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ID PMID Title PublicationDate abstract
24684408 Tocilizumab is clinically, functionally, and radiographically effective and safe either wi 2015 Jan OBJECTIVES: To explore the effectiveness and safety of tocilizumab (TCZ) with or without methotrexate (MTX) in active rheumatoid arthritis (RA) patients showing inadequate responses to DMARDs and/or TNF inhibitors in clinical practice. METHODS: We observed consecutive 115 RA patients initiating TCZ treatment in Keio University Hospital, dividing them into two groups with (TCZ + MTX group) or without MTX (TCZ group), and evaluated clinical, functional and structural outcomes besides safety at week 52. RESULTS: Overall mean age, RA duration, and DAS28-ESR were 55.4, 8.4 years, and 5.0, respectively. Proportions of the prior use of TNF inhibitors and concomitant MTX were 45.5% and 57.4%, respectively. Mean dose of concomitant MTX was 8.4 mg/week. Baseline characteristics were comparable between the groups. TCZ improved disease activity measured by DAS28-ESR to 2.1 at week 52 overall, without significant difference between the groups. Clinical (DAS28-ESR < 2.6), functional (HAQ-DI ≤ 0.5), and structural (ΔTSS ≤ 0.5) remission rates in the TCZ group and the TCZ + MTX group were 79.1%/63.8% (P = 0.10), 62.8%/54.4% (P = 0.40), and 70.0%/53.8% (P = 0.61), respectively. Retention rates were 81.0% in the TCZ + MTX group and 88.5% in the TCZ group (P = 0.47). The rate of serious adverse events was comparable between the groups. CONCLUSIONS: TCZ was clinically, functionally, and radiographically effective and safe either with or without low-dose MTX.
25760299 Interleukin-6 in rheumatoid arthritis - from the laboratory to the bedside. 2015 Rheumatoid arthritis (RA) is a common and debilitating disease. Expanded therapeutic options, targeting pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-6 (IL-6), have revolutionised RA treatment. To date, efficacy data shows superiority of IL-6 inhibition over placebo, conventional disease modifying anti-rheumatic drugs such as methotrexate, and TNF inhibition. Moreover, while demonstrating some key differences in the safety profile compared with TNF inhibition (e.g. hyperlipidemia and neutropenia), these safety concerns have not, at least to date, been found to cause clinically significant adverse outcomes. Other safety parameters, such as infection and malignancy rates have been found to be comparable between IL-6 and TNF inhibition. This review explores the biology and clinical applications of IL-6 inhibition in the management of RA.
25832554 Effects of Concomitant Methotrexate on Large Joint Replacement in Patients With Rheumatoid 2015 Oct OBJECTIVE: To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. METHODS: A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias. RESULTS: Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6-8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20-0.65). Additionally, propensity score-matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032). CONCLUSION: Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.
25803089 Effect of Withania somnifera (Ashwagandha) root extract on amelioration of oxidative stres 2015 Jun BACKGROUND: Rheumatoid arthritis is an inflammatory autoimmune disorder. Withania somnifera Dunal (Solanaceae) (WS), is a common medicinal plant used in traditional systems of medicine for the treatment of arthritis, and is an ingredient of anti-arthritic polyherbal formulations such as Habb-e-Asgand® and Arthritin™. In the present study, we evaluated the antioxidant and anti-arthritic activity of aqueous extract of WS root (WSAq) in collagen-induced arthritic (CIA) rats. METHODS: CIA rats were treated by using three doses of WSAq (100, 200, 300 mg/kg b. wt., orally) and methotrexate (MTX, 0.25 mg/kg b. wt. i.p.) as a standard reference drug for 20 days. The anti-arthritic effect was assayed by measuring the arthritic index, autoantibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (a-CCP), anti-nuclear antibody (ANA), anti-collagen type II antibody (a-CII) and inflammatory marker like C-reactive protein (CRP). The oxidative stress parameters were also measured. RESULTS: Treatment with WSAq resulted in a dose-dependent reduction in arthritic index, autoantibodies and CRP (p < 0.05) with maximum effect at dose of 300 mg/kg b. wt. and the results were comparable to that of MTX-treated rats. Similarly, oxidative stress in CIA rats was ameliorated by treatment with different doses of WSAq, as evidenced by a decrease in lipid peroxidation and glutathione-S-transferase activity and an increase in the glutathione content and ferric-reducing ability of plasma (p < 0.05). CONCLUSIONS: The results showed that WSAq exhibited antioxidant and anti-arthritic activity and reduced inflammation in CIA rats and suggests the potential use of this plant in the treatment of arthritis.
27374036 Left ventricular function in rheumatoid arthritis during anti-TNF-α treatment: a speckle 2016 Jun 22 AIM: Rheumatoid arthritis (RA) shows a high risk for cardiovascular disease, including heart failure. Although TNF-α has been implicated in the pathogenesis of myocardial remodelling, TNF-α inhibition did not show any efficacy in patients with advanced heart failure and should be contraindicated in RA with cardiac complications. We aimed to assess global left ventricular (LV) systolic function using global longitudinal strain (GLS) as a measure of myocardial deformation, in a group of RA patients before and during anti-TNF-α treatment. METHODS: 13 patients (female:male 7:6) affected by RA were prospectively followed for one year during anti TNF-α treatment. Every subject underwent echocardiography before starting anti-TNF-α drugs and after one year of treatment, to evaluate LV ejection fraction (EF), telediastolic diameter, telediastolic volume and global longitudinal strain (GLS) that was calculated using 2D speckle tracking as the mean GLS from three standard apical views (2, 3 and 4 -chambers). The patients showed a mean age of 43 years at RA onset (SD: 13) and a mean follow-up of 7.3 years (SD: 4.8). Steroid and methotrexate were used in 84.6% and 100%, respectively, in association with etanercept (6 cases), adalimumab (4 cases) and infliximab (3 cases). RESULTS: Patients globally showed a normal EF before and after one year of treatment (mean: 65% and 65.7%, respectively). GLS did not differ before or after anti-TNF-α treatment (mean: -15.8% and -16.7%, respectively). CONCLUSION: Anti-TNF-α treatment did not significantly modify myocardial contractility after 12 months.
27213997 A survey on the medication adherence to methotrexate among rheumatoid arthritis patients t 2016 Jul OBJECTIVES: Methotrexate (MTX) is the most widely used co-therapy among rheumatoid arthritis (RA) patients using biological disease-modifying anti-rheumatic drugs (bDMARDs). However, adherence to MTX treatment remains a concern with estimates of adherence ranging from 59 to 63%. The objective of this study was to assess the self-reported use and adherence to MTX among RA patients treated with self-administered bDMARDs. METHODS: An electronic questionnaire survey was conducted in 68 community pharmacies in Finland. To be included in the present study patients had to be at least 18 years old, be currently using a self-administered bDMARD and be diagnosed with RA. The results are presented as medians with their respective interquartile ranges (IQR) or percentages. RESULTS: Of the 158 pharmacy customers asked to participate, 135 (85%) consented to complete the questionnaire. The included respondents were predominantly female (72%) with a median age of 55 (IQR 44-65) and rheumatic activity of 3 out of 10 (IQR 2-6.5). The majority (91%) of the included respondents were using TNF-inhibitors and 27% of all patients were on biologic monotherapy. MTX was currently used by 45% of the respondents while 50% were past users. Of the current MTX users, 6.8% identified themselves moderately non-adherent to the treatment. MTX-related adverse events were important factors associated with nonadherence and discontinuation of the treatment. CONCLUSIONS: Only 45% of the respondents were currently using MTX co-therapy, but the ones who did were adherent to their treatment. Self-reported adherence may however be subject to social desirability bias and recall bias.
27188329 Differential response of serum amyloid A to different therapies in early rheumatoid arthri 2016 May 17 BACKGROUND: The aim was to compare the effect of etanercept (ETN) and conventional synthetic disease-modifying anti-rheumatic drug (DMARD) therapy on serum amyloid A (SAA) levels and to determine whether SAA reflects rheumatoid arthritis (RA) disease activity better than C-reactive protein (CRP). METHODS: We measured SAA and CRP at baseline, 24, 48, and 102 week follow-up visits in 594 patients participating in the Treatment of early RA (TEAR) study. We used Spearman correlation coefficients (rho) to evaluate the relationship between SAA and CRP and mixed effects models to determine whether ETN and methotrexate (MTX) treatment compared to triple DMARD therapy differentially lowered SAA. Akaike information criteria (AIC) were used to determine model fits. RESULTS: SAA levels were only moderately correlated with CRP levels (rho = 0.58, p < 0.0001). There were significant differences in SAA by both visit (p = 0.0197) and treatment arm (p = 0.0130). RA patients treated with ETN plus MTX had a larger reduction in SAA than patients treated with traditional DMARD therapy. Similar results were found for serum CRP by visit (p = 0.0254) and by treatment (p < 0.0001), with a more pronounced difference than for SAA. Across all patients and time points, models of the disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) using SAA levels were better than models using CRP; the ΔAIC between the SAA and CRP models was 305. CONCLUSIONS: SAA may be a better biomarker of RA disease activity than CRP, especially during treatment with tumor necrosis factor (TNF) antagonists. This warrants additional studies in other cohorts of patients on treatment for RA. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00259610 , Date of registration: 28 November 2005).
26090499 Methotrexate, Cyclosporine A, and Biologics Protect against Atherosclerosis in Rheumatoid 2015 INTRODUCTION: The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate--MTX) in protecting against atherosclerosis. OBJECTIVES: The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques. PATIENTS AND METHODS: 317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques. RESULTS: CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ≥ 20 mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ≥ 20 mg/wk, biologics, or CsA were found. CONCLUSIONS: We found a beneficial effect of MTX ≥ 20 mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX.
25794569 Cost-utility analysis of tocilizumab monotherapy in first line versus standard of care for 2015 Sep The study aims to evaluate the cost-effectiveness of adding tocilizumab (TCZ) first line to a treatment sequence for patients with active rheumatoid arthritis (RA), who had an inadequate response to one or more traditional synthetic disease-modifying antirheumatic drugs (DMARDs) and are intolerant to methotrexate (MTX), or in whom continued treatment with MTX is considered inappropriate. An individual simulation model was applied to project lifetime costs and outcomes for 10,000 patients from a payer's perspective. The analysis compared the standard treatment pathway (STP) with a similar pathway, where treatment was initiated with TCZ. QALYs were used as primary efficacy outcomes. Efficacy data were obtained from the ADACTA trial and a network meta-analysis. Clinical practice standards were derived from an expert panel of Greek rheumatologists. Results indicate that a treatment sequence starting with TCZ yields 1.17 more QALYs (9.38 vs. 8.21) at an additional cost of €3,744 (€119,840 vs. €86,096) compared with the STP. The incremental cost-effectiveness ratio was €28,837/QALY gained. Probabilistic sensitivity analysis confirms robustness of these findings as consistently below a threshold of €45,000. The results of the analysis suggest that TCZ, when used as a first-line biologic monotherapy, can be a cost-effective treatment option for the management of active RA in patients in need of biologic monotherapy.
27455886 Oral Methotrexate in split dose weekly versus oral or parenteral Methotrexate once weekly 2018 May OBJECTIVE: To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2-3 days' interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally. MATERIALS AND METHODS: One hundred and thirty-five patients fulfilling the American College of Rheumatology (ACR) 2010 criteria for RA, on 7.5 mg of MTX weekly orally, with the Simplified Disease Activity Index (SDAI) > 11 were enrolled for a 24-week period. Patients were randomly divided into three groups and were given MTX: Group 1 7.5 mg twice or thrice weekly orally, Group 2 15 mg or 22.5 mg in a single dose weekly orally and Group 3 15 mg or 22.5 mg in a single dose weekly as an intramuscular injection. The primary outcomes were low disease activity (LDA) and mean change in SDAI at week 24, whereas secondary outcomes included remission, adverse events and compliance. RESULTS: At week 24, adherence to treatment was maximum in Group 1, 69% (P = 0.09). In intention-to-treat analysis at 24 weeks, Group 1, 49%, Group 2, 36% and Group 3, 47% achieved LDA (P = 0.4). There was significant difference in mean change in SDAI at week 24 from baseline (P = 0.008) among the groups. Group 3 patients were more uncomfortable with the mode of administration of MTX (P = 0.003). There was no significant difference in adverse events. CONCLUSION: Oral split doses of MTX are better than an oral single dose and similar to parenteral MTX in terms of efficacy.
26354409 Survey on management strategies of rheumatoid arthritis in Saudi Arabia: a Saudi Society f 2017 Sep AIM: Currently there are no national recommendation guidelines for the management of rheumatoid arthritis (RA) in Saudi Arabia, which has led to a lack of standard of care. The aim of this study is to explore RA management strategies in practicing rheumatologists in Saudi Arabia. METHODS: A 38 questions survey was designed using an electronic website. The survey was distributed through the official email of the Saudi Society for Rheumatology. Rheumatologists with at least 1 year of experience were included. Descriptive analysis was used to report demographics and participants' answers. Chi-square and Fischer's exact test were used to evaluate the relation between the characteristics of participants and their answers. RESULTS: Out of 120 registered practicing adult rheumatologists, 54 (45%) completed the survey. The majority were male 31 (57.4%) and Saudis 36 (66.7%). Forty-two participants (77.8%) use clinical outcome measures in daily clinical practice to guide treatment decisions with the majority using the Disease Activity Score of 28 joints (61.1%). Quality of life measures were used by 22 (40.7%) participants with statistically significant male predominance (P = 0.043). Time consumption was the most important cause for not using any outcome measures. Thirteen (24.1%) and 17 (31.5%) participants do not use parenteral methotrexate and leflunomide, respectively, because of unavailability in the hospital formulary. Nine (16.7%) and 38 (70.37%) participants do not see a role for tofacitinib and biosimilars, respectively, in the management of RA. CONCLUSION: This survey has highlighted many areas of improvement in the practice of rheumatologists in Saudi Arabia and should be the focus of future educational activities.
27609026 Methotrexate is not associated with increased liver cirrhosis in a population-based cohort 2016 Sep 9 A few studies have shown that methotrexate (MTX) use exacerbates liver fibrosis and even leads to liver cirrhosis in rheumatoid arthritis (RA) patients, although the risk is low compared to psoriatics. We therefore conducted a population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic hepatitis C (CHC)-related cirrhosis among RA patients. We analyzed data from the National Health Insurance Research Database in Taiwan and identified 450 incident cases of RA among CHC patients (255 MTX users and 195 MTX non-users) from January 1, 1998 to December 31, 2007. After a median follow-up of more than 5 years since the diagnosis of CHC, a total of 55 (12%) patients developed liver cirrhosis. We did not find an increased risk of liver cirrhosis among CHC patients with long-term MTX use for RA. Furthermore, there was no occurrence of liver cirrhosis among the 43 MTX users with a cumulative dose ≧3 grams after 108 months of treatment. In conclusion, our data showed that long-term MTX use is not associated with an increased risk for liver cirrhosis among RA patients with CHC. However, these results should be interpreted with caution due to potential bias in the cohort.
25438985 Patients with rheumatoid arthritis have better functional and working ability but poorer g 2015 May OBJECTIVES: Better treatment strategies and therapeutic options have changed the treatment of rheumatoid arthritis (RA) during the past decade. Our objective was to examine clinical and patient-reported outcomes in patients with RA treated in 1998-99 and 2011-12. METHOD: The cross-sectional observational study included 303 consecutive outpatients (n = 103 in 1998-99 and n = 200 in 2011-12) from the same outpatient clinic. Patient questionnaires included patients' sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, the Nottingham Health Profile (NHP) for health-related quality of life (HRQoL), self-reported general health (GH), and operations performed due to RA. A clinical examination was conducted for all patients. Comorbidities according to the Charlson Comorbidity Index (CCI), anti-rheumatic drugs and medications were recorded and the HAQ and NHP dimensions calculated. The results from these two patient cohorts were compared. RESULTS: The cohorts were comparable with regard to age, sex, and RA duration while the patients in the 2011-12 cohort were less often seropositive for rheumatoid factor (RF), had a better socioeconomic situation, better functional and working ability, and a decreased rate of RA surgery. The patients in 2011-12 had higher comorbidities and poorer GH while the HRQoL dimensions did not differ between the cohorts except for better mobility in 2011-12. Methotrexate (MTX) and combinations of conventional anti-rheumatic drugs were more frequently used in 2011-12. Biologicals were used only in 2011-12. CONCLUSIONS: According to our results, more active anti-rheumatic therapy coincides with better RA-related outcomes. However, the result was the opposite with regard to overall health and comorbidities. Is this a new challenge in the treatment RA?
26591359 [Effect of Xinfeng Capsule on Lipoprotein Metabolism of Rheumatoid Arthritis Patients]. 2015 Sep OBJECTIVE: To explore the effect of Xinfeng Capsule (XC) on lipoprotein metabolism of rheumatoid arthritis (RA) patients. METHODS: Totally 180 RA patients were assigned to the experimental group and the control group by random digit table, 90 in each group. Patients in the experimental group took XC (three pills each time, three times daily), while those in the control group took Methotrexate Tablet (four tablets each time, once per week). One month consisted of one therapeutic course and all patients were treated for two therapeutic courses. A healthy control group consisting of 60 patients was also set up. Changes of lipoprotein indices, clinical efficacy, lipid metabolism, joint symptoms and signs, activity indicators were observed, and correlation analyses were performed. RESULTS: Compared with the healthy control group, expression levels of prealbumin (PA), globulin (GLO), high-density lipoprotein (HDL), apolipoprotein Al (Apo-A1) were lowered in RA patients (P <0. 05, P <0. 01). Correlation analyses showed that PA was negatively correlated with joint tenderness, morning stiffness time, disease activity score (DAS-28), C-reactive protein (CRP), interleukin (IL)-6, respectively. Total protein (TP) was negatively correlated with joint tenderness. GLO was negatively correlated with joint tenderness and DAS-28. HDL was negatively correlated with erythrocyte sedimentation rate (ESR) and endothelin (ET)-1. Apo-Al was negatively correlated with joint pain; Apo-B was negatively correlated with CRP; LDL was negatively correlated with morning stiffness time (P <0. 05, P <0. 01). Compared with before treatment, expression levels of PA, HDL, Apo-A1 , Apo-B, and serum IL-10 contents increased, and expression levels of ESR, CRP, IL-6, ET-1 , joint pain, joint swelling, morning stiffness time, and DAS-28 decreased in the experimental group (P <0. 05, P <0. 01). PA increased more after treatment than before treatment in the control group (P <0. 01). There was statistical difference in joint symptoms (except joint tenderness) and activity indices (except ET-1) in the control group (P <0. 05, P <0. 01). Compared with the control group after treatment, PA and HDL increased, ET-1 and duration of morning stiffness decreased in the experimental group (all P <0. 05). CONCLUSIONS: Lipoprotein metabolic disorder exists in RA patients, and it is associated with disease activity. XC could obviously improve lipoprotein metabolism and joint symptoms.
25800638 Early therapeutic intervention with methotrexate prevents the development of rheumatoid ar 2015 OBJECTIVES: To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers. METHODS: The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year. RESULTS: The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups. CONCLUSIONS: This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.
26345515 Protective Effects of Simvastatin and Hesperidin against Complete Freund's Adjuvant-Induce 2015 BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a disabling autoimmune disease for which most current treatments cause massive complications, thereby limiting treatment dose and duration. The anti-arthritic effects of the 3-hydroxy-3-metylglutary-CoA reductase inhibitor, simvastatin, and the natural flavonoid, hesperidin, were investigated against complete Freund's adjuvant-induced RA in rats. METHODS: A normal control group, an arthritis control group, 2 reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and 2 treatment groups receiving simvastatin (0.5 mg/kg/day) and hesperidin (200 mg/kg/day) were included in the study. Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) as specific rheumatoid biomarkers, serum immunoglobulin G (IgG) and antinuclear antibody (ANA) as immunological biomarkers, serum tumor necrosis factor-alpha and interleukin-10 as immunomodulatory cytokines, serum myeloperoxidase (MPO) and C-reactive protein as inflammatory biomarkers, and malondialdehyde (MDA) and glutathione (GSH) as oxidative stress biomarkers were assessed, supported by joint and spleen histopathological study. RESULTS: Simvastatin significantly improved all the measured biomarkers, with MMP-3, COMP, and GSH restored to normal levels. Hesperidin significantly improved all the measured biomarkers, with COMP, IgG, ANA, MPO, MDA and GSH restored to normal levels. CONCLUSION: Simvastatin and hesperidin may be promising protective agents against RA through immunomodulatory, anti-inflammatory and antioxidant potentials.
27523470 Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate. 2017 Nov Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome.
25536122 Outcomes related to methotrexate dose and route of administration in patients with rheumat 2015 Mar OBJECTIVES: Methotrexate (MTX) is considered the 'anchor drug' in the therapy of rheumatoid arthritis (RA), yet many physicians do not optimise MTX regimens in spite of high RA disease activity. The recent development of an auto-injector for the subcutaneous (subQ) administration of MTX has prompted re-evaluation of MTX utilisation. The purpose of this systematic literature review is to determine the optimal dose, drug level, and route of administration for MTX in the context of relevant pharmacokinetics and pharmacogenomics. METHODS: A systematic literature review was performed in Medline searching specifically for randomised controlled trials, systematic reviews, case control and cohort studies evaluating outcomes related to MTX dose and route of administration. Articles fulfilling these inclusion criteria were reviewed. Data on MTX dose, route of administration, clinical response, drug levels and adverse events were evaluated. RESULTS: Our search identified 420 articles of which 6 were eligible for inclusion using the above criteria. These included 2 systematic reviews, 2 randomised open label trials, one longitudinal study and one retrospective cohort study. CONCLUSIONS: Efficacy and toxicity for MTX appear related to absorbed dose of MTX, not to route of administration. While bioavailability is greater for parenteral MTX, there is no evidence yet that splitting the oral dose of MTX is less advantageous, less safe or less tolerable than administering parenteral MTX. However, there appear to be modest benefits in beginning with higher doses of MTX, and switching to parenteral MTX when the clinical response to an oral dose is inadequate.
25948343 The rate of decrease in the disease activity of rheumatoid arthritis during treatment with 2015 OBJECTIVE: The aim of this study was to analyze the efficacy of adalimumab (ADA) in patients with rheumatoid arthritis treated with or without methotrexate (MTX) and determine impact of the MTX dose. METHODS: Pearson's product-moment correlation coefficient was used to assess the correlations between the improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a dose of <8 mg/week, 8 mg/week and >8 mg/week. PATIENTS: ADA therapy was initiated in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX dose was 9.6 ± 2.6 mg/week, and the patients were followed for 24 weeks. RESULTS: The mean DAS28-ESR scores at baseline and week 24 were 4.6 ± 1.3 and 2.7 ± 1.2 in the 60 patients treated with MTX and 4.5 ± 1.0 and 4.2 ± 1.5 in the eight patients treated without MTX, respectively. Clinical remission was achieved in 48% and 25% of the patients, respectively, by week 24. Moreover, 90.0% of the patients taking MTX continued to receive ADA until week 24, while 50.0% of the patients not taking MTX continued to receive ADA until week 24. Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores decreased rapidly from 4.4 ± 1.2 at baseline to 3.2 ± 1.1 at week 4 and further decreased to 2.4 ± 1.0 at week 24. Meanwhile, clinical remission was achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of those receiving MTX at a dose of ≤8 mg/week. A significant correlation was noted between the improvement in the DAS-ESR score and the MTX dose. CONCLUSION: In this study population, enhanced clinical efficacy of ADA was achieved in combination with the administration of a sufficient dose of MTX, determined to be >8 mg/week.
27989589 Efficacy of triple association methotrexate, sulfasalazine and hydroxychloroquine in early 2017 Oct OBJECTIVES: To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a biologic DMARD (bDMARD) in the treatment of early rheumatoid arthritis. METHODS: A systematic literature search was performed using the PubMed and Cochrane databases, and abstracts presented at rheumatology scientific meetings until December 2013. Randomized controlled trials comparing the efficacy and the safety of biologic DMARD with the triple combination were included. Outcome measures were Van der Heijde modified Sharp score (SHS), remission rate, ACR criteria response, adverse events. RESULTS: A total of 1225 abstracts were screened. We extracted data from 5 trials including patients (515 in the triple combination group and 710 in the bDMARD group). We showed higher ACR70 response (OR=1.79, 95% CI [1.17, 2.72]) in patients treated with bDMARDs, whereas radiological progression was not different from patient with triple combination (OR=1.10, 95% CI [-0.04, 0.28]). At year 2, ACR70 response and remission rate, the results were similar in both groups with respectively OR=1.44 (95% CI [0.86, 2.43]) and SMD=0.45 (95% CI [0.17, 0.72]). The proportion of serious adverse events was similar in both groups OR=1.02 (95% CI [0.68, 1.52], P=0.92, I(2)=0%). Gastro-intestinal adverse events were higher in the triple combination group (OR=1.75, 95% CI [0.73, 4.21], P=0.21, I(2)=75%). Infectious adverse events were more frequent in the bDMARD group (OR=0.50, 95% CI [0.35, 0.70], P<0.0001, I(2)=36%). CONCLUSION: Biological treatment seems to be more efficient than triple combination in terms of radiological progression in RA with inadequate response to methotrexate.