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ID PMID Title PublicationDate abstract
16091838 Pulmonary involvement in lifelong non-smoking patients with rheumatoid arthritis and ankyl 2006 Mar Pulmonary involvement seen in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has been detected increasingly by using highly sensitive diagnostic techniques such as high-resolution computed tomography (HRCT). However, HRCT findings in healthy controls and the effects of smoking and drugs have not been well studied. The aim of this controlled study was to evaluate the relationships between disease-specific clinical, laboratory, HRCT and pulmonary function test (PFT) findings in 20 RA patients using methotrexate (MTX) and 20 AS patients using sulphasalazine who were non-smokers and exhibited asymptomatic respiratory signs. For this purpose, a total of 60 persons (40 patients and 20 healthy controls) were included in this study. A restrictive pattern on PFT was detected in four patients (20%) with AS, one patient with RA and one control (p<0.05). Fourteen patients (70%) with RA and ten patients (50%) with AS had positive HRCT findings. Only one patient (5%) in the control group had abnormal HRCT findings (p<0.05). Interstitial lung disease (ILD) was the most frequently seen HRCT finding in both the RA (35%) and AS (20%) groups. The chest expansion measurement, the score of the visual analogue scale (VAS) for pain and C-reactive protein (CRP) levels were statistically significantly better in patients with AS having normal HRCT than in those with abnormal findings (p<0.05). There was no correlation detected between HRCT and duration of disease, disease activity markers, functional indexes and PFT in patients with RA and AS. HRCT is a sensitive tool in detecting ILD in patients with RA and AS with no signs and symptoms of pulmonary involvement and may be an integral part of such work-up. However, future prospective studies are needed to better determine if HRCT is in fact a predictor of subsequent MTX toxicity.
16855169 Bone metabolism changes during anti-TNF-alpha therapy in patients with active rheumatoid a 2006 Jun Osteoporosis (OP) occurs more frequently in patients with rheumatoid arthritis (RA) than in healthy individuals. Specific treatments of RA may increase susceptibility to OP, but at the same time decrease inflammatory activity, which is associated with accelerated bone loss. Treatment with TNF-alpha blockers might influence bone metabolism and prevent structural bone damage in RA, in particular at the periarticular level. Our aim was to assess the influence of anti-TNF-alpha therapy on bone metabolism in RA patients. To that end we evaluated a group of 30 RA patients [mean age 50.6 +/- 6.8 years; median disease duration 82 +/- 38 months; median disease activity score (DAS-28) 5.8 +/- 1.2: 70% of whom were positive for the rheumatoid factor IgM (>40 IU/mL)]. Patients were treated with stable therapy of prednisone (7.5 mg/day) and methotrexate (MTX = 10 mg/week). Eleven of these RA patients further received etanercept (25 mg, twice/weekly) and 10 infliximab (3 mg/kg on 0, 2, 6, and every 8 weeks thereafter). A control group included 10 RA patients with stable therapy (prednisone and MTX) and without anti-TNF-alpha therapy. All the patients fulfilled the ACR criteria for the diagnosis of adult RA and were treated for 6 months. Quantitative ultrasound (QUS) bone densitometry was performed at the metaphyses of the proximal phalanges of both hands with a DBM Sonic 1200 QUS device (IGEA, Carpi, Italy). Amplitude-dependent speed of sound (AD-SoS) was evaluated at base line and at 3 and 6 months. Bone mineral density (BMD) of the hip and lumbar spine (L1-L4) was determined by a densitometer (GE Lunar Prodigy, USA) at base line at after 6 months. Soluble bone turnover markers [osteocalcin (BGP) and deoxypyridinoline/creatinine (Dpd/Cr) ratio] were measured in all patients at the same times, using enzyme-linked immunosorbent assay tests. All data were compared using Wilcoxon signed rank test. Results were as follows: AD-SoS values were found increased by 1.3% after 6 months of treatment in the RA patients treated with anti-TNF-alpha therapy. On the contrary, the Ad-SoS levels decreased by 4.6% during the same period in the untreated RA group. BMD increased by 0.2% at lumbar spine and 0.1% at the hip in TNF-alpha-blocker-treated patients and decreased by 0.8% and 0.6% (at lumbar spine and at the hip, respectively) in RA patients without anti-TNF-alpha therapy. However, BMD variations were not significant. In RA patients treated with TNF-alpha blockers, BGP levels were found significantly increased (14.8 +/- 3.8 mg/mL vs. 22.4 +/- 4.2 mg/mL; P < 0.01) and Dpd/Cr levels were found significantly decreased (8.2 +/- 2.1 nM vs. 4.6 +/- 1.8 nM; P < 0.01) at 6 months when compared to base line values. On the contrary, there were no significant differences in the untreated RA patients concerning these latter parameters (BGP = 12.2 +/- 3.1 mg/mL vs. 10.8 +/- 2.8 mg/mL and Dpd/Cr = 8.9 +/- 2.4 nM vs. 10.2 +/- 1.8 nM, respectively). In conclusion, during 6 months of treatment of RA patients with TNF blockers, bone formation seems increased while bone resorption seems decreased. The reduced rate of OP appears to be supported by the same mechanisms involved in the decreased bone joint resorption during anti-TNF-alpha therapy, that is, the marked decrease of the proinflammatory (i.e., TNF-alpha) cytokine effects on bone metabolism.
18061981 Anti-tumor necrosis factor-alpha response in rheumatoid arthritis is associated with an in 2008 Jan OBJECTIVE: Patients with rheumatoid arthritis (RA) display high serum concentrations of soluble CD30 (sCD30), which correlate with counter-regulatory activity of CD30+ T cells in the inflamed joint. To verify the contribution of this T cell subset to disease remission, sCD30 levels were analyzed longitudinally in patients with active RA following infliximab therapy. METHODS: Infliximab plus methotrexate were started in 39 patients with active RA, while 20 patients with inactive disease, controlled by stable doses of methotrexate, acted as controls. Serial evaluations of sCD30 concentrations and disease activity indexes were performed throughout 38 weeks. RESULTS: sCD30 levels were higher in patients than in healthy controls. Rapid infliximab-induced decrease in disease activity was associated with an overall increase of sCD30 levels. In contrast, levels remained stable in controls. An inverse correlation between sCD30 levels and Disease Activity Score 28 was observed from the 22nd week of infliximab treatment. Analysis of sCD30 levels according to American College of Rheumatology response showed, after an initial general enhancement of sCD30 concentrations, a persistent increase of sCD30 in responders, but not in nonresponders. CONCLUSION: sCD30 serum levels are enhanced by tumor necrosis factor-a (TNF-a) blockade in patients with active RA and inversely correlated with disease activity, but only after some weeks of treatment. Of interest, a sustained increase of sCD30 is present only in subjects with evidence of persistent clinical response to anti-TNF-alpha. As sCD30 serum levels mirror antiinflammatory activity of joint T cells, the present data may suggest a role of synovial counter-regulatory CD30+ T cells in the induction of infliximab-mediated remission in RA.
18802706 Efficacy of tacrolimus in infliximab-refractory progressive rheumatoid arthritis. 2009 Feb We report a Japanese male patient with intractable rheumatoid arthritis (RA), in whom tacrolimus was effective ultimately. Five years before the admission he was diagnosed as RA, which was resistant to various disease-modifying anti-rheumatic drugs (DMARDs). Two years before, administration of infliximab was initiated although the medicine failed to control RA. In spite of the multiple joint replacement, the RA disease activity worsened. Tacrolimus (1.5 mg/day) was administered. Twenty-four weeks of tacrolimus treatment reduced the disease activity score for 28 joints-erythrocyte sedimentation rate from 7.44 to 3.65. Herein, we present a patient with RA, who was successfully treated by tacrolimus, and in whom infliximab was not effective. Tacrolimus may be one of the drugs for RA patients refractory to the conventional treatments including methotrexate or tumor necrosis factor inhibitors.
18787830 Effects of leflunomide and methotrexate in rheumatoid arthritis detected by digital X-ray 2009 Jan The aim of the present study was to evaluate the effect of long-term leflunomide and methotrexate (MTX) therapy during the course of rheumatoid arthritis (RA) estimated by digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) as diagnostic tools for the quantification of disease-related periarticular osteoporosis and joint space narrowing. Fourty matchable patients with verified RA were treated with leflunomide or MTX during an observation period of 2.5 years. All patients underwent complete computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR as well as semi-automated measurements of joint space widths (JSW) at the metacarpophalangeal articulations (MCP, thumb to small finger) and proximal interphalangeal joints (PIP, index finger to small finger) using digitized hand radiographs. DXR-BMD revealed an increase of 0.4% (leflunomide-group) versus a reduction of -9.1% (MTX-group). Regarding DXR-MCI, a reduction of -1.1% (leflunomide-group) and -5.3% (MTX-group) was observed. The CAJSA parameters showed a decline of -2.7% (JSW-MCP) versus -2.1% (JSW-PIP) in patients treated with leflunomide. An accentuated joint space narrowing was revealed (JSW-MCP: -5.7%; JSW-PIP: -6.2%) in the MTX group. Digital X-ray radiogrammetry and CAJSA could discriminate the influence of different therapeutic regimes on periarticular osteoporosis and joint space narrowing showing a less accentuated radiographic progression in patients treated with leflunomide.
18563514 A case of autoimmune hepatitis exacerbated by the administration of etanercept in the pati 2008 Aug A 50-year-old woman was admitted for active rheumatoid arthritis (RA). She was found to have RA 1 year prior to this admission. Past history was unremarkable and she had no family history for rheumatic diseases. As nonsteroidal anti-inflammatory drug (NSAID) and methotrexate were not effective, etanercept was started (25 mg, twice a week). Mild elevation of alanine transaminase (ALT) and aspartate transaminase (AST) was found as an outpatient, and it was considered to be NSAID-induced liver injury. Two weeks after the first dose of etanercept, she developed progressive elevation of AST and ALT with right upper quadrant tenderness and hepatomegaly. Etanercept was discontinued and liver biopsy was performed, which demonstrated portal-area-dominant lymphoplasmacytic inflammatory cell infiltration. She was diagnosed as autoimmune hepatitis (AIH). Glucocorticoid was started with normalized liver function and stable joint symptoms. AIH was thought to be acutely aggravated by the administration of etanercept.
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.
17278018 The serum concentration of infliximab in cases of autologous blood donation for patients w 2007 Our aim was to determine whether the use of infliximab for rheumatoid arthritis (RA) patients is associated with an increased rate of postoperative complications. In this study we evaluated the serum concentration of infliximab to study the influence of autologous blood donation (AB donation) in patients who were administered infliximab and underwent total knee replacement (TKR). We examined five RA patients. Infliximab combined with methotrexate was administered at 3 mg/kg every 8 weeks for all patients. We carried out the TKR operation in the middle of the 8-week interval in which infliximab was administered. The AB donation consisted of 400 ml pooled AB drawn at one point 2 weeks following the final administration of infliximab. Serum infliximab levels were measured using an enzyme-linked immunosorbent assay. Mean serum infliximab levels were 5.46 +/- 5.62 microg/ml 2 weeks after the final administration of infliximab, 2.02 +/- 1.66 microg/ml just before the operation, and 1.48 +/- 1.31 microg/ml 1 day post operation. Moreover, the mean serum level in an autologous blood bag sampled just before AB donation was 5.02 +/- 4.79 microg/ml. This study indicated the serum level of infliximab in the stored blood remained at almost the same level as the collected autologous blood. However, even after autotransfusion those levels were decreased compared with levels measured just before the operation. Therefore, we conclude that there is little influence of AB donation on the risks of infliximab.
18468723 A report of Epstein-Barr virus-positive primary cutaneous natural killer-/T-cell lymphoma. 2008 Jul We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.
18408246 Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arr 2009 Mar OBJECTIVE: To explore the effects of anti-tumour necrosis factor (TNF)alpha antibody therapy on bone mineral density (BMD) of the lumbar spine and femur neck in patients with rheumatoid arthritis (RA). METHODS: A total of 50 patients with active RA (DAS28> or =3.2) who started adalimumab (40 mg subcutaneously/2 weeks) were included in an open label prospective study. All patients used stable methotrexate and were allowed to use prednisone (< or =10 mg/day). The BMD of the lumbar spine and femur neck was measured before and 1 year after start of treatment. RESULTS: Disease activity at baseline (28-joint Disease Activity Score (DAS28)) and disease duration were inversely correlated with femoral neck BMD and lumbar spine BMD (p<0.05). Mean BMD of lumbar spine and femur neck remained unchanged after 1 year of adalimumab therapy (+0.3% and +0.3%, respectively). Of interest, a beneficial effect of prednisone on change in femur neck BMD was observed with a relative increase with prednisone use (+2.5%) compared to no concomitant prednisone use (-0.7%), (p = 0.015). CONCLUSION: In contrast to the progressive bone loss observed after conventional disease-modifying antirheumatic drug therapy, TNF blockade may result in an arrest of general bone loss. Consistent with previous observations, the data also suggest that the net effect of low-dose corticosteroids on BMD in RA may be beneficial, possibly resulting from their anti-inflammatory effects.
18821658 Effect of the early use of the anti-tumor necrosis factor adalimumab on the prevention of 2008 Oct 15 OBJECTIVE: To compare work disability and job loss in early rheumatoid arthritis (RA) patients receiving adalimumab plus methotrexate (adalimumab + MTX) versus MTX alone. METHODS: In this multicenter, randomized, controlled trial, patients with RA for <2 years who had never taken MTX and who self-reported work impairment were randomized to adalimumab + MTX or placebo + MTX for 56 weeks. Primary outcome was job loss of any cause and/or imminent job loss at or after week 16. Secondary outcomes included disease activity, function (Health Assessment Questionnaire [HAQ] score), and RA quality of life (RAQoL) questionnaire score. Work was evaluated with work diaries and the RA Work Instability Scale. RESULTS: Although job loss during the 56-week study was significantly lower with adalimumab + MTX (14 of 75 patients) compared with MTX alone (29 of 73 patients; P=0.005), the primary end point was not met (12 of 75 versus 20 of 73 patients; P=0.092), likely owing to early drop out in the MTX group. There were significant improvements in American College of Rheumatology 20% response criteria, 28-joint Disease Activity Score, DeltaHAQ, DeltaRAQoL, and working time lost in the adalimumab + MTX group. Twenty-four serious adverse events were reported in 17 participants, with no differences between groups. CONCLUSION: Adalimumab + MTX reduced job loss and improved productivity in early RA when compared with MTX alone, which supports the early use of anti-tumor necrosis factor therapy and suggests its cost efficacy.
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.
19128344 Improving patient outlook in rheumatoid arthritis: experience with abatacept. 2008 Oct PURPOSE: To examine the importance of improving patient outlook in rheumatoid arthritis (RA) and to discuss the role of the nurse practitioner (NP) who, through the assessment of patient-reported outcomes and in acting as an advocate for the patient with the wider healthcare team, has a crucial part to play in managing the overall well-being of the patient. This article will draw on the clinical experience to date with abatacept, a first-in-class therapy that has been approved for the treatment of RA in patients with an inadequate response to either traditional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, or biological DMARDs, such as tumor necrosis factor-alpha antagonists. DATA SOURCES: A comprehensive literature search was performed using the National Library of Medicine (MEDLINE), EMBASE, and BIOSIS databases (restricted to articles posted between January 2000 and February 2007) with the search terms CTLA-4Ig, abatacept, and primary clinical trial publications in patients with RA. The clinical data are summarized in this review along with safety data presented in the prescribing information. CONCLUSIONS: Recent changes in the approach to RA treatment, particularly the advent of biological therapies, have impacted the role of the NP. The role of the NP is integral to the management of RA and in maximizing patient outcomes, through educating patients to make informed choices regarding their treatment, ensuring the safe administration of therapies and monitoring response to therapy, and in acting as an advocate for the patient within the wider healthcare team. IMPLICATIONS FOR PRACTICE: The use of more patient-centered measures of response are gaining increasing importance both in clinical trials and in clinical practice, and as such the NP has an important role in ensuring that both the physical and the psychological needs of patients are met. Clinical trials to date have shown that abatacept provides significant and clinically meaningful improvements in patient-reported outcomes, as well as demonstrating significant clinical benefits and a consistent safety profile, thus representing a valuable treatment option within the RA treatment armamentarium.
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.
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.
17530705 A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in re 2007 Jun OBJECTIVE: To develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Two hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS < or = 2.4 at 6 months) and nonresponders. In case of differences, a stepwise selection procedure identified the predictors for response. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of patients. RESULTS: The model for MTX efficacy consisted of sex, rheumatoid factor and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and MTHFD1 genes. This prediction model was transformed into a scoring system ranging from 0 to 11.5. Scores of < or = 3.5 had a true positive response rate of 95%. Scores of > or = 6 had a true negative response rate of 86%. Sixty percent of the patients were categorized as either responders or nonresponders, whereas 32% of the patients were categorized using a nongenetic model. Evaluation of the model in 38 additional patients with RA supported the results. CONCLUSION: This study established a model for predicting the efficacy of MTX in patients with RA. This pharmacogenetic model may lead to better-tailored initial treatment decisions in patients with RA.
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.