratio [OR] = 0.91; 95% CI = 0.80-1.03) and random effects (OR = 0.89; 95% CI: 0.71-1.11) models. Because heterogeneity was observed in this association ( P = 0.0006), data were segregated based on use of folate therapy. In 7 studies (n = 1191) where folate was used along with MTX, RFC1 AA patients showed reduced risk for MTX-mediated toxicity (OR = 0.67; 95% CI: 0.50-0.89; P = 0.0006). The RFC1 80A-allele was found to increase the efficacy of MTX therapy by 1.53-fold (95% CI: 1.24-1.88), whereas the 80AA-genotype increased the efficacy by 1.85-fold (95% CI: 1.41-2.42). No publication bias was observed in these associations. Conclusion and Relevance: RFC1 c.80 A>G is an important pharmacogenetic determinant of MTX therapy in RA. The RFC1 80A-allele robustly increased therapeutic efficacy and safety when folate was used along with MTX. Findings are relevant to decision-making in the clinical use of MTX as a treatment for RA patients harboring the RFC1 gene variant.

scholarly journals PENGARUH KONSUMSI SERAT DENGAN PENGURANGAN RISIKO KANKER KOLON DI NEGARA BARAT: STUDI META ANALISIS

2018 ◽  
Vol 12 (2) ◽  
pp. 97
Author(s):  
Masrul Masrul
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Western Countries ◽  
Colorectal Cancer Patients ◽  
Published Research ◽  
Random Effect Models ◽  
Reduced Risk

The association between dietary fibre and colorectal cancer risk is controversial. This systematic review and meta-analysis was performed to determine fibre consumption reduced risk of colorectal cancer patients in western countries.The authors conducted a meta-analysis of published research articles on fibre consumption reduced risk of colorectal cancer patients in western countries published between January 2000 and January 2018 in the online article databases of PubMed, ProQuest and EBSCO. Pooled relative risk (PRR) were calculated with fixed and random-effect models. Data were processed using Stata version 14.2 (Stata Corporation). This study reviewed 405 articles. There are 7 studies conducted a systematic review and continued with Meta-analysis. The results showed fibre consumption reduced risk of colorectal cancer patients in western countries (RR = 0.83 [95% CI 0.75-0.93]). This analysis confirmed fibre consumption reduced risk of colorectal cancer patients in western countries.

scholarly journals LO84: The incidence of fall-related intracranial bleeding in older adults taking anticoagulants, antiplatelets and neither medication: a meta-analysis

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S38-S38
Author(s):  
K. de Wit ◽  
D. Nishijima ◽  
S. Mason ◽  
R. Jeanmonod ◽  
S. Parpia ◽  
...  
Keyword(s):  
Older Adults ◽  
Meta Analysis ◽  
Grey Literature ◽  
Random Effect ◽  
Intracranial Bleeding ◽  
Inclusion Criteria ◽  
Antiplatelet Medication ◽  
Cochrane Database ◽  
Random Effect Models ◽  
Anticoagulant Medication

Introduction: It is unclear whether anticoagulant or antiplatelet medications increase the risk for intracranial bleeding in older adults after a fall. Our aim was to report the incidence of intracranial bleeding among older adults presenting to the emergency department (ED) with a fall, among patients taking anticoagulants, antiplatelet medications, both medications and neither medication. Methods: This was a systematic review and meta-analysis, PROSPERO reference CRD42019122626. Medline, EMBASE (via OVID 1946 - July 2019), Cochrane, Database of Abstracts of Reviews of Effects databases and the grey literature were searched for studies reporting on older adults who were evaluated after a fall. We included prospective studies conducted in the ED where more than 80% of the cohort were 65 years or older and had fallen. We contacted study authors for aggregate data on intracranial bleeding in patients prescribed anticoagulant medication, antiplatelet medication and neither medication. Incidences of intracranial bleeding were pooled using random effect models, and I2 index was used to assess heterogeneity. Results: From 7,240 publication titles, 10 studies met inclusion criteria. The authors of 8 of these 10 studies provided data (on 9,489 patients). All studies scored low or moderate risk of bias. The pooled incidence of intracranial bleeding among patients taking an anticoagulant medication was 5.1% (n = 5,016, 95% Confidence Interval (CI): 4.1 to 6.3%) I2 = 42%, a single antiplatelet 6.4% (n = 2,148, 95% CI: 5.4 to 7.6%) I2 = 75%, both anticoagulant and antiplatelet medications 5.9% (n = 212, 95% CI: 1.3 to 13.5%) I2 = 72%, and neither of these medications 4.8% (n = 1,927, 95% CI: 3.5 to 6.2%) I2 = 50%. A sensitivity analysis restricted to patients who had a head CT in the ED reported incidences of 6.1% (n = 3,561, 95% CI: 3 to 8.3%), 8.4% (n = 1,781, 95% CI: 5.5 to 11.8%), 6.7% (n = 206, 95% CI 1.5 to 15.2%) and 6.6% (n = 1,310, 95% CI: 5.0 to 8.4%) respectively. Conclusion: The incidence of fall-related intracranial bleeding in older ED patients was similar among patients who take anticoagulant medication, antiplatelet medication, both and neither medication, although there was heterogeneity between study findings.

Correlation between Methylenetetrahydrofolate Reductase Polymorphisms and Hepatocellular Carcinoma: A Meta-Analysis

2019 ◽  
Vol 74 (3) ◽  
pp. 251-256 ◽  
Author(s):  
Hailong Su ◽  
Guo Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Polymorphisms ◽  
Methylenetetrahydrofolate Reductase ◽  
Meta Analysis ◽  
Random Effect ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Systematic Research ◽  
The Relationship ◽  
Random Effect Models

Background: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Objectives: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. Methods: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. Results: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43–0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29–0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06–1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29–0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. Conclusions: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

SAT0136 RELATIVE EFFICACY AND SAFETY OF TOFACITINIB, BARICITINIB, UPADACITINIB, AND FILGOTINIB, IN COMPARISON WITH ADALIMUMAB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A BAYESIAN NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1005.1-1005
Author(s):  
Y. H. Lee ◽  
G. G. Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Active Rheumatoid Arthritis ◽  
Response Rate ◽  
Meta Analysis ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
Randomized Controlled ◽  
Acr20 Response Rate

Background:Methotrexate (MTX), an effective disease-modifying antirheumatic drug (DMARD) [2], is the most widely used DMARD for the treatment of rheumatoid arthritis (RA). However, not all patients are responsive to the drug; 30% of the patients discontinue therapy within 1 year of commencing the treatment, usually because of the lack of efficacy or undesirable adverse effects Small-molecule Janus kinase inhibitors are clinically developed for the treatment of RA.Objectives:The aim of this study is to investigate the relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in comparison with adalimumab in patients with active RA and having inadequate responses to MTX.Methods:We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and adalimumab in RA patients having inadequate responses to MTX.Results:Four RCTs, comprising 5,451 patients, met the inclusion criteria. The baricitinib 4mg+MTX and upadacitinib 15mg+MTX group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the adalimumab 40mg+MTX group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that baricitinib 4mg+MTX had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by upadacitinib 15mg+MTX, tofacitinib 5mg+MTX, filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, and placebo+MTX. The upadacitinib 15mg+MTX and baricitinib 4mg+MTX groups showed significantly higher ACR50 and ACR70 response rates than adalimumab 40mg+MTX. In terms of Herpes zoster infection, the ranking probability based on the SUCRA indicated that placebo+MTX were likely to be the safest treatments, followed by filgotinib 200mg+MTX, filgotinib 100mg+MTX, adalimumab 40mg+MTX, tofacitinib 5mg+MTX, upadacitinib 15mg+MTX, and baricitinib 4mg+MTX. Regarding safety analysis, no statistically significant differences were found between the respective intervention groups.Conclusion:In RA patients with an inadequate response to MTX, baricitinib 4mg+MTX and upadacitinib 15mg+MTX showed the highest ACR response rates, suggesting a difference in efficacy among the different JAK inhibitors.References:[1]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, DeMasi R, Soma K, Zhang R, Takiya LJTL (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. 390:457-468[2]Taylor PC, Keystone EC, van der Heijde D et al (2017) Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 376:652-662[3]Fleischmann R, Pangan AL, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Zhou Y, Othman AA (2018) A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate. ARTHRITIS & RHEUMATOLOGY. WILEY 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, pp[4]Combe B, Kivitz A, Tanaka Y, van der Heijde D, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy J (2019) LB0001 EFFICACY AND SAFETY OF FILGOTINIB FOR PATIENTS WITH RHEUMATOID ARTHRITIS WITH INADEQUATE RESPONSE TO METHOTREXATE: FINCH1 PRIMARY OUTCOME RESULTS. BMJ Publishing Group Ltd, ppDisclosure of Interests:None declared

scholarly journals The Effect of Perinatal Fish Oil Supplement on Perinatal Depression: A Systemic Review and Meta- Analysis of Randomized Clinical Trials

2019 ◽  
pp. 262-271
Author(s):  
Helman S ◽  
Baker RB ◽  
Hassan M ◽  
Nafee T ◽  
Yang J ◽  
...  
Keyword(s):  
Fish Oil ◽  
Odds Ratio ◽  
Randomized Clinical Trials ◽  
Perinatal Depression ◽  
Meta Analysis ◽  
Systemic Review ◽  
Effect Measure ◽  
Central Registry ◽  
Fish Oil Supplementation ◽  
Reduced Risk

Background: Perinatal depression is a common complication of pregnancy and can have severe and long-termadverse effects on both mother and infant. Randomized controlled trials (RCT) assessing the effect of fish oilsupplements on perinatal depression have shown mixed results.Objectives: We performed a systematic review and meta-analysis to assess the effects of fish oil supplementation during pregnancy on perinatal depression.Methods: A comprehensive search of MEDLINE (PubMed), EMBASE, and Cochrane Central Registry were conducted in adherence with the PRISMA guideline. Only RCTs published in English from January 2000 to date were included. The participants were pregnant women receiving fish oil supplementation or placebo. Summary effect measure of each study was converted to a common effect measure (log odds ratio) and its variance was calculated to estimate the pooled odds ratio and its 95% confidence Interval using random Effects model. Heterogeneity was assessed used restricted maximum likelihood method.Results: Nine trials were included in our analysis (2,979 women). Prevention Cohort (n = 5): Fish oil supplementation during pregnancy was associated with reduced risk of developing perinatal depression (OR: 0.87; CI: 0.076 to 0.99; p = 0.03). Treatment Cohort (n = 4) Fish oil supplementation during pregnancy was associated with reduced risk of persistent perinatal depression during postpartum period but did not reach statistical significance.Conclusion: In conclusion, a meta-analysis of included RCTs data shows a significant reduction in incidences of perinatal depression in women who received fish oil supplements during pregnancy. However, there was no evidence for a similar effect among women diagnosed with perinatal depression or women with major depressive disorder.

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