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ID PMID Title PublicationDate abstract
31813863 Effectiveness of methotrexate in combination therapy in a rat collagen-induced arthritis m 2019 Sep This study was to investigate the effect of methotrexate in combination therapy by the characteristic cytokine in Th17 cells and the frequency of Tregs, which involved in the induction and pathological progress of rheumatoid arthritis (RA). The collagen-induced arthritis rats were treated with methotrexate + prednisone, methotrexate + disease-modifying rheumatic drugs (DMARDs) and methotrexate + TNFi, respectively. The following parameters were observed to evaluate three treatments: the frequency and function of Th17 cells and Tregs, the scores of X-rays, H&E staining and immunohistochemistry. For rats starting methotrexate + prednisone (low doses), the frequency and suppressive function of Th17 cells decreased while the frequency of Tregs increased, which were the same in methotrexate + TNFi. Immunohistochemical in the pathological sections of ankle joint showed the same results. The effect of methotrexate + DMARDs treatment was slightly inferior to the other combination therapies. In summary, rats treated with methotrexate + prednisone can achieve high level of Tregs and low level of Th17 cells and IL-17. Low doses of glucocorticoid suggesting a critical role in the pathogenesis of rheumatoid arthritis may have the similar effect as DMARDs.
31297603 [Long-term trends in rheumatology care : Achievements and deficits in 25 years of the Ger 2019 Oct BACKGROUND: Since 1993, data on the care and quality of life of patients with inflammatory rheumatic diseases have been collected in the German National Database (NDB) of the regional collaborative rheumatology centers. OBJECTIVE: In this review long-term trends on treatment, disease activity and gainful employment of the most common inflammatory rheumatic diseases are presented and the most important analyses from 25 years of the NDB are summarized. METHODS: Between 15 and 17 rheumatological institutions take part in the core documentation and once a year collect data from a total of more than 10,000 patients. The rheumatologists document the disease status and care, the patients report on their state of health and the effects of the disease. RESULTS: The biologics era at the beginning of the twenty-first century has led to changes in the therapeutic spectrum of most inflammatory rheumatic diseases, especially in rheumatoid arthritis and ankylosing spondylitis. Some basic therapies formerly used are hardly used anymore and glucocorticoids are used less frequently. Methotrexate has remained the standard therapy for rheumatoid arthritis over the years. Nowadays, nearly 30% of patients with rheumatoid arthritis receive treatment with biologics. Disease activity, functional and social restrictions have decreased across all diseases. CONCLUSION: The improved health status of many patients with rheumatic diseases confirms the high level of care provided by the rheumatism centers involved in the NDB. The increasing specification of measuring instruments and the standardization of documentation systems are major challenges that the NDB will have to face in the coming years if it is to remain in the digital age.
31393189 Investigation of the predictors of the response to Iguratimod therapy: A post-hoc analysis 2020 Jul Objectives: The treatment response according to patient disease activity during Iguratimod therapy for rheumatoid arthritis has not been sufficiently assessed. A post-hoc analysis of post-marketing surveillance was performed. The treatment effect was evaluated using the European League against Rheumatism (EULAR) response criteria.Methods: Disease Activity Score (DAS) 28 was assessed at various time points. Patients showing a moderate or good response according to the EULAR response criteria at 24 weeks after the start of Iguratimod therapy were considered Responders. Propensity score matching was also performed, after which the factors with the greatest effect on the treatment evaluation were investigated.Results: The mean DAS28 at the start of administration and after 24 weeks was 4.31 and 2.52, respectively, in the Responder and 3.48 and 3.48, respectively, in the Non-responder. After propensity score matching for patient characteristics, the primary factors found to be related to being a Responder were concomitant use of methotrexate (MTX) with Iguratimod, and prior treatment with MTX before the start of Iguratimod.Conclusion: As factors related to the treatment effect, the concomitant use of MTX may contribute to achieving a better effect, and this study has shown that real-world are consistent with the results of clinical trials.
31311386 Addition or removal of concomitant methotrexate alters adalimumab effectiveness in rheumat 2019 Sep Objective: Randomized trials have shown that concomitant methotrexate (MTX) augments the effectiveness of tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA), but its benefit in psoriatic arthritis (PsA) has not been demonstrated. The goal of this study was to examine whether the impact of concomitant MTX on therapeutic outcomes in patients with PsA was similar to its effects in RA. Methods: We used data from highly comparable and concurrent observational studies of patients with PsA (N = 1424) or RA (N = 3148) who initiated adalimumab therapy during routine clinical care. The 28-joint Disease Activity Score (DAS28) and patient-reported pain scores were evaluated in patients who received 24 months of continuous treatment with adalimumab monotherapy or adalimumab + MTX and in patients who initiated or stopped concomitant MTX during ongoing adalimumab therapy. Results: Twenty-four months of continuous treatment with adalimumab + MTX was superior to adalimumab monotherapy in RA patients, while no significant difference was observed in patients with PsA. RA patients who added MTX during the study showed significant individual improvements in DAS28 and pain scores at 6 months after the change in therapy, while those who removed MTX had slight increases in disease activity. In contrast, in patients with PsA, neither initiation nor removal of MTX during continuous adalimumab therapy had a significant effect on therapeutic outcomes. Conclusion: Addition of MTX to adalimumab confers further therapeutic benefit in patients with RA, but not in those with PsA, suggesting differences in MTX effects in these two patient populations. Clinicaltrials.gov NCT01078090, NCT01077258, NCT01111240.
30299241 Efficacy of tocilizumab monotherapy after response to combined tocilizumab and methotrexat 2019 May OBJECTIVES: The aim of the JUST-ACT study was to assess whether the add-on effect of tocilizumab (TCZ) to background methotrexate (MTX) observed in MTX-inadequate responders with active rheumatoid arthritis (RA), would be sustained when MTX is withdrawn. METHODS: A double-blind, parallel-group, phase 3 study in biologic-naïve RA patients with a disease activity score 28 (DAS28)>3.2 despite MTX which were treated with TCZ+MTX for an initial 16-week period. Patients who at week 16 achieved low disease activity (LDA) (DAS28≤3.2) were randomised to continue with TCZ+MTX or switch to TCZ + placebo (PBO) for an additional 12 weeks. The primary endpoint was the change in DAS28-ESR from the randomisation at week 16 to week 28. Non-inferiority was confirmed if the upper limit of the two-sided 95%CI for the treatment difference between TCZ+MTX and TCZ monotherapy groups was lower than the selected non-inferiority margin of 0.6. RESULTS: 261 patients completed the first 16 weeks of TCZ+MTX treatment and 165 were randomised (83 to TCZ+MTX and 82 to TCZ+PBO). For the primary endpoint, the adjusted treatment difference (95% CI) in mean change of DAS28-ESR was -0.06 (-0.40 to 0.27), and therefore the non-inferiority of switching to TCZ monotherapy versus continuing with TCZ+MTX was demonstrated. In both treatment groups, the percentage of patients in clinical remission from 16 to 28 weeks was similar as were the improvements in disease activity, functional disability and quality of life. CONCLUSIONS: In MTX non-responder patients achieving LDA with TCZ+MTX, switching to TCZ monotherapy is non-inferior to continuing the combination.
31213399 Targeting CD34(+) cells of the inflamed synovial endothelium by guided nanoparticles for t 2019 Sep Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34 (+) endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures were made of poly-lactic acid, poly-caprolactone, and PEG and then coated with a synovial homing peptide. Immunofluorescence analysis clearly demonstrated their capacity to selectively address CD34 (+) endothelial cells in synovial tissue obtained from human, mouse, and rat. Biodistribution studies in two different animal models of rheumatoid arthritis (antigen-induced arthritis/AIA and collagen-induced arthritis/CIA) confirmed the selective accumulation in inflamed joints but also evidenced the capacity of tBNP to detect early phases of the disease and the preferential liver elimination. The therapeutic effect of methotrexate (MTX)-loaded tBNPs were studied in comparison with conventional MTX doses. MTX-loaded tBNPs prevented and treated CIA and AIA at a lower dose and reduced administration frequency than MTX. Moreover, MTX-loaded tBNP showed a novel mechanism of action, in which the particles target and kill CD34 (+) endothelial progenitors, preventing neo-angiogenesis and, consequently, synovial inflammation. tBNPs represent a stable and safe platform to develop highly-sensitive imaging and therapeutic approaches in RA targeting specifically synovial neo-angiogenesis to reduce local inflammation.
31721697 Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applica 2019 Increasing age is a strong, independent risk factor for atherosclerosis and cardiovascular disease. Key abnormalities driving cardiovascular risk in old age include endothelial dysfunction, increased arterial stiffness, blood pressure, and the pro-atherosclerotic effects of chronic, low-grade, inflammation. The identification of novel therapies that comprehensively target these alterations might lead to a major breakthrough in cardiovascular risk management in the older population. Systematic reviews and meta-analyses of observational studies have shown that methotrexate, a first-line synthetic disease-modifying anti-rheumatic drug, significantly reduces cardiovascular morbidity and mortality in patients with rheumatoid arthritis, a human model of systemic inflammation, premature atherosclerosis, and vascular aging. We reviewed in vitro and in vivo studies investigating the effects of methotrexate on endothelial function, arterial stiffness, and blood pressure, and the potential mechanisms of action involved. The available evidence suggests that methotrexate might have beneficial effects on vascular homeostasis and blood pressure control by targeting specific inflammatory pathways, adenosine metabolism, and 5' adenosine monophosphate-activated protein kinase. Such effects might be biologically and clinically relevant not only in patients with rheumatoid arthritis but also in older adults with high cardiovascular risk. Therefore, methotrexate has the potential to be repurposed for cardiovascular risk management in old age because of its putative pharmacological effects on inflammation, vascular homeostasis, and blood pressure. However, further study and confirmation of these effects are essential in order to adequately design intervention studies of methotrexate in the older population.
31474599 Comparative Persistence of Methotrexate and Tumor Necrosis Factor Inhibitors in Rheumatoid 2020 Jun 1 OBJECTIVE: The role of methotrexate (MTX) for the treatment of spondyloarthritis (SpA) remains uncertain. Aims were to compare MTX and tumor necrosis factor inhibitor (TNFi) persistence in spondyloarthritis versus rheumatoid arthritis (RA) and to determine whether concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use is associated with improved TNFi persistence in SpA. METHODS: This retrospective cohort study using Optum's deidentified Clinformatics Data Mart Database 2000-2014 identified patients with RA, psoriatic arthritis (PsA), and ankylosing spondylitis (AS) without prior biologic use who were initiating MTX or a TNFi. Cox proportional hazards models compared time to medication discontinuation over the next 2 years between patients with RA, PsA, or AS, adjusting for potential confounders. In similar analyses stratified by disease, Cox models were used to assess whether concomitant use of csDMARD was associated with TNFi persistence. RESULTS: We identified 31,527 MTX initiators (26,708 RA, 2939 PsA, 1880 AS) and 34,651 TNFi initiators (24,134 RA, 6705 PsA, 3812 AS). MTX was discontinued sooner in patients with PsA [adjusted HR (aHR) 1.10, 95% CI 1.04-1.16] and AS (aHR 1.23, 1.16-1.31) versus RA, while TNFi were discontinued at similar rates in RA and AS and discontinued later in PsA (aHR 0.93, 0.89-0.97). Concomitant use of MTX (compared to no csDMARD) was associated with lower rates of TNFi discontinuation in RA (aHR 0.85, 0.80-0.89), PsA (aHR 0.81, 0.74-0.89), and AS (aHR 0.79, 0.67-0.93). CONCLUSION: MTX discontinuation occurs sooner in patients with PsA and AS versus RA. Concomitant use of MTX with a TNFi, however, is associated with improved TNFi persistence in all 3 diseases.
31390271 Discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis 2020 May Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combination therapy with tocilizumab (TCZ) plus MTX.Methods: This multicenter, open-label, uncontrolled, prospective study included RA patients maintaining low disease activity (Clinical Disease Activity Index (CDAI) ≤10) for ≥12 weeks with TCZ plus MTX. Methotrexate was discontinued following 12 weeks of biweekly administration while continuing TCZ therapy. The primary endpoint was the proportion of patients maintaining low disease activity with no flare at week 36.Results: A total of 49 patients completed 36 weeks of therapy. The proportion of patients maintaining low disease activity at week 36 was 75.5%. The lower limit of the 95% confidence interval exceeded the assumed threshold response rate of 60%, demonstrating the clinical feasibility of MTX discontinuation. The prevalence of gastroesophageal reflux disease, defined as a Frequency Scale for Symptoms of Gastroesophageal reflux disease score ≥8, significantly decreased from week 0 to 12 (27.1-18.4%; p= .025).Conclusion: Discontinuation of concomitant MTX is clinically feasible for maintaining low disease activity, and may be beneficial from the perspective of reducing gastrointestinal symptoms in Japanese RA patients treated with TCZ. Trial registration number: UMIN000021247.
31407089 Long-term trends in rheumatology care : Achievements and deficits in 25 years of the Germ 2019 Dec BACKGROUND: Since 1993, data on the care and quality of life of patients with inflammatory rheumatic diseases have been collected in the German National Database (NDB) of the regional collaborative rheumatology centers. OBJECTIVE: In this review long-term trends on treatment, disease activity and gainful employment of the most common inflammatory rheumatic diseases are presented and the most important analyses from 25 years of the NDB are summarized. METHODS: Between 15 and 17 rheumatological institutions take part in the NDB and once a year collect data from a total of more than 10,000 patients. The rheumatologists document the disease status and care, the patients report on their state of health and the effects of the disease. RESULTS: The biologics era at the beginning of the twenty-first century has led to changes in the therapeutic spectrum of most inflammatory rheumatic diseases, especially in rheumatoid arthritis and ankylosing spondylitis. Some basic therapies formerly used are hardly used anymore and glucocorticoids are used less frequently. Methotrexate has remained the standard therapy for rheumatoid arthritis over the years. Nowadays, nearly 30% of patients with rheumatoid arthritis receive treatment with biologics. Disease activity, functional and social restrictions have decreased across all diseases. CONCLUSION: The improved health status of many patients with rheumatic diseases confirms the high level of care provided by the rheumatism centers involved in the NDB. The increasing specification of measuring instruments and the standardization of documentation systems are major challenges that the NDB will have to face in the coming years if it is to remain in the digital age.
31176839 Cerebral Trypanosomiasis in an Immunocompromised Patient: Case Report and Review of the Li 2019 Sep BACKGROUND: We document a case of central nervous system infection with Trypanosoma cruzi. CASE DESCRIPTION: An 88-year-old woman presented with altered mental status, right-sided weakness, and slurred speech. Her medical history was significant for methotrexate intake for rheumatoid arthritis, and she tested negative for human immunodeficiency virus. Magnetic resonance imaging of the brain showed bilateral thick and peripherally enhancing white matter lesions in the frontoparietal region with extensive surrounding vasogenic edema. A lumbar puncture revealed increased protein and lymphocytic pleocytosis, and needle biopsy highlighted brain necrosis, chronic inflammation, and numerous intracellular organisms suggestive of T. cruzi amastigotes. Despite treatment with benznidazole, the patient expired soon after presentation. CONCLUSION: Chagas disease should be included in the differential diagnosis of an immunocompromised patient presenting with a central nervous system mass, meningoencephalitis, or focal neurologic signs.
30327328 How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a 2019 Jan OBJECTIVES: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication. METHODS: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS. RESULTS: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95%  CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1  year of follow-up. CONCLUSIONS: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.
31257348 Clinical management for other iatrogenic immunodeficiency-associated lymphoproliferative d 2019 Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD), a category of immunodeficiency-associated LPD according to the World Health Organization classification, is associated with immunosuppressive drugs (ISDs). Several factors, including autoimmune disease (AID) activity, Epstein-Barr virus (EBV) infection, ISD usage, and aging, influence the development of OIIA-LPD, resulting in complicated clinical courses and outcomes. Most OIIA-LPD develops in patients with rheumatoid arthritis using methotrexate (MTX-LPD). The management of MTX-LPD is based on the clinical course, i.e., with/without regression, with/without relapse/regrowth event (RRE), LPD subtype, and ISDs for AIDs after LPD development. There are three clinical courses after ISD withdrawal: regressive LPD without relapse/regrowth (R-G), regressive LPD with RRE (R/R-G), and persistent LPD (P-G). The majority of EBV+ diffuse large B-cell lymphomas are classified in R-G, whereas classic Hodgkin lymphoma is generally classified in R/R-G. Polymorphic LPD (P-LPD) in MTX-LPD develops with heterogeneous pathological features similar to monomorphic LPD. Chemotherapy for MTX-LPD is selected according to that for de novo LPD, although the strategy for aggressive P-LPD and non-specific LPD is not well established. The absolute lymphocyte count in the peripheral blood has been suggested as a candidate marker for MTX-LPD development and RRE. Several clinical issues, including correct diagnosis among overlapping clinicopathological features in MTX-LPD and clinical management of LPD by ISDs other than MTX, require further investigation.
30853590 Cardiac Methotrexate-Induced Lymphoproliferative Disorder. 2019 Sep Methotrexate has been reported as an immunosuppressive agent associated with lymphoproliferative disorders. This report describes the case of a cardiac methotrexate-induced lymphoproliferative disorder that could be differentiated from a sinus of Valsalva aneurysm rupture by cardiac magnetic resonance imaging and fluorine-18 ((18)F)-fluorodeoxyglucose positron emission tomography combined with computed tomography. The definitive diagnosis was made by a tissue biopsy that was concomitantly performed with sinus of Valsalva aneurysm repair. Significant regression was seen in response to methotrexate withdrawal. To the best of our knowledge, this is the first case of a cardiac methotrexate-induced lymphoproliferative disorder.
31237785 Real-world utilization of methotrexate or prednisone co-therapy with etanercept among Cana 2019 Nov Objective: To evaluate whether initiation of etanercept therapy among patients with rheumatoid arthritis (RA) impacts use of co-therapy with methotrexate or prednisone, and to describe etanercept dosing dynamics compared to product monograph in the Canadian real-world setting. Methods: A retrospective cohort study was conducted using claims-level data from IQVIA Private Drug Plan database, Ontario Public Drug Plan database and Régie de l'assurance maladie du Québec database. Bio-naïve RA patients initiating etanercept between July 2014 and June 2015 were identified and their claims for methotrexate or prednisone were analyzed. Utilization of methotrexate or prednisone was calculated as average weekly dose in milligrams, and compared in the 6 months pre-initiation versus 12 months post-initiation of etanercept. Weekly etanercept dosing of each patient was calculated and analyzed to determine whether patients had at least 20% higher or lower average dose than monograph recommended dose (50 mg/week), and were then flagged as above-monograph or below-monograph, respectively. Results: A total of 2876 patients with RA (66% female, 76% aged 18-65) were included; 62% (n = 1,140) used methotrexate and 27% used prednisone (n = 498) both pre- and post-initiation of etanercept. In methotrexate patients, the average weekly dose dispensed was 25.4 mg in the 6 months pre-etanercept, and 25.0 mg in the 12 months post-etanercept initiation (p = .5282). In prednisone patients, the average weekly dose dispensed reduced from 122.6 mg pre-etanercept to 107.1 mg post-etanercept initiation (p = .2173). Among patients who were already on methotrexate or prednisone, after initiating on etanercept 16% (n = 213) and 34% (n = 254) of patients stopped methotrexate and prednisone, respectively. When compared to the recommended dose, 12% (n = 168) of patients were below-monograph and 7.1% of patients were above-monograph during their first year of etanercept therapy. Average etanercept dosing was consistently lower than product monograph during the follow-up year. Conclusions: Patients had a modest but not statistically significant decrease in prescribed doses of co-therapy with methotrexate and prednisone when etanercept was added to patients' therapy. In addition, 12-14% of patients stopped their co-therapy with methotrexate or prednisone. Further study is needed to understand the impact on patient outcomes and safety.
30092680 The three-year efficacy of iguratimod in clinical daily practice in patients with rheumato 2019 Sep Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.
30953327 Cardiovascular Disease Risk in Older Adults and Elderly Patients with Rheumatoid Arthritis 2019 Jun The prevalence of rheumatoid arthritis (RA), the most common autoimmune inflammatory arthritis, is increasing, partly due to the aging of the general population. RA is an independent risk factor for the development of cardiovascular disease (CVD). Older adults and elderly patients with RA develop CVD at a younger age compared with their general population peers. Both the traditional cardiovascular risk factors (age, sex, smoking, diabetes mellitus, hypertension), and systemic inflammation (i.e. high disease activity) are contributors to accelerated CVD in people with RA. Of the disease-modifying antirheumatic drugs (DMARDs) used for RA treatment, methotrexate, triple combination oral therapy (methotrexate, sulfasalazine, and hydroxychloroquine), tumor necrosis factor inhibitor biologicals, and abatacept have the strongest data in favor of the reduction of cardiovascular events in patients with RA. A treat-to-target strategy should be employed in older adults and elderly patients with RA to ensure appropriate reduction in cardiovascular risk, which can also prevent short- and long-term musculoskeletal disability. Our review findings are in line with the 2016 European League Against Rheumatism guideline recommendations, specifically: (1) RA disease activity should be controlled with an optimal DMARD regimen using a treat-to-target approach; (2) the lipid profile should be assessed and monitored in every older adult and elderly RA patient; (3) CVD risk factors, including smoking cessation, blood pressure, and blood glucose control, should be optimized; (4) RA treatment should be initiated as soon as possible; and (5) shared decision making regarding the treatment of patients with RA should include a discussion on the potential amelioration of increased cardiovascular risk.
30243781 Adverse consequences of low-dose methotrexate medication errors: data from French poison c 2019 May OBJECTIVE: The objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome. METHODS: Data on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes. RESULTS: Seventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5-22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg). CONCLUSIONS: This study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency.
31770193 A novel etanercept biosimilar Anbainuo plus methotrexate exhibits increased cost-effective 2019 Nov The aim of this study was to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) (ABN + MTX) versus conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients.Forty-eight moderate to severe RA patients underwent ABN + MTX or cDMARDs treatment were consecutively enrolled and assigned to ABN + MTX group (n = 26) and control group (n = 22). Patients were followed up and their disease activity and quality of life (QoL) were evaluated at 3rd month, 6th month and 12th month after initiation of treatment. Treatment costs of 2 groups were calculated, then pharmacoeconomic analysis was performed.ABN + MTX increased drug cost and total cost while decreased indirect cost compared with cDMARDs after 12-month treatment. ABN + MTX group gained additional 0.22 quality-adjusted life years (QALY) and yielded an incremental cost-effectiveness ratio (ICER) of ¥104,293.6 per QALY after treatment. Sensitivity analysis reveals that rising ABN price by 20% produced an ICER of ¥130,403.6 per QALY, which was still lower than 3 times of the mean gross domestic product (GDP) per capita during the same period in China (¥165,960). Besides, ABN + MTX was more cost-effective in severe RA patients compared to moderate RA patients.ABN + MTX is cost-effective in treating moderate to severe RA patients compared with cDMARDs, although the total cost of ABN + MTX is relatively higher.
30583708 Association of C35T polymorphism in dihydrofolate reductase gene with toxicity of methotre 2019 Mar BACKGROUND: Methotrexate (MTX), a folate analogue, is the most commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). However, high interindividual differences in drug response are present among RA patients. RESEARCH DESIGN AND METHODS: In a group of 234 RA patients treated with MTX, we investigated whether rs1650697 polymorphism in DHFR gene may have an impact on MTX efficacy and/or adverse drug effects (ADEs). Relative DAS28 values (rDAS28) were used for the estimation of MTX therapy and all ADEs were recorded. Patients were genotyped for selected polymorphism by real-time PCR method. RESULTS: According to the European League Against Rheumatism criteria after 6 months of MTX therapy, 196 patients (83.8%) were classified as responders (25 (10.7%) were good and 171 (73.1%) were moderate) and 38 patients (16.2%) as nonresponders. ADEs were observed in 55 patients (23.5%). CONCLUSIONS: Our results showed that the presence of T allele might be protective against MTX hepatotoxicity measured by transaminase levels (p = 0.05). Furthermore, among patients who also received low-dose corticosteroids, we have found a lower rDAS value in patients with CC genotype (p = 0.039).