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ID PMID Title PublicationDate abstract
24443001 An extra dose of rituximab improves clinical response in rheumatoid arthritis patients wit 2015 Jun OBJECTIVES: Since clinical non-response to 2×1000 mg rituximab has previously been found to be associated with incomplete B cell depletion, we determined, in a randomised controlled proof of concept study, whether patients with initial incomplete B cell depletion would benefit from an additional infusion of rituximab at week 4. METHODS: Patients with active rheumatoid arthritis despite methotrexate received a first infusion of rituximab 1000 mg and were tested for persistent B cells using highly sensitive flow cytometry on day 15. All received a second infusion of 1 g (according to license), but patients with persistent B cells were subsequently randomised double-blind to receive, 2 weeks later, either a third infusion of 1000 mg rituximab or placebo. Clinical response was determined by European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) criteria. RESULTS: Baseline characteristics were balanced between groups. Treatment with 3×1000 mg rituximab resulted in significantly greater depletion (lower B cell and plasmablast numbers between 8 and 28 weeks) paralleled by significantly better EULAR and ACR20 response rates at 40 weeks (p=0.035 and p=0.027, respectively) and 52 weeks (p=0.021 and p=0.043, respectively) compared with 2×1000 mg. Immunoglobulin titres remained stable in both arms, and adverse event rates were balanced. CONCLUSIONS: In rituximab-treated patients with incomplete B cell depletion (predictive of poor response), an extra 1000 mg infusion of rituximab at 4 weeks produced both better depletion and clinical responses than placebo with no worsening of safety. Degree of depletion is an important, but modifiable, determinant of response.
25007956 Five-year outcome in immune-mediated scleritis. 2014 Sep BACKGROUND: Immune-mediated scleritis is a rare condition, and the information on the clinical course and complications is scarce. The aim of this study was to identify prognostic factors, complications, and therapeutic effects in patients with immune-mediated scleritis. METHODS: Patients with diagnosis of scleritis and a follow-up time of 5 years were identified. Systemic disease, laboratory investigations, type of scleritis, disease activity, therapy, and complications were recorded. The study design was a retrospective, non-comparative, interventional case series. RESULTS: Systemic disease was identified in 15 (37%) patients at presentation and in 18 (45%) after 5 years. Rheumatoid arthritis (15%), granulomatosis with polyangiitis (7.5%), and polychondritis (7.5%) were the most predominant disorders. Persistent scleritis (>5 years) was associated with systemic disease (66 vs. 6%; p < 0.05) and positive auto-antibodies (48 vs. 23%; p = 0.18). Control of ocular inflammation was achieved in 38 of 40 (95%). Prednisone (14 patients) and/or methotrexate (8) were the predominant drugs to control persistent disease. Complications included interstitial keratitis (2), inflammatory astigmatism (2), corneal melt (3), macular edema (6), and severe systemic disease (5). CONCLUSION: The presence of systemic disease and positive auto-antibodies are associated with persistent scleritis. Immunosuppressive agents allow control of scleritis, but may contribute to severe systemic complications.
25420554 Combination therapy for early rheumatoid arthritis: a treatment holiday perspective. 2015 Jan To date, the significance of early intervention with methotrexate and biological disease-modifying anti-rheumatic drugs for rheumatoid arthritis (RA) has not been realized. Longitudinal safety and cost have arisen as new concerns. The concept of a treatment holiday, drug discontinuation after achieving remission, may solve these problems. The authors performed a systematic literature review and identified 13 reports from 10 studies (TNF20, BeSt, OPITMA, HIT-HARD, IMPROVED, PRIZE, IDEA, EMPIRE, tREACH and AVERT) for early RA (≤2 years). Eight out of 13 reports (61.5%) were published in 2013 or 2014, indicating emerging interest in recent years. Also, the authors performed a sub-analysis of the HONOR study (n = 51) to compare early (≤2 years) and established RA. The proportions of remission (REM) and low disease activity were higher in early RA (REM: 63.0 vs 33.3%, p = 0.0346; low disease activity: 77.8 vs 45.8%, p = 0.0185). In conclusion, early intervention is beneficial for successful treatment holiday, which may lead to risk and cost reduction. However, further investigation is required.
24854959 Tocilizumab in the treatment of rheumatoid arthritis: a cost-effectiveness analysis in the 2014 Aug BACKGROUND: Since receiving a positive recommendation in England, Wales and Scotland, tocilizumab (TCZ) is one of the options available to clinicians for the treatment of rheumatoid arthritis (RA) patients in the UK. OBJECTIVE: The objective of this study was to evaluate the cost effectiveness of adding TCZ to the current treatment sequence of RA patients from a UK payer's perspective over a patient lifetime horizon. METHODS: An individual sampling model was developed to synthesise all clinical and economic inputs. Two scenarios were explored separately: patients contraindicated to methotrexate (MTX) and those MTX tolerant. For each scenario, the analysis compared three strategies. The standard of care (SoC) strategy included a sequence of the most commonly prescribed biologics; the other two comparator strategies considered the addition of TCZ to SoC at first line and second line. Patient characteristics were representative of UK patients. Treatment efficacy and quality-of-life evidence were synthesised from clinical trials and secondary sources. An analysis of a patient registry informed the model parameters regarding treatment discontinuation. The safety profile of all treatments in a given strategy was based on a network meta-analysis and literature review. Resource utilisation, treatment acquisition, administration, monitoring and adverse event treatment costs were considered. All costs reflect 2012 prices. Uncertainty in model parameters was explored by one-way and probabilistic sensitivity analysis. RESULTS: In the MTX-contraindicated population, if TCZ was added to the SoC in first line, the estimated incremental cost-effectiveness ratio (ICER) was £7,300 per quality-adjusted life-year (QALY) gained; if added in second line, the estimated ICER was £11,400 per QALY. In the MTX-tolerant population, the estimated costs and QALYs of the TCZ strategy were similar to those of the SoC strategy. Sensitivity analysis showed that parameters that affect the treatment cost (such as patient weight) can have a noticeable impact on the overall cost-effectiveness results. The majority of the other sensitivity analyses resulted in modest changes to the ICER. CONCLUSION: For the treatment of RA in MTX-tolerant and contraindicated patients, the addition of TCZ to the SoC was estimated to be a cost-effective strategy.
23991717 Etanercept in the treatment of rheumatoid arthritis. 2013 Oct INTRODUCTION: Biologic agents have transformed clinical outcomes in rheumatoid arthritis, and there are now several immune-modulating therapies available. Tumour necrosis factor-α (TNF-α) inhibitors were the first biologic drug class licensed for the treatment of rheumatoid arthritis. Etanercept is a fusion protein composed of two TNF receptors bound to the constant portion (Fc) of human immunoglobulin G (IgG). AREAS COVERED: This article will consider the pharmacological properties of etanercept and the clinical efficacy data presented in clinical trials. Its safety in clinical practice will be reviewed. EXPERT OPINION: There is overwhelming evidence to support the use of etanercept in rheumatoid arthritis. Trial data demonstrate etanercept's efficacy in reducing structural damage, improving clinical outcomes and inducing remission. Optimal response to therapy is seen when used in combination with methotrexate and when initiated early. Etanercept is an attractive therapeutic option given the excellent safety profile, reduced immunogenicity and ease of administration.
23885678 Cardiovascular risk in rheumatoid arthritis: comparing TNF-α blockade with nonbiologic DM 2013 Aug BACKGROUND: Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD). METHODS: Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months. RESULTS: We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075). CONCLUSION: Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.
24413827 A unique case of phaeohyphomycosis subretinal abscess in a patient with arthropathy and lu 2013 Dec A 67-year-old former gold miner with rheumatoid arthritis, treated with steroids and methotrexate, presented to eye casualty with a painful right eye. Examination revealed an anterior uveitis and despite an initial response to topical steroids, the intraocular inflammation worsened with anterior and posterior uveitis development. Re-examination showed a white mass in the peripheral nasal retina initially suspected of being active Toxoplasmosis infection and anti-toxoplasmosis treatment commenced. After improvement and tapering of this treatment, the intraocular inflammation reoccurred. Cytopathological examination of a pars plana vitrectomy obtained vitreous sample that showed a non-diagnostic non-infectious chronic vitritis. The vitreoretinal surgeons elected to do a direct biopsy of the white subretinal mass in the peripheral nasal area. This revealed, quite unexpectedly, an abscess containing pigmented phaeohyphomycosis fungi. This case report documents the multidisciplinary approach that assisted in clinching a final diagnosis and the role of sub-retinal biopsy in this unprecedented scenario.
24798341 1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model o 2014 Sep Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with no known cure. Current strategies to treat RA, including methotrexate (MTX), target the later inflammatory stage of disease. Recently, we showed that inhibiting indoleamine-2,3-dioxygenase (IDO) with 1-methyl-tryptophan (1MT) targets autoantibodies and cytokines that drive the initiation of the autoimmune response. Therefore, we hypothesized that combining 1MT with MTX would target both the initiation and chronic inflammatory phases of the autoimmune response and be an effective co-therapeutic strategy for arthritis. To test this, we used K/BxN mice, a pre-clinical model of arthritis that develops joint-specific inflammation with many characteristics of human RA. Mice were treated with 1MT, MTX, alone or in combination, and followed for arthritis, autoantibodies, and inflammatory cytokines. Both 1MT and MTX were able to partially inhibit arthritis when used individually; however, combining MTX + 1MT was significantly more effective than either treatment alone at delaying the onset and alleviating the severity of joint inflammation. We went on to show that combination of MTX + 1MT did not lower inflammatory cytokine or autoantibody levels, nor could the synergistic co-therapeutic effect be reversed by the adenosine receptor antagonist theophylline or be mimicked by inhibition of polyamine synthesis. However, supplementation with folinic acid did reverse the synergistic co-therapeutic effect, demonstrating that, in the K/BxN model, MTX synergizes with 1MT by blocking folate metabolism. These data suggest that pharmacological inhibition of IDO with 1MT is a potential candidate for use in combination with MTX to increase its efficacy in the treatment of RA.
22763757 Association of the TYMS 3G/3G genotype with poor response and GGH 354GG genotype with the 2013 Mar PURPOSE: Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs). METHODS: The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G > T and 452 C > T), CCND1 (870 A > G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX. RESULTS: According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as non-responders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p = 0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p = 0.003). No other significant association were observed. CONCLUSION: The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T > G polymorphism may have high predictive value for myelosuppression in RA patients.
24145554 TNF-α gene silencing using polymerized siRNA/thiolated glycol chitosan nanoparticles for 2014 Feb Among various proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA), tumor necrosis factor (TNF)-α plays a pivotal role in the release of other cytokines and induction of chronic inflammation. Even though siRNA has the therapeutic potential, they have a challenge to be delivered into the target cells because of their poor stability in physiological fluids. Herein, we design a nanocomplex of polymerized siRNA (poly-siRNA) targeting TNF-α with thiolated glycol chitosan (tGC) polymers for the treatment of RA. Poly-siRNA is prepared through self-polymerization of thiol groups at the 5' end of sense and antisense strand of siRNA and encapsulated into tGC polymers, resulting in poly-siRNA-tGC nanoparticles (psi-tGC-NPs) with an average diameter of 370 nm. In the macrophage culture system, psi-tGC-NPs exhibit rapid cellular uptake and excellent in vitro TNF-α gene silencing efficacy. Importantly, psi-tGC-NPs show the high accumulation at the arthritic joint sites in collagen-induced arthritis (CIA) mice. Treatment monitoring data obtained by the matrix metalloproteinase 3-specific nanoprobe and microcomputed tomography show that intravenous injection of psi-tGC-NPs significantly inhibits inflammation and bone erosion in CIA mice, comparable to methotrexate (5 mg/kg). Therefore, the availability of psi-tGC-NP therapy that target specific cytokines may herald new era in the treatment of RA.
23918035 Biologic and oral disease-modifying antirheumatic drug monotherapy in rheumatoid arthritis 2013 Dec Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
23343013 Old drugs, old problems: where do we stand in prediction of rheumatoid arthritis responsiv 2013 Jan 23 Methotrexate (MTX) is the central drug in the management of rheumatoid arthritis (RA) and other immune mediated inflammatory diseases. It is widely used either in monotherapy or in association with other synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs). Although comprehensive clinical experience exists for MTX and synthetic DMARDs, to date it has not been possible to preview correctly whether or not a patient will respond to treatment with these drugs. Predicting response to MTX and other DMARDs would allow the selection of patients based on their likelihood of response, thus enabling individualized therapy and avoiding unnecessary adverse effects and elevated costs. However, studies analyzing this issue have struggled to obtain consistent, replicable results and no factor has yet been recognized to individually distinguish responders from nonresponders at treatment start. Variables possibly influencing drug effectiveness may be disease-, patient- or treatment-related, clinical or biological (genetic and nongenetic). In this review we summarize current evidence on predictors of response to MTX and other synthetic DMARDs, discuss possible causes for the heterogeneity observed and address its translation into daily clinical practice.
24022747 M-ficolin levels reflect disease activity and predict remission in early rheumatoid arthri 2013 Dec OBJECTIVE: To assess plasma M-ficolin concentrations in disease-modifying antirheumatic drug (DMARD)-naive patients with early rheumatoid arthritis (RA), to investigate the correlation of M-ficolin concentrations with disease activity markers, and to determine the predictive value of M-ficolin with respect to the Disease Activity Score in 28 joints (DAS28). METHODS: The study group included 180 DMARD-naive patients with early RA who participated in a randomized controlled trial of methotrexate and intraarticular glucocorticoids plus either adalimumab or placebo/adalimumab. One hundred healthy control subjects and 51 patients with chronic RA were also assessed. A sandwich-type time-resolved fluorometric immunoassay was used for quantification of plasma M-ficolin. RESULTS: At baseline, M-ficolin levels were highest in the group of DMARD-naive patients with newly diagnosed active RA, and the level in these patients decreased 26% after 1 year of aggressive treatment. The baseline M-ficolin level correlated with 5 of 7 disease activity markers, including the DAS28 and the Health Assessment Questionnaire (HAQ), and a similar pattern of correlations was observed at 1 year. Multiple logistic regression analysis showed that an elevated M-ficolin level at baseline was the strongest predictor of not achieving either DAS28 remission (odds ratio [OR] 4.18, 95% confidence interval [95% CI] 2.02-8.63) or low disease activity (OR 2.45, 95% CI 1.13-5.28) at 1 year. The presence of a baseline M-ficolin level in the lowest quartile resulted in sensitivity of 29%, specificity of 93%, and positive predictive value of 95% for low disease activity at 1 year. CONCLUSION: In patients with early RA, elevated plasma M-ficolin levels correlated with a high DAS28 and a high HAQ score at baseline and 1 year. A low M-ficolin level was the strongest predictor of remission and low disease activity in a multivariate analysis.
24786931 The effect of intravenous golimumab on health-related quality of life in rheumatoid arthri 2014 Jun OBJECTIVE: To evaluate the effects of intravenous (IV) golimumab 2 mg/kg + methotrexate (MTX) on patient-reported measures of health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA) despite prior MTX therapy. METHODS: In this randomized, multicenter, double-blind, placebo-controlled, phase III trial, adults with RA were randomly assigned to receive IV placebo (n = 197) or golimumab 2 mg/kg (n = 395) infusions at Week 0, Week 4, and every 8 weeks thereafter. All patients continued stable oral MTX (15-25 mg/wk). HRQOL assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI; physical function), Medical Outcomes Study Short Form-36 questionnaire physical/mental component summary (SF-36 PCS/MCS) scores, EQ-5D assessment of current health state, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, and disease effect on productivity [10-cm visual analog scale (VAS)]. RESULTS: Mean HAQ-DI improvements from baseline were significantly greater with golimumab + MTX than placebo + MTX at Week 14 and Week 24 (p < 0.001). Significantly greater improvements in all 8 individual SF-36 subscores and both the SF-36 PCS and MCS scores (p < 0.001) also accompanied golimumab + MTX therapy. Improved EQ-5D and EQ-5D VAS (p < 0.001) and FACIT-Fatigue (p < 0.001) scores were also observed for golimumab + MTX-treated patients at Week 12, Week 16, and Week 24, and greater proportions of golimumab + MTX-treated patients had clinically meaningful improvements in these measures. Greater reductions in disease effect on productivity were observed with golimumab + MTX versus placebo + MTX at Week 24 (p < 0.001). Improvements in physical function, HRQOL, fatigue, and productivity significantly correlated with disease activity improvement. CONCLUSION: In active RA, IV golimumab + MTX significantly improved physical function, HRQOL, fatigue, and productivity using multiple measurement tools; all correlated with improvements in disease activity (NCT00973479, EudraCT 2008-006064-11).
25322199 Methotrexate: a gold standard for treatment of rheumatoid arthritis. 2014 Dec Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.
24123677 A novel disease-modifying antirheumatic drug, iguratimod, ameliorates murine arthritis by 2013 Nov 15 Iguratimod, a novel disease-modifying antirheumatic drug, which is now used in clinics in China and Japan, has been confirmed as a highly efficacious and safe drug for rheumatoid arthritis therapy. The antiarthritic mechanism of iguratimod, especially compared with that of the classical disease-modifying antirheumatic drugs, has not been elucidated. In this study, we conducted a comparative analysis of the antiarthritic effects of iguratimod and two reference drugs, methotrexate and leflunomide. We found that iguratimod dose dependently and potently inhibited arthritic inflammation of the synovium in collagen-induced arthritis and predominantly targeted IL-17 signaling. Consistent with its effects in vivo, iguratimod significantly suppressed the expression of various proinflammatory factors triggered by IL-17 in the cultured fibroblast-like synoviocytes. The inhibition of IL-17 signaling by iguratimod was further linked to a decrease in the mRNA stability of related genes and a reduction in phosphorylation of MAPKs. Iguratimod mainly targets Act1 to disrupt the interaction between Act1 and TRAF5 and IKKi in the IL-17 pathway of synoviocytes. Together, our results suggest that iguratimod yields a strong improvement in arthritis via its unique suppression of IL-17 signaling in fibroblast-like synoviocytes. This feature of iguratimod is different from those of methotrexate and leflunomide. This study may be helpful for further understanding the unique antiarthritic mechanism of iguratimod in patients with rheumatoid arthritis.
23873875 Evaluation of myocardial function in patients with rheumatoid arthritis using strain imagi 2014 Oct OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD), although strategies to detect subclinical CVD are poorly characterised. The purpose of this study was to assess myocardial function by speckle-tracking echocardiography strain imaging in patients with RA without known CVD. METHODS: Eighty-seven patients with RA selected from a population-based sample underwent echocardiography. Left ventricular (LV) and right ventricular (RV) longitudinal peak systolic strain were measured. A subset of 59 patients with RA was compared with 59 age-, gender- and race-matched subjects with normal echocardiography and no CVD or risk factors. RESULTS: The mean ± SD age of the patients with RA and the normal patients was 55.7±12.1 and 54.5±12.2 years (p=0.42), respectively, with 45 (76%) women in each group. Global LV strain (-15.7±3.2% vs -18.1±2.4%, p<0.001) and RV strain (-17.9±4.7% vs -20.7±2.4%, p<0.001) was reduced in patients with RA compared with normal patients. Among all 87 patients with RA the mean disease duration and C-reactive protein at echocardiography were 10.0±6.1 years and 3.5±3.7 mg/L, and 74% were seropositive. Adjusted univariate regression analysis demonstrated a significant correlation between global LV strain and RA Health Assessment Questionnaire disability index (p=0.032), and borderline associations with prior use of oral corticosteroids (p=0.062) and methotrexate (p=0.054) after adjustment for age, gender, blood pressure, body mass index, heart rate and LV mass index. CONCLUSIONS: Global longitudinal LV and RV strain is reduced in patients with RA compared with healthy patients. Strain abnormalities correlate with RA disease severity. Strain imaging by echocardiography may detect early myocardial dysfunction in RA.
25274891 Coronary and abdominal aorta calcification in rheumatoid arthritis: relationships with tra 2014 Nov OBJECTIVE: To assess the influence of traditional cardiovascular (CV) risk factors, disease characteristics, and concomitant treatments in patients with rheumatoid arthritis (RA) on coronary artery calcification (CAC) and abdominal aorta calcification (AAC). METHODS: In our cross-sectional study, 75 patients with RA were compared with 75 age-matched and sex-matched control participants. The CAC and AAC scores were measured by computed tomography in patients with no clinical evidence of coronary artery disease. The relationships between the presence or absence of CAC and AAC and traditional CV risk factors, disease characteristics, and concomitant treatments in patients with RA were assessed in a multiple logistic regression analysis. RESULTS: The RA and control groups did not differ significantly in terms of age, sex composition, or the prevalence of traditional CV risk factors. AAC and CAC were more prevalent and severe in patients with RA than in controls. Older age (OR=1.15, p<0.01) and hypertension (OR=3.77, p=0.04) were found to be independently associated with CAC, whereas current use of methotrexate (MTX; OR=0.12, p=0.01) was found to be associated with the absence of CAC. Older age (OR per yr=1.17, p<0.001) and erosive arthritis (OR=3.78, p=0.03) were found to be independently associated with AAC. CONCLUSION: Our study demonstrates that in patients with RA, (1) CAC and AAC are more prevalent and more severe compared with age-matched and sex-matched control participants, (2) current use of MTX is a major determinant of the absence of CAC, and (3) erosive arthritis is a major determinant of AAC.
24682293 Assessment of the treat-to-target strategy in patients with refractory rheumatoid arthriti 2014 Oct AIM: The goal of the present study was to prospectively assess the long-term clinical outcome of biologic modifying drug therapy in a population of Saudi rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: This is the first prospective, long-term report on the efficacy and safety of biologic therapy in Saudi RA patients. It is a single center, observational study with a follow-up period of 3 years. Enrolled were 120 biologic naïve patients (94 women, 78.3 %; mean age 48.4 ± 17.9 years, mean disease duration 7.3 ± 3.9 years) with the diagnosis of RA (ACR/EULAR, 2010 criteria) who were inadequate responders to methotrexate and synthetic DMARDs. RESULTS: After 3 years, the mean Disease Activity Index-28 (DAS-28), Health Assessment Questionnaire (HAQ), Pain Score, ESR, and CRP values improved significantly. Of the 99 patients completing the 3-year follow-up, 35.3 % of patients achieved DAS-28 remission and 53.5 % achieved low disease activity, and 11.1 % of patients had moderate to high activity scores. At the 3-year follow-up, 80 % of patients had no evidence of significant radiographic progression (achieved < 0.5 of the mean total Sharp score). Infections were reported in 11.7 % and significantly correlated with conjugate use of oral prednisolone at doses above 5 mg/day, with chest infections being the most common type of infection (6.7 %). CONCLUSION: The results of this study can be understood as real-life clinical experience displaying the incremental benefit of biologic therapy in refractory disease when it is added to other optimal strategies. The study showed satisfying clinical and functional benefit with considerable safety.
23224330 Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated 2013 May OBJECTIVE: To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN. METHODS: Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.4. ALT was measured every three months. With logistic regression analyses, baseline variables predictive of first ALT of >2× ULN were identified and the association between use of concomitant antirheumatic drugs, the actual and cumulative dose of MTX and ALT of >2× ULN was determined. RESULTS: In total, 498 patients ever initiated MTX, with a total duration on MTX of 1,416 patient-years. In 89 patients, a first incidence of ALT of >2× ULN occurred. Incidence rate was 6.3 per 100 patient-years and cumulative incidence 18 %. ACPA positivity and baseline ALT of >1× ULN were independent predictors of later ALT of >2× ULN (OR 1.8 (95 % CI, 1.1-3.1) and OR 3.1 (95 % CI, 1.6-6.2), respectively). Smoking showed a trend (OR 1.6 (95 % CI, 0.98-2.7)). Mean MTX dosage over time was higher in patients with an ALT of >2× ULN. Patients who did not have an ALT of >2× ULN used more concomitant disease-modifying antirheumatic drugs and longer. CONCLUSIONS: In RA patients treated with MTX according to a dynamic strategy resembling daily clinical practice, incidence of increased ALT of >2× ULN was lower than previously reported, and also without treatment adjustments, persistence was rare. The recommendations for ALT monitoring may be reevaluated.