Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25190551 Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 2015 Apr In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.
25627219 [The prevalence of anemia in rheumatoid arthritis]. 2014 Jul OBJECTIVES: The aim of this study was to evaluate the prevalence of anaemia in rheumatoid arthritis (RA). PATIENTS AND METHODS: 89 patients who fulfilled American College of Rheumatology (ACR) criteria for RA were included in this study. The mean disease duration was 10.9±8.8 years. All patients received methotrexate (10.5±5.5 mg/week) in combination with folic acid. Steroid hormones were prescribed to 92% (19.3±3.8 mg/day) of patients. Erythrocyte sedimentation rate (ESR) and levels of hemoglobin, C-reactive protein (CRP), tumour necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) were evaluated in all patients. The World Health Organization (WHO) criteria for anaemia uses a hemoglobin threshold of <120 g/L for women and <130 g/L for men. RESULTS: Anaemia was observed in 57 (64%) of the patients (1st group), the other patients (2nd group) had normal levels of hemoglobin (135.5±10.7 g/L). Duration and activity of RA were significantly higher (p<0.05) in the 1st group compared with the 2nd. ESR, CRP, TNFα, and IL-1β mean levels were significantly increased (p<0.05) in the 1st group when compared with the 2nd group. Negative correlations between hemoglobin level and ESR, CRP, TNFα, and IL-1β concentrations were observed. CONCLUSION: This study showed for the first time in Ukraine that in 46% of patients with RA, anaemia was diagnosed. A reduction of hemoglobin level was associated with a high activity of disease.
24291654 Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocor 2015 Feb OBJECTIVES: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival. METHODS: Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking. RESULTS: During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28  > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97). CONCLUSIONS: Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.
23874006 Methotrexate in rheumatoid arthritis: a quarter century of development. 2013 Methotrexate (MTX) is now the most popular drug worldwide for the treatment of rheumatoid arthritis. Low-dose, weekly MTX (10 to 25 mg/wk) used as either monotherapy or in combination with other drugs has a superior efficacy profile as defined in placebo-controlled trials and comparable efficacy to other drugs including anti-TNF therapy. At 1 year, one third of patients on MTX have no radiographic progression and even greater effects are seen when combined with targeted biological therapies. MTX is well tolerated; gastrointestinal toxicity is the most common toxicity with rarely bone marrow, lung, or liver toxicity. MTX therapy has been a major advance in the treatment of rheumatoid arthritis and is now the cornerstone of therapy.
25726631 Rheumatoid arthritis and ischemic strokes in a young woman. Are these conditions interrela 2014 Oct Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which is associated with an increased risk of cardio and cerebrovascular pathology. A 48-year old Caucasian female was admitted for diffuse arthralgias. She was diagnosed eight years before with seropositive RA and she received Methotrexate, Prednisone and anti-inflammatory drugs. A week after the admission the patient presented sudden onset of left hemiplegia. Cerebral CT scan was suggestive for acute infarction in the right middle cerebral artery area and an old sequelar infarction in the left posterior artery area. Laboratory tests revealed: erythrocyte sedimentation rate of 40 mm/hour, fibrinogen 656 mg/dL, C-reactive protein of 20 mg/dL, rheumatoid factor 66.83 U/mL, anti CCP3 IgG 213.54 U/mL, ANA 128.126 U/mL. Also, she had high LDL-cholesterol serum concentration (190 mg/dL). The ECG revealed sinus rhythm, QRS axis-45 degrees, antero-lateral ischemia. Ultrasound examination of cervico-cerebral arteries emphasized occlusion of the left internal carotid artery, large atheromas in both carotid and vertebral arteries. A treatment with anti-aggregant and statin was started, and the former treatment for RA was continued with a raised Prednisone dose. The outcome was favorable, the patient's motor deficit improved (3/5 BMRC at the upper limb and 4/5 at the inferior limb) and she was able to walk with a cane support. She also presented an alleviation in the laboratory test status. Ischemic stroke is a possible complication of RA, presenting as principal risk factor precocious atherosclerosis. A better control of inflammation by new anti-rheumatic treatments will protect the RA patients of deleterious effects of ischemic stroke.
23709375 Evaluation of selected bone metabolism markers in rheumatoid arthritis patients. 2013 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic disease of connective tissue characterized by progressive destructive arthritis associated with deformation and impairment of the function of the motor system. RA patients more often present secondary osteoporosis and increased risk of fractures. The aetiology of the process remains not fully understood. A significant role is played by proinflammatory cytokines being common mediators of both inflammatory processes and bone remodelling. OBJECTIVES: The purpose of the study was to evaluate the effect of activity of the inflammation and of applied therapy on osteogenesis marker concentrations in RA patients. MATERIAL AND METHODS: Thirty six female patients with RA, confirmed according to ACR criteria, aged from 35 to 77 years were qualified into the study. A control group included 45 healthy women aged between 34 and 78 years. Clinical evaluation (number of painful and swollen joints, DAS 28) and evaluation of RA laboratory activity (ESR, CRP, blood cell count) and levels of selected bone metabolism markers (osteocalcin, PICP) and serum interleukin 1 levels were performed to carry out the study. X-rays of hands and densitometric scanning of the femoral bone neck and spine were completed in order to assess the advancement of lesions in the bones. RESULTS: Osteocalcin and PICP levels were significantly lower in the RA groups compared to the control group (2.51 ± 0.22 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001; 0.292 ± 0.047 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001 respectively). A statistically significant difference was also observed between the levels of osteocalcin and PICP in both sub-groups of RA patients (DAS28 ≤ 5.1 and DAS28 > 5.1) and the control (osteocalcin 2.48 ± 0.23 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001; 2.52 ± 0.22 pg/mL vs. 18.65 ± 12.84 pg/mL, p < 0.0001 respectively and PICP 0.281 ± 0.053 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001; 0.298 ± 0.044 pg/mL vs. 0.829 ± 0.263 pg/mL, p < 0.0001 respectively). No correlation was demonstrated between the levels of selected bone metabolism markers and the therapy with methotrexate or cyclosporine. CONCLUSIONS: Analysis of the obtained results confirms the presence of disorders of bone metabolism in RA patients. A chronic inflammatory process favors the development of osteoporosis in RA patients. Reduced levels of bone metabolism markers (osteocalcin, PICP) in the study group, compared to the control, may indicate a reduced pace of osteogenesis in RA patients. No effect of therapy with methotrexate and cyclosporine on bone metabolism in that group of patients was found.
24728880 The impact of hepatitis screening on diagnosis and treatment in rheumatoid arthritis. 2014 Dec Identification of patients with exposure to viral hepatitis is an important part of the care of patients with inflammatory arthritis. This study was conducted to assess the extent of hepatitis B and C screening, and the prevalence of viral hepatitis in a cohort of patients with established rheumatoid arthritis (RA). The medical records of 100 consecutive RA patients were retrospectively analysed for screening of hepatitis B surface antigen, surface antibody and core antibody and hepatitis C antibody. A teaching session was then conducted with the rheumatology team, emphasising the rationale for viral hepatitis testing. We then prospectively analysed 100 more RA patients to see if hepatitis screening improved. In the initial 100 patients (21 % male, mean age 65 years), 85 % were taking methotrexate and 22 % biologic treatments. A complete hepatitis screen was present in 8 %, while 12 % had hepatitis B core antibody checked and 53 % had been tested for hepatitis C.The second cohort of patients was similar to the first in terms of demographics and treatment. A complete hepatitis screen was available in 63 %, while 65 % had hepatitis B core antibody checked and 81 % had been tested for hepatitis C.In total, we identified 4 new cases of positive hepatitis B core antibody, 11 cases of positive hepatitis B surface antibody and 1 case of positive hepatitis C antibody. Even in populations where hepatitis B or C is non-endemic, screening will reveal new cases. Educational initiatives are helpful in teaching staff to screen patients.
25359382 Methotrexate in combination with other DMARDs is not superior to methotrexate alone for re 2015 Jan OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. RESULTS: Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). CONCLUSIONS: For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EUDRACT NUMBER: 2008-007225-39.
23974102 Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF 2013 Sep 15 The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. CD4+ T cells comprise a large proportion of the inflammatory cells that invade the synovial tissue and may therefore be a cell type of pathogenic importance. Both methotrexate and infliximab are effective in the treatment of inflammatory arthritis; however, the biological effects triggered by these treatments and the biochemical mechanisms underlining the cell response are still not fully understood. Thus, in this study the global metabolic changes associated with methotrexate or infliximab treatment of isolated human CD4+ T cells were examined using gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. In total 148 metabolites involved in selective pathways were found to be significantly altered. Overall, the changes observed are likely to reflect the effort of CD4+ cells to increase the production of cellular reducing power to offset the cellular stress exerted by treatment. Importantly, analysis of the global metabolic changes associated with MTX or infliximab treatment of isolated human CD4+ T cells suggested that the toxicity associated with these agents is minimal when used at clinically relevant concentrations.
25036563 Pigmented villonodular synovitis developing in a patient with rheumatoid arthritis. 2014 Aug A 56-year-old man developed pigmented villonodular synovitis (PVNS) 3 years after he was diagnosed with rheumatoid arthritis (RA). He had been successfully treated with methotrexate, leflunomide, sulfadiazine, and intra-articular knee injection of etanercept (tumor necrosis factor α inhibitor) in 2010. He stopped all drugs for arthritis 1 year later for disease remission. He was readmitted for right knee pain and swelling in 2013, when the magnetic resonance imaging and arthroscopy of the right knee indicated PVNS. Following surgical resection, the patient was doing well after 1 year. This rare case is the first reported case in English-language literature of PVNS of the knee seen in RA patients and illustrates the importance of differential diagnosis of this condition with synovial cysts, which are commonly found in RA.
24523570 Predictive factors of response to biological disease modifying antirheumatic drugs: toward 2014 Many therapies are now available for patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate including tumor necrosis factor inhibitors, abatacept, tocilizumab, and rituximab. Clinical response to drugs varies widely between individuals. A part of this variability is due to the characteristics of the patient such as age, gender, concomitant therapies, body mass index, or smoking status. Clinical response also depends on disease characteristics including disease activity and severity and presence of autoantibodies. Genetic background, cytokine levels, and immune cell phenotypes could also influence biological therapy response. This review summarizes the impact of all those parameters on response to biological therapies.
24284432 Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid ar 2014   Methotrexate (MTX) is a derivative of folic acid (folate) and commonly used as an anchor drug for the treatment of rheumatoid arthritis (RA). The pharmacokinetics (PK) and pharmacodynamics (PD) of MTX entirely depends on the function of specific transporters that belong to the two major superfamilies, solute carrier transporters and ATP-binding cassette transporters. Several transporters have been identified as being able to mediate the transport of MTX, and suggested to be involved in the disposition in the body and in the regulation of intracellular metabolism in target cells, together with several enzymes involved in folate metabolism. Thus, drug-drug interactions through the transporters and their genetic polymorphisms may alter the PK and PD of MTX, resulting in an interpatient variability of efficacy. This review summarizes the PK and PD of MTX, particularly in relation to RA therapy and focuses on the roles of transporters involved in PK and PD with the aim of facilitating an understanding of the molecular basis of the mechanism of MTX action to achieve its effective use in RA therapy.
24473673 Clinical, radiographic and immunogenic effects after 1 year of tocilizumab-based treatment 2014 May OBJECTIVE: To assess the 1-year efficacy and safety of a regimen of tocilizumab plus methotrexate or placebo, which was augmented by a treat-to-target strategy from week 24. METHODS: ACT-RAY was a double-blind, 3-year trial. Adults with active rheumatoid arthritis despite methotrexate were randomised to add tocilizumab to ongoing methotrexate (add-on strategy) or to switch to tocilizumab plus placebo (switch strategy). Tocilizumab 8 mg/kg was administered every 4 weeks. Conventional open-label disease-modifying antirheumatic drugs (DMARDs) other than methotrexate were added at week 24 or later in patients with DAS28>3.2. RESULTS: 556 patients were randomised; 85% completed 52 weeks. The proportion of patients receiving open-label DMARDs was comparable in the add-on (29%) and switch (33%) arms. Overall, week 24 results were maintained or further improved at week 52 in both arms. Some endpoints favoured the add-on strategy. Mean changes in Genant-modified Sharp scores were small; more add-on (92.8%) than switch patients (86.1%) had no radiographic progression. At week 52, comparable numbers of patients had antidrug antibodies (ADAs; 1.5% and 2.2% of add-on and switch patients, respectively) and neutralising ADAs (0.7% and 1.8%). Rates of serious adverse events and serious infections per 100 patient-year (PY) were 11.3 and 4.5 in add-on and 16.8 and 5.5 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3× upper limit of normal were observed in 11% of add-on and 3% of switch patients. CONCLUSIONS: Despite a trend favouring the add-on strategy, these data suggest that both tocilizumab add-on and switch strategies led to meaningful clinical and radiographic responses.
23724971 Vaccination against seasonal influenza is effective in Japanese patients with rheumatoid a 2013 OBJECTIVE: To investigate the effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA) from a large practice-based cohort. METHOD: Patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort completed self-administered questionnaires as part of the April IORRA surveys of 2001, 2002, 2003, and 2007, which included their influenza vaccination status and occurrence of an actual influenza attack. Vaccine coverage rate and attack rates were calculated in each season. Relative risks (RRs) of vaccination for an actual influenza attack were evaluated and risk factors for influenza infection were determined by multiple logistic regression analysis. RESULTS: Data from 3529, 4518, 4816, and 4872 patients in the 2000/01, 2001/02, 2002/03, and 2006/07 seasons, respectively, were analysed. Coverage rates were increased from 12.2% in the 2000/01 season to 38.7% in the 2006/07 season. For each season, the attack rates in vaccinated patients trended lower than the rates in unvaccinated patients but the differences were not significant; however, by combining these four seasonal results, the attack rate was significantly lower for vaccinated patients [RR 0.83, 95% confidence interval (CI) 0.71-0.95, p < 0.01]. Male gender [odds ratio (OR) 1.48, 95% CI 1.25-1.76, p < 0.001] was associated with increased risk whereas vaccination was associated with reduced risk for influenza attack (OR 0.76, 95% CI 0.63-0.91, p < 0.01). There were no associations between influenza attacks and RA disease activity, treatment with methotrexate (MTX) or corticosteroids. CONCLUSION: Influenza vaccination was effective in patients with RA regardless of disease activity or treatment.
23861303 Golimumab, a human anti–tumor necrosis factor monoclonal antibody, injected subcutaneous 2013 Nov OBJECTIVE: To assess 2-year golimumab efficacy/safety in patients with active rheumatoid arthritis (RA) who had never taken methotrexate (MTX). METHODS: RA patients who had never taken MTX (n = 637) were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4) every 4 weeks. Nonresponders based on week 28 swollen/tender joint counts changed treatment as follows: group 1 added golimumab 50 mg, group 2 added MTX, group 3 increased golimumab to 100 mg, and group 4 had no change. Most group 1 patients (85%) initiated golimumab 50 mg + MTX at week 28 or subsequently at week 52. After the last patient completed week 52 and blinding was broken, the investigator could escalate golimumab to 100 mg and/or adjust MTX. The co–primary end points (week 24 American College of Rheumatology criteria for 50% improvement [ACR50] response and week 52 change in Sharp/van der Heijde score [SHS]) have been published previously. We now detail week 52 major secondary end points (Health Assessment Questionnaire [HAQ] disability index [DI] scores and SHS among patients with a baseline C-reactive protein [CRP] level >1.0 mg/dl) and week 104 findings. RESULTS: At week 52 for combined groups 3 and 4 versus group 1, the respective proportions of patients achieving ACR20 and ACR50 responses were 63.2% versus 51.9% (P = 0.017) and 45.3% versus 35.6% (P = 0.044). Respective week 52 mean HAQ DI improvements were 0.70 versus 0.58 (P = 0.053); mean SHS changes were 0.41 versus 1.37 (P = 0.006) among all patients and 0.74 versus 2.16 (P = 0.003) in patients with a CRP level >1.0 mg/dl. Improvements were maintained through week 104. Golimumab + MTX for 2 years yielded statistically less radiographic progression than initial MTX or golimumab 100 mg monotherapy. Golimumab safety profiles through weeks 24, 52, and 104 were generally consistent with those observed in other golimumab studies. CONCLUSION: In RA patients who had never taken MTX, up to 2 years of golimumab + MTX yielded sustained improvements in clinical signs/symptoms, physical function, and radiographic progression.
25172238 Methotrexate for the treatment of rheumatoid arthritis in the biologic era: still an "anch 2014 Nov The improvement of rheumatoid arthritis (RA) management has been strictly related to methotrexate (MTX) long-term effectiveness, safety profile and its widespread use in clinical practice over the last decades. According to the results of several head-to-head comparative trials against other synthetic DMARDs, MTX has been recognised as the "anchor drug" for the treatment of RA at the end of the 1990s. The subsequent increasing knowledge in the area of RA pathophysiology has progressively expanded the arsenal of available therapeutic tools, especially by the introduction of novel drugs such as biological DMARDs. The introduction of therapies targeted to key molecules and cells involved in RA pathogenesis has significantly changed the strategies for disease management, possibly modifying the key role of MTX. This review first analyses data supporting the evolution of MTX towards the role of "anchor drug" for RA in the pre-biologic era. We will then examine how the introduction and progressive spreading of biological agents could have modified the central role of MTX in the approach to RA.
23494713 Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more fre 2013 Apr We retrospectively analyzed in 54 consecutively enrolled Japanese patients with rheumatoid arthritis (RA) and lymphoproliferative disease (LPD) relevant clinicopathological characteristics, in particular paying attention to treatment with methotrexate (MTX). Between the 28 patients treated with MTX (MTX-treated group) and the 26 who were not (non-MTX group), there was no difference in age, interval between onset of RA and LPD, and lymphoma stage. Immunohistochemical analysis showed that in the MTX-treated group, 15 (53 %) patients had mature B-cell LPD, eight (29 %) mature T/NK-cell LPD, and five (18 %) had Hodgkin lymphoma. In the non-MTX group, 22 (84 %) had mature B-cell LPD, 2 (8 %) had mature T/NK-cell LPD, and 2 (8 %) had Hodgkin lymphoma. The frequency of mature T/NK-cell LPD was significantly higher in the MTX-treated group (p < 0.05). Of the eight patients in the MTX-treated group with mature T/NK-cell LPD, two had large granular lymphocytic leukemia and the other six had a variety of different histological types with frequent CD8 but not CD56 expression. Epstein-Barr virus (EBV) infection was significantly higher in the MTX-treated group (p < 0.05); evidence of latent type II EBV infection was found in four of the eight patients with mature T/NK-cell LPD. Withdrawal of MTX led to complete remission in seven patients with mature T/NK-cell LPD irrespective of EBV infection. Our findings highlight that mature T/NK-cell LPD is a frequent complication in RA patients treated with MTX. EBV infection may play a role in the pathogenesis of T/NK-cell LPD, as well as B-cell LPD and Hodgkin lymphoma in MTX-treated RA patients.
23835658 Cost-minimisation analysis of subcutaneous methotrexate versus biologic therapy for the tr 2013 Nov This study aims to model the economic impact of subcutaneous methotrexate (SC MTX) or a biologic over a 12-month period using a hypothetical population of rheumatoid arthritis patients who failed to tolerate or respond to oral MTX and were suitable candidates for biologic therapy. A decision-based model was developed using current National Institute for Health and Clinical Excellence (NICE) guidance to determine the management of this hypothetical UK population. Published data on the continuation rates of SC MTX and biologics were used to compare the costs of the two treatment options. The economic model used a cost-minimisation methodology from a UK National Health Service (NHS) perspective, with the cost of all drugs and resources being estimated on this basis. Sensitivity analyses were also performed to determine the effects of changing key assumptions on the mean cost differences. The routine use of SC MTX following oral MTX failure has the potential to save an estimated £7,197 per patient in the first year of therapy and £9.3m per year nationally in new patients. Sensitivity analyses support the robustness of the results. The results of this study suggest that routine use of SC MTX following oral MTX failure has the potential to provide considerable savings to the NHS through optimised use of MTX first-line therapy. It is proposed, therefore, that patients should start on oral MTX with a subsequent switch to SC MTX in the case of an insufficient response or tolerability issues, before introducing a biologic agent.
23925553 Improved radiological outcome of rheumatoid arthritis: the importance of early treatment w 2013 Dec The objective of this study is to compare the radiological progression in patients with rheumatoid arthritis (RA) diagnosed in the 1980s with those of the late 1990s until 2005 and to evaluate prognostic factors. Ninety-two RA patients who were firstly seen in our clinic from 1997 to 2005 were identified. As a control group, 89 RA patients from 1986 to 1990 were matched for the criteria disease duration (mean, 22 ± 17 months), age, and number of x-ray controls. Radiological damage was measured by the Ratingen score (RS). The baseline RS of the 1997-2005 group was significantly lower (mean, 3.8 ± 8.7 vs 7.7 ± 13.0; p < 0.0001) and showed less radiological progression during follow-up than the 1986-1990 group (ΔRS/year of 0.95 ± 2.19 vs. 5.69 ± 8.43; p < 0.0001). In the later group, more patients (73 vs. 28%) had methotrexate (MTX). Twenty-one (23%) of the patients in the later group received biological drugs. However, the subgroup 1997-2000 (n = 29), before the approval of TNF-inhibitors, had already lower baseline RS in comparison to 1986-1990 (2.7 ± 4.9; p < 0.001). Multivariate analysis showed that early start of MTX (before or directly after first consultation) was a predictor of favorable outcome (p < 0.005), as were low erythrocyte sedimentation rate at baseline and belonging to the later group. In contrast, neither treatment with glucocorticoids or biological drugs nor the overall rate of MTX or other disease-modifying antirheumatic drug use was predictive. Radiological damage is markedly diminished in RA patients seen since mid of the 1990s. Early treatment with MTX seems to be the key factor for this improved prognosis.
23992137 The decline in joint replacement surgery in rheumatoid arthritis is associated with a conc 2013 Aug BACKGROUND AND PURPOSE: Drug-based treatment of rheumatoid arthritis (RA) has evolved markedly over the past 2 decades. Using nationwide register data, we studied how this has affected the rates of hip, knee, shoulder, and elbow replacement from 1995 to 2010. METHODS: The number of primary joint replacements was obtained from the Finnish Arthroplasty Register. To test the hypothesis that improvements in medical treatment of RA reduce the need for joint replacements, we also collected data about purchases of different disease-modifying anti-rheumatic agents (DMARDs) and biological drugs from the nationwide drug registers. RESULTS: The annual incidence of primary joint replacements for RA declined from 19 per 10(5) in 1995 to 11 per 10(5) in 2010. The decline was greater for upper-limb operations than for lower-limb operations. At the same time, the numbers of individuals using methotrexate, hydroxychloroquine, and sulfasalazine (the most commonly used DMARDs) increased 2- to 4-fold. INTERPRETATION: Our results are in accordance with observations from other countries, and indicate that the use of joint replacements in RA has decreased dramatically. Our data suggest that effective medical therapy is the most likely explanation for this favorable development.