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ID PMID Title PublicationDate abstract
15778238 Magnetic resonance imaging for accelerated assessment of drug effect and prediction of sub 2005 Oct OBJECTIVES: By MRI to assess the efficacy of addition of anakinra for controlling synovitis and stopping erosive progression in patients with clinically active RA despite receiving methotrexate, and to determine the predictive value of MRI for subsequent radiographic erosive progression. METHODS: 100 mg anakinra subcutaneously/day was added to the treatment of 17 patients with clinically active RA despite methotrexate. MRI of the non-dominant wrist and 2nd-5th MCP joints (OMERACT evaluation) was performed at weeks 0, 12, and 36, and radiography of both hands and wrists (modified Sharp evaluation) at weeks 0 and 36. RESULTS: MRI synovitis scores were not significantly changed. Radiography of both hands and wrists after 36 weeks showed erosive progression in 11 patients, and MRI after 12 weeks in 10 patients. Nine of 10 patients with MRI progression at 12 weeks had radiographic progression at 36 weeks. Baseline MRI synovitis and erosion scores, but no clinical/biochemical parameters, correlated significantly with subsequent erosive progression. CONCLUSION: Addition of anakinra did not significantly reduce MRI signs of synovitis, and most patients had progressive joint destruction. Baseline MRI findings predicted subsequent radiographic erosive progression. Unilateral wrist and MCP joint MRI after 12 weeks had a similar sensitivity for detection of erosive progression as bilateral hand and wrist radiography after 36 weeks.
15748099 Efficacy, tolerability and cost effectiveness of disease-modifying antirheumatic drugs and 2005 Over the last decade, several new drugs have become available for the treatment of patients with rheumatoid arthritis. These agents include the new disease-modifying antirheumatic drug (DMARD) leflunomide and the biologic agents, tumor necrosis factor (TNF)-alpha antagonists and an interleukin (IL)-1 receptor antagonist. Methotrexate is commonly used as the first DMARD, has a well documented clinical efficacy and slows radiological deterioration. Sulfasalazine appears to have similar properties, albeit to a lesser extent. Leflunomide has similar efficacy as methotrexate but it is less tolerated than sulfasalazine. The adverse effect profiles of these three drugs makes regular laboratory monitoring mandatory. Several combination therapies with DMARDs were proven to be more effective than mono-DMARD therapy. However, until now these strategies have not been widely adopted. TNF antagonists are potent anti-inflammatory drugs, with a rapid onset of effects compared with traditional DMARDs. The IL-1 receptor antagonist, anakinra, has an intermediate place between methotrexate and the TNF antagonists with respect to efficacy. The adverse effects of TNF antagonists include an increased incidence of common and opportunistic infections. Thus far, anakinra has not been associated with an enhanced rate of opportunistic infections. Some of the biologic agents have been associated with worsening heart failure and demyelinating disease. The limited long-term safety data of the biologic agents are a point of concern because, at present, an enhanced risk for malignancies, particularly lymphoma, can not be excluded. Drug costs of traditional DMARDs are up to US dollars 3000 per year, whereas for the biologics the yearly drug costs range between US dollars 16,000 and > US dollars 20,000. Cost-effectiveness analyses are necessary to determine whether or not these high costs are justified. Unfortunately, adequate, prospective, economic evaluations are not yet available. Until these become available, treatment decisions will be based on the balance of direct costs and indirect costs and expected cost savings in the future.
15895881 Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis. 2005 Mar This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).
15641102 Very early treatment with infliximab in addition to methotrexate in early, poor-prognosis 2005 Jan OBJECTIVE: Anti-tumor necrosis factor alpha agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12-month double-blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor-prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months. METHODS: All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months. RESULTS: Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C-reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX-treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between-group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05). CONCLUSION: Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.
16095122 Methotrexate use in rheumatoid arthritis is associated with few clinically significant liv 2005 Jul OBJECTIVE: To determine the frequency of liver function tests (LFT) abnormalities associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis (RA). METHODS: A retrospective chart review for demographic information, RA-specific history, medication history, complications of therapy, results of all available blood tests (specifically aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), albumin, creatinine), and liver biopsy reports was conducted for RA patients, who were currently using or have used MTX in the past. RESULTS: A total of 2791 LFTs were performed among 182 RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT evaluations demonstrated no abnormal results, compared with 30 patients (16.5%) who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients with at least one LFT abnormality (73.3%) continued treatment despite the elevation without further evaluation or change in therapy, and subsequent LFT assessments were within normal limits. 128 patients (70.3%) remained on MTX at the time of our study. The most common reason for discontinuation was inadequate response. CONCLUSIONS: MTX appears to be associated with very few clinically significant hepatic side effects. In view of these data, consideration as to revision of the current MTX monitoring guidelines in the direction of less frequent monitoring, especially in patients with no risk factors for liver disease, may be considered.
17025376 Adalimumab: a review of its use in adult patients with rheumatoid arthritis. 2006 Adalimumab (Humira) is a recombinant, fully human anti-tumor necrosis factor (TNF) monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis (RA). In combination with methotrexate or standard antirheumatic therapy or as monotherapy, adalimumab effectively reduced signs and symptoms of RA, induced remission, improved physical function and inhibited the progression of structural damage in several randomized, double-blind, placebo-controlled phase III trials. The drug was generally well tolerated, with most adverse events being mild to moderate, and the serious adverse events profile being similar to that generally seen in patients with RA not receiving anti-TNF agents. Adalimumab was at least as cost effective as other anti-TNF agents used in the therapy of RA, and provided significant improvements in patients' health-related quality of life. Overall, adalimumab in combination with methotrexate or standard antirheumatic therapy is valuable as a first-line therapeutic option in patients with early, aggressive RA, and a second-line therapeutic option in patients with long-standing, moderate to severe RA. For the latter indication, adalimumab may also be used as monotherapy.
16040164 [Atherosclerosis and rheumatoid arthritis]. 2006 Feb AIMS: To identify studies which have shown that rheumatoid arthritis (RA) is associated with an increase in cardiovascular morbidity and mortality. To identify the different factors that may be involved. To consider what management would decrease the cardiovascular morbidity and mortality of RA. RESULTS: Epidemiological studies have shown that the risk of a cardiovascular event is increased twofold in RA patients irrespective of the traditional cardiovascular risk factors. Non-invasive methods have shown that RA patients have endothelial dysfunction, decreased arterial compliance and increased intima-media thickers, predictive factors for cardiovascular events in comparison to controls after controlling for traditional cardiovascular risk factors. The increased cardiovascular risk is directly mediated by inflammatory syndrome, which also indirectly increases the risk by inducing dyslipidemia and insulin resistance. Treatments also have a hamful effect, whether it be corticosteroid therapy, non-steroidal anti-inflammatory drugs (NSAIDs), or methotrexate (MTX), which leads to hyperhromocysteinemia. CONCLUSION: It should be possible to decrease cardiovascular morbidity and mortality by a strict control of the disease's activity. We should also take measures to combat other cardiovascular risk factors: as low a dose as possible for corticosteroid therapy, limited prescription of NSAIDs, systematic supplementation of MTX with folic acid encouragement of smoking cessation, regular lipid tests and prescription of statins treatment for hyperlipemia in accordance with current recommendations.
17040110 Remission, a therapeutic goal in inflammatory arthropathies? Clinical data from adalimumab 2006 In recent years, there have been major advances in the management of rheumatoid arthritis (RA), leading to the development of tumour necrosis factor (TNF) antagonists. With these agents, it is possible to arrest joint damage and, by treating early in the disease course, to prevent joint damage. It is also now thought that early treatment can achieve clinical remission in a substantial proportion of patients. With these increased expectations, a change is required in the way clinical improvement and drug efficacy is measured. The existing standard endpoint commonly used in RA clinical trials, the American College of Rheumatology (ACR) 20% response measure, is inadequate for the new goals of therapy that should be based on clinical remission and radiographic assessment.Adalimumab, a fully human anti-TNF monoclonal antibody, has been shown to be effective in achieving remission and preventing radiographic progression of joint damage in patients with RA and other inflammatory arthropathies, including psoriatic arthritis and ankylosing spondylitis. In a placebo-controlled trial in patients with early RA, combination treatment with adalimumab plus methotrexate (MTX) has been shown to be superior to either treatment alone in inducing significant clinical remission while being generally well tolerated. Compared with monotherapy, combination therapy resulted in significantly more patients (49% vs 25%; p < 0.001) remaining in clinical remission after 2 years. Suppression of joint damage assessed by the degree of inhibition of radiographic progression was also significantly higher for patients treated with adalimumab plus MTX (and with adalimumab alone) at 6 months, 1 and 2 years than for those treated with MTX alone. These data support the notion that clinical remission is a realistic therapeutic goal in patients with RA.
16729012 Lupus anticoagulant and ischemic myocardial microangiopathy in rheumatoid arthritis. 2006 Jun BACKGROUND: A 49-year-old man presented at a hospital with an arthritic flare-up and stress dyspnea with a cough. He had a 5-year history of symmetrical polyarthritis, for which he was prescribed 5-15 mg prednisolone daily. He was subsequently diagnosed with rheumatoid arthritis and prescribed 20 mg methotrexate weekly, 3 mg/kg ciclosporin daily and 5 mg prednisolone daily. Infliximab therapy was initiated after 3 months because of persistent joint pain and inflammation. Six months later, however, the patient was readmitted to hospital with a new arthritic flare-up, acute retrosternal chest pain and stress dyspnea. INVESTIGATIONS: Laboratory analyses, electrocardiography, chest radiography, high-resolution CT, echocardiography, technetium-99m-labeled (99mTc)-methoxyisobutyl-isonitrile stress myocardial scintigraphy and coronary angiography. DIAGNOSIS: Lupus anticoagulant and ischemic myocardial microangiopathy. MANAGEMENT: Drug therapy with prednisolone, methotrexate, anakinra, aspirin and clopidogrel.
15960817 B cell targeted therapies. 2005 Although the precise pathogenesis of rheumatoid arthritis (RA) remains unclear, many cell populations, including monocytes, macrophages, endothelial cells, fibroblasts and B cells, participate in the inflammatory process. Ongoing research continues to evaluate the critical roles played by B cells in sustaining the chronic inflammatory process of RA. These findings have contributed to the development of targeted therapies that deplete B cells, such as rituximab, as well as inhibitors of B lymphocyte stimulation, such as belimumab. In a phase I trial, belimumab treatment significantly reduced CD20+ levels in patients with systemic lupus erythematosus. Phase I and phase II trials of rituximab found that rituximab plus methotrexate achieved significantly better American College of Rheumatology 50% responses for patients with RA than those patients receiving monotherapy with methotrexate. These clinical trial data present promising evidence for B cell targeted therapies as future therapeutic options for RA.
17083767 Aiming at low disease activity in rheumatoid arthritis with initial combination therapy or 2006 Nov AIM: To evaluate the efficacy and safety of four different treatment strategies for patients with early rheumatoid arthritis (RA). METHODS: In the BeSt study, 508 patients with newly diagnosed (< 2 years) active RA were randomised to be treated according to four treatment strategies: 1. sequential monotherapy, 2. step up to combination therapy (both starting with methotrexate), 3. initial combination therapy with methotrexate, sulphasalazine, and a tapered high dose of prednisone, and 4. initial combination therapy with methotrexate and infliximab. Three-monthly therapy adjustments were dictated by calculation of the Disease Activity Score (DAS), with the goal to achieve and maintain a DAS
17136752 Immunosuppressive medications and hospitalization for cardiovascular events in patients wi 2006 Dec OBJECTIVE: The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA), most likely because of increased systemic inflammation. Prior research suggests that immunosuppressive medications may reduce the risk of CVD among RA patients. This study was undertaken to investigate the effects of various immunosuppressive medications on the risk of cardiovascular events among a group of older patients with RA. METHODS: In this nested case-control study, the source cohort was derived from Medicare beneficiaries receiving a drug benefit from the state of Pennsylvania. These individuals were required to have been diagnosed as having RA on at least 2 visits and to have filled a prescription for an immunosuppressive agent. Cases were defined as those patients who were hospitalized for a cardiovascular event such as myocardial infarction or stroke, and 10 control subjects were matched to each case by age, sex, and calendar year of the index date (the time of the first cardiovascular event in each case). Current use of an immunosuppressive medication was defined as having filled a prescription for these agents within the 90 days prior to the index date. Multivariate logistic regression models that included important covariates were assessed to determine the risk of cardiovascular events associated with immunosuppressive agents and their combinations. RESULTS: Among the study cohort, we identified 3,501 RA patients who fulfilled our eligibility criteria. During followup of this cohort, 946 patients were hospitalized for a cardiovascular event. Although the 95% confidence intervals (95% CIs) were wide in adjusted risk regression models with methotrexate (MTX) monotherapy as the reference group, biologic immunosuppressive agents showed neither protective nor deleterious effects (with biologics monotherapy, odds ratio [OR] 1.0, 95% CI 0.5-1.9; with biologics plus MTX combination therapy, OR 0.8, 95% CI 0.3-2.0; and with biologics plus other immunosuppressive agents, OR 1.2, 95% CI 0.7-2.2). Monotherapy with oral glucocorticoids was associated with an increased risk of cardiovascular events (OR 1.5, 95% CI 1.1-2.1), and a similar trend in the direction of risk was seen with glucocorticoid combination therapy (OR 1.3, 95% CI 0.8-2.0). Cytotoxic immunosuppressive agents other than MTX (azathioprine, cyclosporine, and leflunomide) were also associated with an increased risk of cardiovascular events (with both monotherapy and combination treatment, OR 1.8, 95% CI 1.1-3.0). CONCLUSION: When compared with RA patients receiving MTX monotherapy, those receiving biologic immunosuppressive agents had neither an increased nor decreased risk of experiencing a cardiovascular event, whereas use of oral glucocorticoids and cytotoxic immunosuppressive agents was associated with significant increases in the risk of cardiovascular events.
16572284 Durable remission of HIV-negative, Kaposi's sarcoma herpes virus-associated multicentric C 2007 Jul Multicentric Castleman disease (MCD) is a nonneoplastic lymphoproliferative disorder that has a poor prognosis. Optimal treatment is unknown. There are a few reported cases of MCD and rheumatoid arthritis. In this study, we report a patient with rheumatoid arthritis diagnosed with Kaposi's sarcoma herpesvirus-(KSHV, human herpesvirus-8) associated MCD that showed expression of viral IL-6. Treatment with methotrexate (MTX) resulted in a complete remission of her disease lasting for 54+ months. Multiple studies have suggested that MCD and rheumatoid arthritis are associated with overexpression of the growth-promoting cytokine interleukin-6 (IL-6), and that MTX downregulates the production of this cytokine in vivo. As such, we suggest that the dramatic improvement in this patient's disease is due to the immunomodulatory properties of MTX.
16932507 A case of late-onset chorea. 2005 Dec Background A 75-year-old woman with rheumatoid arthritis presented with a 4-year history of chorea to a hospital movement disorder clinic. The involuntary movements were initially mild, affecting only the right side of the body, but gradually worsened and became bilateral. There was no relevant family history. Medications included hormone replacement therapy (HRT), diclofenac sodium, vitamin D, folic acid, methotrexate and zopiclone. On examination, bilateral choreiform movements were seen, affecting the face and limbs, with the right side more severely affected than the left. Investigations Neuropsychological testing, laboratory blood and DNA testing, echocardiogram, MRI of the brain, and brain perfusion single-photon emission computed tomography (SPECT) scanning.Diagnosis HRT-related chorea, possibly caused by a predisposition secondary to rheumatoid arthritis and small-vessel ischemic disease, or subclinical childhood rheumatic fever. Management Discontinuation of HRT.
16785475 Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: 2006 Jun 20 BACKGROUND: The selective co-stimulation modulator abatacept demonstrated efficacy for treating rheumatoid arthritis in early clinical studies. OBJECTIVE: To evaluate the effects of abatacept in patients with persistent, active rheumatoid arthritis despite methotrexate treatment. DESIGN: One-year, multicenter, randomized, double-blind, placebo-controlled trial (November 2002 to October 2004). SETTING: 116 centers worldwide. PATIENTS: 652 patients with active rheumatoid arthritis despite methotrexate treatment. INTERVENTION: Once-monthly infusion of a fixed dose of abatacept, approximately 10 mg/kg of body weight, or placebo. MEASUREMENTS: Co-primary end points were a 20% improvement in American College of Rheumatology (ACR) response criteria (ACR 20) at 6 months, clinically meaningful improvements in physical function, and change from baseline in joint erosion score at 1 year. RESULTS: Four hundred thirty-three and 219 patients were randomly assigned to abatacept or placebo, respectively, and 385 (89%) and 162 (74%), respectively, completed 1 year of treatment. In a modified intention-to-treat analysis, 6-month ACR 20, ACR 50, and ACR 70 responses were 67.9% for abatacept versus 39.7% for placebo (difference, 28.2 percentage points [95% CI, 19.8 to 36.7 percentage points]), 39.9% for abatacept versus 16.8% for placebo (difference, 23.0 percentage points [CI, 15.0 to 31.1 percentage points]), and 19.8% for abatacept versus 6.5% for placebo (difference, 13.3 percentage points [CI, 7.0 to 19.5 percentage points]), respectively. At 1 year, the responses increased to 73.1% for abatacept versus 39.7% for placebo (difference, 33.4 percentage points [CI, 25.1 to 41.7 percentage points]), 48.3% for abatacept versus 18.2% for placebo (difference, 30.1 percentage points [CI, 21.8 to 38.5 percentage points]), and 28.8% for abatacept versus 6.1% for placebo (difference, 22.7 percentage points [CI, 15.6 to 29.8 percentage points]), respectively (P < 0.001 for all). Physical function significantly improved in 63.7% versus 39.3% of patients (P < 0.001). At 1 year, abatacept statistically significantly slowed the progression of structural joint damage compared with placebo. Abatacept-treated patients had a similar incidence of adverse events (87.3% vs. 84.0%; difference, 3.3 percentage points [CI, -2.5 to 9.1 percentage points]) and a higher incidence of prespecified serious infections (2.5% vs. 0.9%; difference, 1.6 percentage points [CI, -0.3 to 3.6 percentage points]) and infusion reactions (acute, 8.8% vs. 4.1%; difference, 4.7 percentage points [CI, 0.9 to 8.4 percentage points]; peri-infusional, 24.5% vs. 16.9%; difference, 7.6 percentage points [CI, 1.2 to 14.0 percentage points]) compared with placebo recipients. LIMITATIONS: The study involved only 1 group of patients over 1 year. CONCLUSIONS: Abatacept statistically significantly reduced disease activity in patients with rheumatoid arthritis and an inadequate response to methotrexate. Longer treatment in different patient populations is needed to establish its appropriate role in rheumatoid arthritis.
16083527 Methotrexate dosage reduction in patients with rheumatoid arthritis beginning therapy with 2005 Aug OBJECTIVE: Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered. METHODS: Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure. RESULTS: Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54. CONCLUSION: Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.
16798046 Recommendations of the French Society for Rheumatology. TNFalpha antagonist therapy in rhe 2006 Jul OBJECTIVES: To develop recommendations for TNFalpha-antagonist therapy in patients with rheumatoid arthritis (RA) seen in everyday practice, under the aegis of the French Society for Rheumatology. METHOD: We used the methods recommended by the French Agency for Healthcare Accreditation and Evaluation, the AGREE collaboration, and the European League against Rheumatism (EULAR). The recommendations focus on patient selection, monitoring, and treatment adjustments. RESULTS: Criteria for selecting patients eligible for TNFalpha-antagonist treatment of RA include: 1) a definitive diagnosis of RA; 2) disease activity for longer than 1 month, including presence of objective signs of inflammation; or radiographic progression; 3) previous failure of methotrexate in the highest tolerated dosage or of another disease-modifying antirheumatic drug in patients with contraindications to methotrexate; 4) absence of contraindications to TNFalpha-antagonist therapy. When starting TNFalpha-antagonist therapy 1) a thorough baseline evaluation should be conducted; 2) any of the three available agents can be used, as no differences in efficacy have been identified in patient populations; 3) concomitant methotrexate therapy is recommended regardless of the TNFalpha antagonist used; and 4) patients should receive standardized follow-up at regular intervals. Treatment adjustments should be based on the following: 1) the treatment objective is achievement of a EULAR response; 2) when such a response is not achieved, the dosage or dosing interval can be changed, or the patient can be switched to another TNFalpha antagonist; 3) in patients who experience intolerance to a TNFalpha antagonist, another TNFalpha antagonist may be tried, depending on the nature of the adverse event; 4) occurrence of a remission should lead to a reduction in symptomatic medications, most notably glucocorticoids where used; in the event of a prolonged remission, either the TNFalpha antagonist or the concomitant disease-modifying antirheumatic drug may be reduced. CONCLUSION: These recommendations are intended to help physicians use TNFalpha antagonists in their everyday practice with RA patients. They do not constitute regulations.
16541481 Etanercept treatment in adults with established rheumatoid arthritis: 7 years of clinical 2006 May OBJECTIVE: To evaluate safety and efficacy of longterm etanercept treatment in patients with disease modifying antirheumatic drug (DMARD) refractory rheumatoid arthritis (RA). METHODS: Safety results are reported for 714 patients who received etanercept in one of 7 initial trials or a longterm extension. Efficacy results are reported for 581 patients who enrolled in the extension. RESULTS: Of the 714 patients enrolled in the initial trials, 581 (81%) enrolled in the extension, and 388 (54%) patients are continuing to receive etanercept therapy. The longest individual treatment was 8.2 years, with 3139 total patient-years of etanercept exposure. Rates of serious adverse events (overall rate=14.8 events/100 patient-yrs), serious infections (overall rate=4.2 events/100 patient-yrs), cancer (overall rate=1.0 events/100 patient-yrs), and deaths (overall rate=0.7 events/100 patient-yrs) were stable each year, through 8 years of etanercept exposure. For 356 patients who completed 6 years of etanercept treatment, response rates were ACR20=73%, ACR50=52%, ACR70=27%, DAS28 CRP good response=52%, and DAS28 CRP remission=37% of patients. Similar responses occurred in 167 patients who completed Year 7. Doses of concomitant methotrexate or corticosteroids were reduced in many patients who maintained clinical responses. CONCLUSION: The safety profile of etanercept was consistent over time, with rates of adverse events similar to those reported for patients with RA in general. Durable clinical responses were observed in some patients for 7 years or more. The benefit-to-risk ratio for longterm etanercept treatment remains highly favorable.
16030083 The changing use of disease-modifying anti-rheumatic drugs in individuals with rheumatoid 2005 Nov OBJECTIVES: To describe the use of disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) and changing trends in their use. METHODS: We used the General Practice Research Database (GPRD) to describe DMARD use by patients with RA identified using ICD-9 codes. The GPRD is a UK national database containing records of more than 7 million individuals from 683 general practices. Subjects were studied between 1987 and 2002. The prevalence and duration of individual DMARD use and changing trends in DMARD use were investigated. RESULTS: Thirty-four thousand three hundred and sixty-four patients with RA were identified. Only 17,115 (50%) individuals were prescribed at least one DMARD during the study period. The most commonly prescribed DMARD over the study period was sulphasalazine (46.3%) and then methotrexate (31.4%). Use of methotrexate has increased 17-fold (1.8% of all DMARD prescriptions in 1988 to 30% in 2002) whereas use of gold has fallen (13.2% to 2.3%). Analysis of DMARD persistence using Kaplan-Meier survival curves showed the methotrexate use persisted significantly longer than other DMARDs with an estimated median of 8.1 yr. Prednisolone was used in up to 50% of RA patients in any one year and has remained fairly constant throughout the study period. CONCLUSIONS: Large numbers of individuals with a clinical diagnosis of RA identified from a large primary care database are not receiving DMARDs. This work suggests that many individuals with RA have not been treated appropriately and this may have major long-term consequences on joint damage and general health.
16504991 Down regulation of multidrug resistance protein-1 expression in patients with early rheuma 2006 Oct BACKGROUND: Methotrexate (MTX) is the current gold standard conventional disease-modifying antirheumatic drug (DMARD) and is effluxed from cells by several transmembrane proteins, including multidrug resistance protein-1 (MRP1). It is hypothesised that the overexpression of these proteins may mediate reduced efficacy of MTX. To date, it is unclear how expression of these proteins changes over time or after exposure to drugs. AIMS: To compare MRP1 expression in newly diagnosed patients with DMARD-naive rheumatoid arthritis with that in healthy controls and to investigate how MRP1 expression changed after exposure to MTX. METHODS: 18 newly diagnosed patients with DMARD-naive rheumatoid arthritis and 14 healthy controls were recruited. Peripheral blood mononuclear cell counts were taken at baseline and after 6 months' treatment with MTX. Cells were separated by density gradient centrifugation and MRP1 expression was measured using the QCRL-1 monoclonal antibody. RESULTS: MRP1 expression in patients did not seem to be up regulated compared with that in healthy controls. In patients who were positive for MRP1 at baseline (61%), treatment with MTX and folic acid led to a marked down regulation of MRP1 expression at 6 months. CONCLUSION: In patients with rheumatoid arthritis expressing MRP1, treatment with MTX and folic acid led to down regulation of MRP1 expression. Further studies are required to determine the mechanism behind this observation and whether MRP1 expression mediates altered efficacy to MTX.