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ID PMID Title PublicationDate abstract
16969149 Removal of methotrexate by peritoneal dialysis and hemodialysis in a single patient with e 2006 Sep BACKGROUND: Although methotrexate is highly bound to albumin, it is thought to be removed by hemodialysis and not by peritoneal dialysis. We are not aware of any direct comparison in the same patient. CASE REPORT/METHODS: A 60-year-old patient on continuous ambulatory peritoneal dialysis was admitted to the East Alabama Medical Center for stomatitis and pancytopenia after being given 10 mg of methotrexate for his rheumatoid arthritis. Measurements of total methotrexate levels were made before, during, and after sequential peritoneal and hemodialysis treatments. RESULTS: We found that the clearance of methotrexate measured in the dialysate was equal in the first hour of dialysis for both types of dialysis, although serum levels were markedly lower in hemodialysis compared to peritoneal dialysis. CONCLUSION: Methotrexate was cleared by peritoneal dialysis in the first hour of an exchange and was not associated with a rebound in serum levels. Hemodialysis was associated with lower serum levels; however, there was also a significant rebound 2 hours after the procedure ended. Since neither procedure was able to preclude the death of the patient, other more effective means of methotrexate elimination should be employed.
16265686 Modification of pro- and antiinflammatory cytokines and vascular-related molecules by tumo 2005 Nov OBJECTIVE: Analysis of serum concentrations and modifications of tumor necrosis factor-a (TNF-a), its soluble receptors (TNFR), interleukin 10 (IL-10), and vascular related molecules [soluble vascular cell adhesion molecule 1 (sVCAM-1), vascular endothelial growth factor (VEGF)] after therapy with methotrexate (MTX) and anti-TNF (infliximab) in patients with rheumatoid arthritis (RA). METHODS: Thirty-six patients with RA and 20 healthy controls were included. Patients had been orally taking a stable dose of MTX of at least 12.5 mg/week for a minimum of 6 months before inclusion in the study. Twenty-five patients had shown a clinical response to MTX (MTX Group). The other 11 had shown an unsatisfactory response and presented with active RA; they were selected for additional treatment with infliximab (MTX + IFM Group). Disease activity score (DAS28), hemoglobin concentration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum levels of TNF-a, soluble TNFR, IL-10, sVCAM-1 and VEGF were determined at baseline and prior to every infusion of infliximab (3 mg/kg) at 2, 6, 14, 22, and 30 weeks. RESULTS: Although serum levels of TNF-a were similar in patients and controls, patients showed significantly higher concentrations of both soluble TNFR (sTNFR55 and sTNFR75), IL-10, sVCAM-1, and VEGF than healthy individuals. Significantly higher levels of sVCAM-1 and VEGF, but not of the other tested molecules, were detected in those with active disease. After infliximab treatment (MTX + IFM Group) there was a significant decrease in DAS28 and modified Health Assessment Questionnaire scores and ESR and CRP levels. Serum concentration of VEGF showed a significant decrease after infliximab, with levels comparable to those of patients with inactive RA, although VEGF continued to present higher values than in healthy controls. CONCLUSION: Increased levels of vascular related molecules sVCAM-1 and VEGF are serum markers of active RA. The absence of normalization of levels of these molecules in patients with inactive RA could be one of the reasons response to therapy is only temporary.
16172183 Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile 2005 Oct Drugs prescribed for rheumatoid arthritis are often associated with gastrointestinal toxicity, and proton pump inhibitors may be coadministered for gastroprotection. In this open-label study, the effect of lansoprazole 30 mg qd and naproxen 500 mg bid on the pharmacokinetic profile of methotrexate was investigated. Twenty-seven adult rheumatoid arthritis patients on stable oral methotrexate doses (7.5-15 mg/week) for a minimum of 3 months were enrolled. Methotrexate pharmacokinetics were assessed on days -1 (methotrexate alone) and 7 (methotrexate with lansoprazole and naproxen). Pharmacokinetics of methotrexate and 7-hydroxymethotrexate were not altered by coadministration of methotrexate with lansoprazole and naproxen; point estimates and 90% confidence intervals for the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries. Therefore, coadministration of naproxen and lansoprazole for 7 days does not affect the pharmacokinetic profile of low doses of methotrexate.
16634363 The world of biologics. 2006 In March 2002 the National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of anti-TNF therapy for patients with rheumatoid arthritis (RA). The guidelines recommended that all RA patients treated with these drugs should be enrolled on a national register which had been established by the British Society for Rheumatology (the BSRBR). A comparison cohort of RA patients treated with traditional disease modifying drugs (DMARDs) is also being recruited. The main role of the BSRBR is to study the long-term safety of biologic drugs. Up to the end of March 2005, 9508 patients with RA had been enrolled on the BSRBR. Four thousand, three-hundred and six had been treated with etanercept, 3561 with infliximab, 1500 with adalimumab and 141 with anakinra. With regards to anti-TNF drugs, 79% remained on their original drug at six months, 65% of whom could be classified as responders. Co-prescription with methotrexate was associated with a 70% response rate. Patients with a high baseline level of disability were less likely to respond. Overall the rates of serious infection were not increased in the anti-TNF versus the comparison cohort. However the rates of skin and soft tissue infection and of intracellular infections (eg, salmonella, listeria, legionella) were increased. There were 11 cases of tuberculosis (seven extra-pulmonary). There was concern about the high mortality rates among patients with baseline pulmonary fibrosis treated with anti-TNF therapy. It is unclear whether this is related to the drug or to the underlying disease. The rates of malignancy and mortality were not increased compared to the DMARD treated group in the short term. Further follow-up is needed to determine the long term safety of these drugs.
15880810 A 48-week, randomized, double-blind, double-observer, placebo-controlled multicenter trial 2005 May OBJECTIVE: To evaluate the efficacy and safety of adding intramuscular (IM) gold to the treatment regimen of patients with rheumatoid arthritis (RA) who have a suboptimal response to methotrexate (MTX). METHODS: A randomized, double-blind, double-observer, placebo-controlled multicenter trial of 48 weeks was conducted. Sixty-five RA patients who had a suboptimal response to >/=12 weeks of MTX therapy were randomly assigned to receive weekly IM gold or placebo in addition to MTX. Gold was administered according to a standard protocol developed for the study. The primary outcome measure was the percentage of patients who met the American College of Rheumatology (ACR) 20% improvement criteria (achieved an ACR20 response) at week 48. Secondary outcomes included the percentages of patients achieving ACR50 and ACR70 responses, the individual criteria that make up the primary outcome, quality of life, direct and indirect health care costs, intraarticular steroid use, and adverse events, among other measures. Statistical analyses were based on an intent-to-treat strategy. RESULTS: Sixty-one percent of patients receiving gold achieved an ACR20 response compared with 30% of patients receiving placebo (chi(2) = 6.04, P = 0.014; logistic regression odds ratio 3.64 [95% confidence interval 1.3, 10.4], P = 0.016). Twenty-six percent of patients receiving gold achieved an ACR50 response compared with 4% of patients receiving placebo (P = 0.017), and 21% of patients receiving gold achieved an ACR70 response compared with 0% of patients receiving placebo (P = 0.011). From both clinical and cost-effectiveness perspectives, gold was the preferred and dominant strategy. Study treatment was discontinued in 23 patients (14 in the placebo group compared with 9 in the gold group; P = 0.022) due to loss to followup, adverse events, or lack of efficacy. CONCLUSION: In RA patients with a suboptimal response to MTX, adding weekly IM gold causes significant clinical improvement. Adverse events were minor, and IM gold-related adverse events led to discontinuation in only 11% of the gold group over 48 weeks.
16636937 Low-dose methotrexate-induced pancytopenia. 2007 Jan Methotrexate (MTX) has gained wide acceptance among both patients and rheumatologists due to its efficacy and safe therapeutic window in a variety of inflammatory rheumatological disorders. However, it has the potential to cause serious, life-threatening complications and even mortality. In the present series, we have reviewed our data of five patients who developed serious pancytopenia after the use of MTX, including one who died. Two of these resulted from prescription errors by primary care physicians. The clinical, laboratory, and outcome profile of all five cases are discussed with a brief review of the literature about MTX-induced pancytopenia. There is an urgent need to increase awareness in primary care physicians, patients, and pharmacists toward informed prescribing, dispensing, and monitoring of MTX to prevent such mishaps in the future.
17150160 Application of surface roughness analysis on micro-computed tomographic images of bone ero 2006 Oct Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments. This study introduces a three-dimensional method for bone surface roughness measurement from micro-computed tomographic data obtained from rats subjected to collagen-induced arthritis (CIA), in which the degree of bone erosion is related to the severity and the duration of the disease. In two studies of rat CIA, the surface roughness of the talus bone following 21 days of disease increased 559% and 486% from the control group. At 41 days following disease induction, the roughness of the bone surface increased 857% above baseline. The roughness of the control samples was similar from each study (less than 4% different), demonstrating the robustness of the algorithm. Treatment with methotrexate at 0.1 mg/kg daily demonstrated significant protection from bone erosion, whereas the 0.05 mg/kg daily dose was not efficacious (98% versus 22% inhibition of roughness-measured bone erosion). The main advantage of such an algorithm is demonstrated in the preclinical drug study of rat CIA with methotrexate treatment, indicating the immediate utility of this approach in drug development studies.
17049139 A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the 2006 Nov OBJECTIVES: This report reviews the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and infliximab, agents that inhibit tumour necrosis factor-alpha (TNF-alpha), when used in the treatment of rheumatoid arthritis (RA) in adults. DATA SOURCES: Electronic databases were searched up to February 2005. REVIEW METHODS: Systematic reviews of the literature on effectiveness and cost-effectiveness were undertaken and industry submissions to the National Institute for Health and Clinical Excellence (NICE) were reviewed. Meta-analyses of effectiveness data were also undertaken for each agent. The Birmingham Rheumatoid Arthritis Model (BRAM), a simulation model, was further developed and used to produce an incremental cost-effectiveness analysis. RESULTS: Twenty-nine randomised controlled trials (RCTs), most of high quality, were included. The only head-to-head comparisons were against methotrexate. For patients with short disease duration (
16960243 Medical therapy: where are we now? 2006 Sep 15 PURPOSE: This article reviews the mechanisms of action, safety, and efficacy of the nonbiologic, or traditional, disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine. It also addresses various aspects of rheumatoid arthritis (RA) clinical trials that warrant careful interpretation, including response criteria, outcomes measurements, study designs, and results of combination therapy trials. SUMMARY: The considerable progress in the treatment of RA over the past 20 years is due in large part to a better understanding of how to use DMARDs optimally and the introduction of biologic agents. In addition to their ability to suppress inflammation, and thereby reduce symptoms of pain and stiffness, these drugs also have the potential to alter the course of RA by slowing disease progression and reducing joint damage. CONCLUSION: Studies have demonstrated that early treatment of RA and rapid suppression of inflammation are extremely important as they provide long-term benefits and improve the overall prognosis for patients with the disease.
16645967 Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone co 2006 May OBJECTIVE: To investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect. METHODS: Patients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo-cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo-cyclosporine dosage up to 4 mg/kg. RESULTS: At 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR-N) in the 2 groups was 80.0% (interquartile range 40.1-91.8%) and 54.5% (interquartile range 2.4-87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was -0.2 +/- 6.5 and 0.4 +/- 6.9 (mean +/- SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group. CONCLUSION: Combined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR-N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups.
16882589 The effect of methotrexate (MTX) on expression of signalling lymphocytic activation molecu 2006 Jul OBJECTIVE: To investigate the effect of methotrexate (MTX) on cytokine production by activated CD4+ T-cells in patients with rheumatoid arthritis (RA). METHODS: The effect of MTX on intracellular expression of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), and cell surface expression of signalling lymphocytic activation molecule (SLAM) from freshly isolated peripheral blood mononuclear cells (PBMCs), and after in vitro culture with or without MTX, was analysed with flow cytometry in 18 patients with RA and 20 healthy controls. RESULTS: Intracellular expression of IFN-gamma and IL-4 on freshly isolated CD4+ T-cells was significantly higher in patients with RA than in the controls (p<0.05). Intracellular expression of both IFN-gamma and IL-4 after culture with MTX was significantly lower than those after culture without MTX in patients with RA. Although no significant difference was observed in SLAM expression on freshly isolated CD4+ T-cells between patients with RA and the controls, MTX significantly decreased SLAM expression on both activated IFN-gamma+ and IL-4+CD4+ T-cells in patients with RA. CONCLUSION: In vitro modulation of the cytokine network by MTX, IFN-gamma, and IL-4 is one of the major targets for MTX, and production of IFN-gamma and IL-4 by PBMCs may be suppressed by SLAM on activated CD4+ T-cell in patients with RA.
16385351 [Biologic therapy with anti-TNFα in rheumathoid arthritis]. 2005 OBJECTIVE: To evaluate the efficacy, the tolerability, and treatment survival of the association of anti-TNFα (Infliximab, Etanercept, Adalimumab) plus Methotrexate vs Methotrexate as monotherapy in patients with reumathoid arthritis (RA). METHODS: Review of published controlled randomized clinical studies on the association of anti-TNFα plus Methotrexate vs Methotrexate alone in patients with rheumathoid arthritis (RA). Results in terms of remission and progression of radiologic damage, and clinical response expressed in terms of ACR 50 or ACR 70 were reviewed in the different studies. RESULTS: In patients with RA the association of anti-TNFα plus Methotrexate led to a greater remission of radiologic damage and marked improvement of clinical response expressed as ACR 50 or ACR 70 compared to therapy with Methotrexate only. CONCLUSIONS: In the absence of controlled studies, review of the published studies showed that in RA patients the association of anti-TNFα plus Methotrexate is extremely more efficacious than therapy with Methotrexate only. Choice of the drug depends on the activity of the disease, the necessity of a fast response, the presence of side effects, the schedule of treatment and consequently the direct and indirect costs of the drug, and the easiness on supply and distribution.
15934109 Impact of managed care on the use of biologic agents for rheumatoid arthritis. 2005 Jun 15 OBJECTIVE: To compare the use of biologic agents among persons with rheumatoid arthritis (RA) in managed care and fee-for-service settings. METHODS: The present study uses data from the University of California, San Francisco RA Panel Study in which 529 patients with RA from a random sample of northern California rheumatologists were interviewed annually between 1999 and 2002 using a structured survey instrument. Linear and logistic regression were used to compare current utilization, initiation, and cessation of biologic agents and other treatments among patients with RA in managed care and fee-for-service settings, with and without adjustment for differences in demographic and health characteristics. RESULTS: After adjustment, patients with RA in health maintenance organizations (HMOs) were significantly less likely to use biologic agents than those in other managed care settings (difference of -6.6%; 95% confidence interval [95% CI] -11.4%, -1.7%) or than those in fee-for-service settings (difference of -12.5%; 95% CI -19.0%, -5.9%); patients in other managed care settings and fee-for-service did not differ significantly in their use of biologic agents. Patients with RA in HMOs were significantly less likely than those in other managed care settings to initiate the use of biologic agents (difference of -7.3%; 95% CI -11.5%, -3.1%); there were no other differences between patients in HMOs and those in other managed care and fee-for-service settings in rates of initiation or cessation of these agents. Patients with RA in HMOs were less likely to use methotrexate, cyclooxygenase 2 (COX-2) inhibitors, and corticosteroids than those in other managed care settings; they were also less likely to use COX-2 inhibitors than those in fee-for-service settings. CONCLUSION: Patients with RA in HMOs were significantly less likely to use biologic agents than those in other managed care and fee-for-service settings, primarily due to lower rates of initiation.
16079172 Patient reported outcomes in a trial of combination therapy with etanercept and methotrexa 2006 Mar OBJECTIVE: To compare patient reported measures of function, health related quality of life (QoL), and satisfaction with medication among patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), etanercept, or both for up to 1 year. METHODS: In a 52 week, double blind, clinical trial, patients with active RA were randomised to receive etanercept 25 mg twice weekly, methotrexate up to 20 mg weekly, or combination therapy. The Health Assessment Questionnaire (HAQ) disability index, EuroQoL health status visual analogue scale (EQ-5D VAS), patient global assessment, and patient general health VAS were administered at baseline and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52. Satisfaction with the medication was compared at 52 weeks. RESULTS: Of 682 enrolled patients, 522 completed 52 weeks of treatment. Mean improvement from baseline in HAQ score was 0.65, 0.70, and 1.0 for MTX, etanercept, and the combination, respectively. The mean percentage and absolute improvement in the HAQ was significantly higher (p<0.01) for combination therapy than for either of the monotherapies. Combination therapy produced significantly more rapid achievement of HAQ < or =0.5 sustained for 6 months than either of the monotherapies (p<0.01). Compared with patients receiving monotherapy, those receiving combination therapy achieved a significantly better (p<0.05) health state as measured by the EQ-5D VAS (mean (SD) 63.7 (3.2), 66.8 (3.2), 72.7 (3.1) for MTX, etanercept, and the combination, respectively). Results were similar for other assessments (p<0.01). Patients in combination and etanercept groups were significantly more likely (p<0.0001, p = 0.0009, respectively) to report satisfaction with the medication. CONCLUSIONS: Combination therapy with etanercept and methotrexate improved function, QoL, and satisfaction with the medication significantly more than monotherapy.
16436036 Anti-TNF-alpha agents in the treatment of psoriatic arthritis. 2006 Feb Psoriatic arthritis (PsA) is a potentially debilitating disease that may affect small and large peripheral joints, entheses and the axial skeleton. The different clinical manifestations of PsA have been accounted for by various proposals of subdividing the patients into different subgroups. According to the predominant clinical symptoms, most patients can be classified as belonging to the spectrum of spondyloarthritides (SpA) or rheumatoid arthritis (RA). The conventional therapeutic approach comprises non-steroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids, and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate, ciclosporin and leflunomide. Similar to RA, recent trials in PsA have shown excellent results with the tumour necrosis factor (TNF) blockers etanercept, infliximab and adalimumab, which have positive effects not only on joints, but also on the skin when affected by psoriasis, quality of life, function and slowing of disease progress, as evidenced radiologically. Anti-TNF therapy has been generally safe in clinical trials of PsA. Taken together, there has been definite recent progress in the treatment of PsA, especially for severely affected patients.
16641042 Drug survival and reasons for discontinuation of intramuscular methotrexate: a study of 21 2006 Mar OBJECTIVES: To assess the drug survival and reasons for discontinuation of intramuscular methotrexate (imMTX) in rheumatological patients who had switched to imMTX from oral methotrexate (oMTX). METHODS: Data from 212 consecutive patients who switched from oMTX to imMTX therapy at our outpatient clinic between April 1997 and January 2004 were collected retrospectively through survey of case records. Data included reason for discontinuation of oMTX, disease activity parameters, duration of imMTX therapy, and, in patients who withdrew, the reason for discontinuation of imMTX. RESULTS: The main reasons for switching from oMTX to imMTX were lack of efficacy (66%) and adverse events (28%). After 6 months, 114 patients (54%) were still receiving imMTX therapy, and their median serum C-reactive protein (CRP) and the percentage of patients who had received glucocorticoids during the previous 6 weeks had decreased (p<0.001). The median survival of imMTX therapy was 7.5 months (interquartile range 3-17). Twenty per cent of the patients received imMTX for more than 24 months. Of the 212 patients, 41% and 9% stopped imMTX therapy because of lack of efficacy and adverse events, respectively. Of the patients who had stopped oMTX because of adverse events, 22% also withdrew from imMTX because of adverse events. CONCLUSION: Half of the patients benefited from switching from oral to intramuscular methotrexate for at least 6 months, but only a minority adhered to the treatment for years. Lack of efficacy was the most frequent reason for discontinuation, while adverse events were rare.
16308341 Long term efficacy and safety of adalimumab plus methotrexate in patients with rheumatoid 2006 Jun OBJECTIVE: To evaluate the efficacy and safety of adalimumab plus methotrexate (MTX) given for up to 4 years in patients with active, longstanding rheumatoid arthritis. METHODS: Patients responding inadequately to MTX were entered into a 24 week, controlled study (ARMADA) with adalimumab plus MTX or placebo plus MTX, and some were enrolled in a subsequent open label extension. The efficacy and safety of treatment were evaluated. Additional analyses were made for those patients whose corticosteroid and/or MTX dosages were adjusted during the extension. RESULTS: Of 271 patients in the original ARMADA trial, 262 received at least one dose of adalimumab and were evaluated. At the time of analysis, 162/262 (62%) patients had remained in the study and received treatment for a mean of 3.4 years. Withdrawals were for lack of efficacy (8%), adverse events (12%), and other reasons (18%). In 147 patients who completed 4 years' treatment, efficacy achieved at 6 months was maintained. At 4 years, 78%, 57%, and 31% had achieved ACR20/50/70; 43% achieved clinical remission (DAS28 <2.6); and 22% had no physical function abnormalities (HAQ = 0). Results were similar for 196 patients who received treatment for 2-4 years. Efficacy was maintained in many patients when dosages were decreased (corticosteroids (51/81 (63%) patients), MTX (92/217 (42%)), or both (25/217 (12%))). Serious adverse events were comparable during open label treatment and the controlled phase. Serious infections occurring during open label treatment and the blinded period were similar (2.03 v 2.30 events per 100 patient-years, respectively). CONCLUSIONS: Adalimumab plus MTX sustained clinical response and remission in patients with RA during 4 years. The safety profile during the first 6 months was similar to that after 4 years' follow up. Reduction of corticosteroid and/or MTX dosages did not adversely affect long term efficacy.
16705046 Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: 2006 Dec BACKGROUND: Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted. OBJECTIVE: To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA. METHODS: The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression. RESULTS: 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission. CONCLUSIONS: These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.
16997599 Use of tumor necrosis factor inhibitors in rheumatoid arthritis: a national survey of prac 2006 Dec OBJECTIVES: To determine the prescribing practices, laboratory monitoring protocols, and perceived barriers of United States rheumatologists in prescribing tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA). METHODS: A survey questionnaire was mailed to 1970 rheumatologists who were randomly selected from a national sample of 3008 rheumatologists. A one-page non-response questionnaire was mailed to approximately 200 randomly selected non-responding rheumatologists to assess non-response bias. RESULTS: Two mailings yielded a response rate of 22.3% (428 completed, usable surveys out of 1922 deliverable surveys). Rheumatologists reported using all three agents in patients with moderate RA (82-87%), severe RA (94-96%), and in newly diagnosed and mild RA patients (10-18%). In patients with severe RA who inadequately responded to methotrexate, 91% of rheumatologists reported using a TNF inhibitor with one other disease modifying anti-rheumatic drug. Over 94% of rheumatologists reported switching patients from one TNF inhibitor to a different TNF inhibitor due to inadequate response or side effects. Most rheumatologists (96%) ordered the purified protein derivative test for tuberculosis, with almost 82% conducting this test at baseline. Costs to patients and insurance coverage were perceived as major barriers to prescribing these agents although the perception was slightly lower with infliximab than with adalimumab or etanercept. CONCLUSIONS: The use of TNF inhibitors is not restricted to patients with moderate and severe RA. Rheumatologists are fairly similar in their utilization of the three TNF inhibitors although some variation exists in terms of laboratory practices and perceived barriers regarding the use of these agents.
16874796 Antirheumatic drug use and the risk of acute myocardial infarction. 2006 Aug 15 OBJECTIVE: To assess the risk of acute myocardial infarction (AMI) associated with the use of disease-modifying antirheumatic drugs (DMARDs) and other medications commonly used in rheumatoid arthritis (RA). METHODS: We conducted a nested case-control analysis within a cohort of subjects with RA, observed between 1999 and 2003, identified from the PharMetrics claims database. For each first AMI hospitalization identified during followup, 10 controls matched on sex, age, and time of study entry were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of AMI associated with the current use of anti-RA therapy, as measured from dispensed prescriptions, after adjustment for AMI risk factors. RESULTS: The cohort included 107,908 subjects (average age 54 years at cohort entry). During followup, 558 AMI cases occurred (3.4 per 1,000 per year). AMI rate was significantly decreased with the current use of any DMARD (adjusted RR 0.80, 95% confidence interval [95% CI] 0.65-0.98). This effect was consistent across all DMARDs, including methotrexate (RR 0.81, 95% CI 0.60-1.08), leflunomide (RR 0.28, 95% CI 0.12-0.65), and other traditional DMARDs (RR 0.67, 95% CI 0.46-0.97), but not biologic agents (RR 1.30, 95% CI 0.92-1.83). AMI rate increased with the use of glucocorticoids (RR 1.32, 95% CI 1.02-1.72) but not with nonselective nonsteroidal antiinflammatory drugs (RR 1.05, 95% CI 0.81-1.36) or cyclooxygenase 2 (COX-2) inhibitors (RR 1.11, 95% CI 0.87-1.43). CONCLUSION: DMARD use is associated with a reduction in AMI risk in patients with RA. No risk increase was found with the COX-2 inhibitors in this population.