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ID PMID Title PublicationDate abstract
11857432 In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed fo 2002 May Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage.
15188329 Cardiovascular care and cancer screening in female nurses with and without rheumatoid arth 2004 Jun 15 OBJECTIVE: To compare frequencies of cancer screening and cardiovascular treatments aimed at reducing acute myocardial infarction in women with and without rheumatoid arthritis (RA). METHODS: Data from the prospective Nurses' Health Study were analyzed for the 491 women diagnosed with RA prior to 1998 and the 82,884 women without RA. Cardiovascular treatments included aspirin use, treatment with a cholesterol-lowering agent, cardiac catheterization, and coronary artery revascularization; cancer screening consisted of mammography and bimanual pelvic examinations. Adjustments were made for potential confounders using multivariate logistic regression. RESULTS: After adjusting for cardiovascular risk factors, use of nonsteroidal antiinflammatory drugs, and a history of gastric or duodenal ulcer, women with RA and no history of cardiac disease were 35% less likely to report taking aspirin regularly (odds ratio [OR] 0.65, 95% confidence interval [95% CI] 0.51-0.84). The use of cholesterol-lowering treatment, angiography, and revascularization was not statistically different in women with and without RA. After adjusting for cancer risk factors, there appeared to be an increased likelihood of mammography in women with RA compared with those without RA (OR 1.41, 95% CI 0.97-2.04), although this result was not statistically significant. Bimanual pelvic examination was reported with similar frequency between the 2 groups. CONCLUSION: Other than aspirin use, care to prevent acute myocardial infarction and cancer screening practices were similar among women with RA compared with women without RA.
12355475 Frequency of infection in patients with rheumatoid arthritis compared with controls: a pop 2002 Sep OBJECTIVE: A high frequency of infections complicating rheumatoid arthritis (RA) has been described in reports of case series. This retrospective longitudinal cohort study was undertaken to compare the frequency of infections in a population-based incidence cohort of RA patients with that in a group of individuals without RA from the same population. METHODS: RA patients included all members of an incidence cohort of Rochester, Minnesota residents ages >or=18 years who were first diagnosed as having RA between 1955 and 1994. One age- and sex-matched subject without RA was selected for each patient with RA. Study subjects were followed up by review of their entire medical record until death, migration from the area, or study end (January 1, 2000), and details of all documented infections, along with information on potential risk factors for infection, were recorded. Hazard ratios for infections were estimated using stratified Andersen-Gill proportional hazards models, with adjustment for potential confounders. RESULTS: The 609 RA patients and 609 non-RA study subjects (mean age 58.0 years; 73.1% female) were followed up for a mean of 12.7 years and 15.0 years, respectively, reflecting higher mortality among the group with RA. Hazards ratios for objectively confirmed infections, infections requiring hospitalization, and any documented infection in patients with RA were 1.70 (95% confidence interval [95% CI] 1.42-2.03), 1.83 (95% CI 1.52-2.21), and 1.45 (95% CI 1.29-1.64), respectively, after adjustment for age, sex, smoking status, leukopenia, corticosteroid use, and diabetes mellitus. Sites of infection with the highest risk ratios were bone, joints, skin, soft tissues, and the respiratory tract. CONCLUSION: In this study, patients with RA were at increased risk of developing infections compared with non-RA subjects. This may be due to immunomodulatory effects of RA, or to agents with immunosuppressive effects used in its treatment.
15829424 Leflunomide reduces nitric oxide production in patients with active rheumatoid arthritis. 2005 Jun OBJECTIVES: Leflunomide is an immunomodulatory agent that was recently approved for the treatment of rheumatoid arthritis (RA). The mechanism of action is not fully understood. Nitric oxide (NO) plays an important role in the pathogenesis of RA. Leflunomide has been shown to cause cell specific inhibition of inducible nitric oxide synthase (iNOS) activation in animal models. We carried out this study to determine if there was alteration in NO production in patients with RA. METHODS: An 8-week open label study was carried out on patients with adult onset active RA. We measured levels of nitrite and citrulline spectrophotometrically as surrogate markers of NO production. Within-patient serum levels of nitrite and citrulline were compared with leflunomide therapy at three points of time (at 0, 4 and 8 weeks of therapy). RESULTS: Thirty-three patients with active RA were enrolled for this study. These patients were a subset of 63 individuals who are studied for clinical efficacy of leflunomide. Three patients were lost to follow-up. Median nitrite levels were 817.2 (nmol/ml) at the start of therapy and this declined to 440.9 nmol/ml and 301.1 nmol/ml at 4 and 8 weeks of therapy. Median citrulline levels were 649.3 nmol/ml at the start of the study, which declined to 549.2 nmol/ml and 485.4 nmol/ml at 4 and 8 weeks, respectively. Statistically significant decrease in median values for serum nitrite and citrulline levels was documented after 4 weeks of leflunomide therapy (p<0.01), which was sustained at 8 weeks (p<0.01), although there was no further fall between 4 and 8 weeks (p>0.1). CONCLUSIONS: Leflunomide inhibits nitric oxide production in patients with active RA. Inhibition of NO synthesis may be one of the mechanisms responsible for the immunomodulatory activity of leflunomide.
12407800 [Chloroquine cardiomyopathy revealed by complete atrio-ventricular block. A case report]. 2002 Sep We describe a rare case of chloroquine cardiomyopathy occurring during long term (7 years) treatment for rheumatoid polyarthritis in a 42 year old woman. There was an isolated acute severe conduction defect, which is particularly rare. Histological study with the electron microscope allowed confirmation of this diagnosis. We report here the secondary cardiological effects of this frequently used synthetic antimalarial.
12860733 Long term structural effects of combination therapy in patients with early rheumatoid arth 2003 Aug OBJECTIVE: To evaluate whether early combined therapy with methotrexate (MTX) and sulfasalazine (SSZ) during the first year in early rheumatoid arthritis (RA) induces long term beneficial effects, compared with monotherapy, when the further treatment strategy is a free choice. STUDY DESIGN: five year multicentre prospective longitudinal trial. PARTICIPANTS: 146/205 patients with RA previously included in a one year prospective randomised trial comparing the effects of treatment with MTX, SSZ, or a combination of both. Criteria for inclusion: patients with early RA (< or =1 year duration). Follow up: between the end of years 1 and 5, patients were followed up and treated by their own rheumatologist, who was allowed to indicate any treatment. OUTCOME MEASURES: disease activity score (DAS), health assessment questionnaire (HAQ), and Sharp/van der Heijde radiological score at baseline and after five years of follow up. ANALYSIS: comparison of the five year follow up DAS, HAQ, and radiological scores in patients given combined and single treatment during the first year. RESULTS: At the end of the five years of follow up, the patients primarily receiving single or combined treatment had similar mean DAS, HAQ, and radiographic scores. CONCLUSION: Treatment of patients with early RA using combined therapy with MTX and SSZ during the first year did not influence the long term inflammatory status, or disability, or structural changes, compared with single disease modifying antirheumatic drug treatment.
12787511 Assessment of pain in patients with rheumatic diseases. 2003 Jun Pain is the most prominent symptom in people with musculoskeletal disorders and the most common reason for patients to seek medical help. However, pain generally is not recorded quantitatively in usual medical care. A quantitative measure of pain is not needed in acute medical care but is essential over long periods as patients and health professionals cannot gauge accurately changes in levels of pain over years. The experience of pain is subjective, and early efforts by health professionals to estimate pain through an 'objective' measure of pain status were useful in clinical research but not in clinical care. Over the last three decades, self-report questionnaires have been developed in which a patient may record quantitatively a pain score, as well as other data concerning clinical status, which may be repeated over time to discern whether patients are improved, similar or worse. The most robust quantitative pain measure appears to be a simple 10-cm visual analogue scale (VAS) which can be completed by the patient and scored by a health professional in less than 30 s. These data cannot be obtained from any source other than the patient. Pain scores are correlated with 'objective' measures such as radiographs, laboratory tests and physical examination findings, but more strongly correlated with scores for functional status and psychological distress in patients with rheumatic diseases. It is recommended that quantitative assessment of pain be included at each visit in routine rheumatology care, along with assessment of functional disability, global status and other patient variables, using a patient self-report questionnaire to improve patient care.
15286007 Effect of treatment of rheumatoid arthritis with infliximab on IFN gamma, IL4, T-bet, and 2005 Mar OBJECTIVE: To study interferon gamma (IFN gamma) production and the expression of T-bet and GATA-3, the transcription factors associated with Th1 and Th2, in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis before and during infliximab treatment, so as to distinguish between a disease specific and a disease activity dependent defect. METHODS: Rheumatoid PBMC were obtained at weeks 0 and 6 of infliximab treatment and cultured for seven days with or without interleukin (IL)12 or the combination of IL12 and IL18. IFN gamma concentrations in supernatants were determined by ELISA. mRNA expression of IFN gamma, IL4, T-bet, and GATA-3 was determined by real time RT-PCR in whole blood at weeks 0 and 22. RESULTS: A reduction in spontaneous IFN gamma production and in the response to Th1 inducing cytokines occurred in rheumatoid PBMC. Reduction of systemic inflammation with infliximab treatment increased IFN gamma production in response to IL12 or IL12+IL18. The IFN gamma/IL4 expression ratio of rheumatoid blood before treatment was lower than in healthy controls but was increased by infliximab treatment. T-bet expression or T-bet/GATA-3 ratio of rheumatoid blood was less than in controls. The T-bet/GATA-3 ratio was not influenced by infliximab treatment. CONCLUSIONS: Regulation of T-bet and GATA-3 or IFN gamma and IL4 expression appeared different. The IFN gamma/IL4 ratio might express the blood Th1/Th2 balance better than the T-bet/GATA-3 ratio. Reduced IFN gamma production by rheumatoid PBMC and levels of IFN gamma and IL4 mRNA expression in blood were linked to disease improvement, indicating an association between this systemic Th1 feature and disease activity.
15322813 Pulmonary abscess due to leflunomide use in rheumatoid arthritis: a case report. 2005 Mar A 43-year-old woman had rheumatoid arthritis (RA) for 5 years and complained of fever, arthralgia/myalgia, and night sweating for a month. She had been receiving only leflunomide (20 mg/day) for 5 months. On admission, there was no evidence of active arthritis or vasculitic lesion. Laboratory evaluation showed an erythrocyte sedimentation rate of 145 mm/h and C-reactive protein of 160 mg/dl. All cultures were negative. Chest radiograph and computed tomography (CT) revealed a pulmonary abscess. Staphylococcus aureus multiplied in the culture of a purulent sample obtained from the abscess under ultrasonography. The leflunomide was stopped, and sultamicillin (IV 4x2 g/day) was started for a further 6 weeks. Four weeks later, the patient had completely recovered and CT showed significant improvement of the pulmonary abscess. Ten milligrams/day of prednisolone and 7.5 mg/week of methotrexate were started for RA treatment. The patient has been under control for 5 months without any further abscess or RA activation.
14676136 Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid 2003 Dec 16 There is intense interest in mechanisms whereby low-grade inflammation could interact with conventional and novel vascular risk factors to promote the atheromatous lesion. Patients with rheumatoid arthritis (RA), who by definition manifest persistent high levels of inflammation, are at greater risk of developing cardiovascular disease. Mechanisms mediating this enhanced risk are ill defined. On the basis of available evidence, we argue here that the systemic inflammatory response in RA is critical to accelerated atherogenesis operating via accentuation of established and novel risk factor pathways. By implication, long-term suppression of the systemic inflammatory response in RA should be effective in reducing risk of coronary heart disease. Early epidemiological observational and clinical studies are commensurate with this hypothesis. By contrast, risk factor modulation with conventional agents, such as statins, may provide unpredictable clinical benefit in the context of uncontrolled systemic inflammatory parameters. Unraveling such complex relationships in which exaggerated inflammation-risk factor interactions are prevalent may elicit novel insights to effector mechanisms in vascular disease generally.
12928381 Allele-specific expression of the IL-1 alpha gene in human CD4+ T cell clones. 2003 Sep 1 A number of reports have described the monoallelic expression of murine cytokine genes. Here we describe the monoallelic expression of the human IL-1alpha gene in CD4+ T cells. Analysis of peripheral blood T cell clones derived from healthy individuals revealed that the IL-1alpha gene shows predominantly monoallelic expression. Monoallelic expression was observed in Th0, Th1, and Th2 cell clones. In addition, we demonstrate monoallelic expression in T cell clones from rheumatoid arthritis patients derived from synovial fluid of the knee joint, suggesting that the occurrence of this phenomenon is not different from that in clones derived from healthy individuals. The finding of monoallelic expression of a cytokine gene in human CD4+ T cell clones provides evidence for allele-specific silencing/activation as another layer of regulation of IL-1alpha gene expression.
14560420 Thirteen year results of total hip arthroplasty using a tapered titanium femoral component 2003 Oct Although cementless arthroplasty with a tapered titanium femoral component has proven reliable in young patients with excellent bone quality, studies involving patients with poor bone quality are lacking. The present study evaluates the results of total hip arthroplasty (THA) using such a femoral component in patients with Type C femoral bone. Ninety-two THAs were performed in 81 patients aged 65 years and older using a tapered titanium cementless femoral component. Follow-up in 62 patients (72 hips) averaged 13.2 years (minimum, 10 years); 19 patients were lost to follow-up. According to Door's criteria, 20 femora were classified as Type A, 19 as Type B, and 33 as Type C. No stem was revised because of stem instability, thigh pain, or osteolysis. One stem was removed because of sepsis. Six acetabula were revised because of polyethylene wear and periacetabular osteolysis. Four patients reported mild thigh pain. Radiologic signs of osseous integration for cylindrical extensively porous coated cobalt-chrome femoral components are not valid for tapered titanium designs.
15249666 A methionine aminopeptidase-2 inhibitor, PPI-2458, for the treatment of rheumatoid arthrit 2004 Jul 20 The hallmark of rheumatoid arthritis (RA) is the progressive destruction of articular joints, characterized by invasive synovial hyperplasia and pathological neovascularization. Here we report that PPI-2458, a member of the fumagillin class of irreversible methionine aminopeptidase-2 (MetAP-2) inhibitors, potently inhibits the proliferation of human fibroblast-like synoviocytes (HFLS-RA), derived from RA patients, with a growth inhibitory concentration 50 (GI(50)) of 0.04 nM and a maximum inhibition of >95% at 1 nM. Human umbilical vein endothelial cells (HUVEC) are similarly inhibited in proliferation by PPI-2458 (GI(50), 0.2 nM). We developed a method to measure the level of MetAP-2 enzyme inhibition after exposure to PPI-2458 and demonstrate that growth inhibition of PPI-2458-sensitive HFLS-RA and HUVEC is linked to MetAP-2 enzyme inhibition, in a dose-dependent fashion. The secretion of several inflammatory mediators such as IL-6 and vascular endothelial growth factor from activated HFLS-RA was not inhibited by PPI-2458. The CNS toxicity profile of PPI-2458, determined by the incidence of seizures, is significantly improved over that of the parental compound TNP-470. In the rat model of peptidoglycan-polysaccharide-induced arthritis, PPI-2458 significantly attenuated paw swelling when therapeutically administered after the onset of chronic disease. We suggest that the mechanism of PPI-2458 action, highly selective and potent anti-proliferative activity on HFLS-RA and HUVEC in vitro, a significantly improved CNS toxicity profile, and marked attenuation of chronic disease in the rat peptidoglycan-polysaccharide arthritis model in vivo, positions this compound as a drug for the treatment of RA.
12010573 Highly efficient genetic transduction of primary human synoviocytes with concentrated retr 2002 We are developing retroviral-mediated gene transfer to human fibroblast-like synovial cells (FLS) as one approach to characterizing genetic pathways involved in synoviocyte pathophysiology. Prior work has suggested that FLS are relatively refractory to infection by Moloney murine leukemia virus based vectors. To determine if viral titer influenced the transduction efficiency of FLS, we optimized a rapid, efficient, and inexpensive centrifugation method to concentrate recombinant retroviral supernatant. The technique was evaluated by measurement of the expression of a viral enhanced green fluorescent protein transgene in transduced cells, and by analysis of viral RNA in retroviral supernatant. Concentration (100-fold) was achieved by centrifugation of viral supernatant for four hours, with 100% recovery of viral particles. The transduction of FLS increased from approximately 15% with unconcentrated supernatant, to nearly 50% using concentrated supernatant. This protocol will be useful for investigators with applications that require efficient, stable, high level transgene expression in primary FLS.
15609261 A comparison of the performance characteristics of classification criteria for the diagnos 2004 Dec OBJECTIVE: To compare the accuracy of published classification criteria for the diagnosis of psoriatic arthritis (PsA) and to see whether data-derived classification criteria would be more accurate. METHODS: Data were abstracted from case-note review and radiographic review of patients identified with PsA or rheumatoid arthritis (RA) from 2 clinical disease registers. Each patient was classified according to 7 criteria sets. The test performance characteristics were compared using conditional logistic regression analysis. In an attempt to overcome the problems of the diagnostic gold standard, latent class analysis also was used to calculate test-performance characteristics. Classification and regression-tree methodology was used to derive new criteria and to indicate the diagnostic importance of particular data items, especially rheumatoid factor (RF). RESULTS: Four hundred ninety-nine patients were identified with RA (n=156) or PsA (n=343). Excluding the criteria of Fournie, which could not be applied in 24% of subjects, 446 cases could be classified by all of the other 6 methods. The most sensitive criteria for the diagnosis of PsA were those of Vasey and Espinoza, McGonagle, and Gladman (99%), whereas the others were significantly less sensitive (between 56% and 94%). The specificity of the criteria was high and statistically similar (between 93% and 99%). The Fournie criteria were the most difficult to use, whereas the Vasey and Espinoza and Moll and Wright criteria were the easiest (98% of subjects were able to be classified). A 2-latent class model found very similar test-performance characteristics. Logistic regression and classification and regression-tree models suggested that negative RF was not necessary for diagnosis in the presence of other characteristic features of PsA. CONCLUSIONS: Apart from the Bennett and European Spondyloarthropathy Study Group criteria, which have inadequate sensitivity, the published classification criteria for PsA have similar test-performance characteristics. These data suggest that the criteria proposed by Vasey and Espinoza, Gladman, or McGonagle are the most accurate and feasible in distinguishing between PsA and RA. Relevance International agreement about classification criteria for PsA will assist the interpretation of clinical and epidemiologic research. However, further prospective studies on unselected patients with and without PsA, including controls with non-rheumatoid inflammatory arthritis, are required to confirm these findings.
12685870 Autoantibodies directed against ribosomal proteins in systemic lupus erythematosus and rhe 2002 Nov To assess the specificity of autoantibodies (aAbs) directed against the ribosomal P-proteins (RPPaAbs) in patients with systemic lupus erythematosus (SLE) and to investigate aAbs directed to other ribosomal proteins, 100 SLE, 100 rheumatoid arthritis (RA), 25 thyroiditis and 20 blood-donors were analyzed in a comparative study using an immunoblotting technique. Forty-eight percent of SLB sera contained aAbs directed against the ribosomal proteins of the 60 S subunit compared to 9% for RA, 5% for blood donors and 0% for thyroiditis. RPPaAbs were only found in SLE (25%) and aAbs directed to a 31 kDa and/or a 28 kDa protein of the 60 S subunit were found with a statistically higher frequency for SLE compared to RA (p < 0.0001). aAbs directed to proteins of the 40 S subunit were present in 63% of the SLE sera compared to 42% for RA, 4% for thyroiditis and 5% for blood donors. The number of positive sera was not statistically different between SLE and RA but a much more intense reactivity was observed for SLE sera. These data shows that the aAbs against the ribosomal proteins, especially the P-proteins along with the 28 and 31 kDa proteins of the 60 S subunit proteins, can be considered as useful biological markers for t he diagnosis of SLE inclinical practice.
12847895 [Dynamic changes in synovitis activity after intra-articular administration of xefocam in 2003 AIM: To assess efficacy of intraarticular administration of lornoxicam (xefocam) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Xefocam was injected into the knee joints of 58 patients with RA once a week for 3 weeks in a dose 8 mg. The treatment efficacy was evaluated by changes in the severity of arthralgias, pain in the joints at palpation, circumference of the knee joints at the level of the upper edge of the patella, ultrasound and thermography of the knee joints. RESULTS: Xefocam relieved arthralgia (in 44 patients at least by 30%), pain in the joints at palpation and joint circumference. Ultrasound investigation registered a significant thinning of the synovial membrane and amount of exudates. CONCLUSION: If local steroid therapy is not definitely indicated, intraarticular administration of xefocam can be effectively used for suppression of moderate inflammation in the joints in RA patients.
12649399 FcgammaRIIIA-158V and rheumatoid arthritis: a confirmation study. 2003 Apr OBJECTIVES: To develop a robust assay for genotyping the FcgammaRIIIA-158V/F polymorphism and to confirm the putative association between the FcgammaRIIIA-158V allele and rheumatoid arthritis (RA). METHODS: This allelic association study examined the FcgammaRIIIA-158V/F polymorphism for association with RA. A novel single-stranded conformational polymorphism assay was used to genotype 828 RA patients and 581 controls from the UK. RESULTS: The FcgammaRIIIA-158V allele was associated with both RA (P=0.02) and nodules (P=0.04). Individuals homozygous for this higher affinity allele had a significantly increased risk of RA (OR 1.53, 95% CI 1.08-2.18) and the development of nodules (OR 2.20, 95% CI 1.20-4.01). There was no evidence of an interaction with the shared epitope. CONCLUSIONS: We have developed a novel assay to genotype the FcgammaRIIIA-158F/V polymorphism and confirmed that homozygosity for the FcgammaRIIIA-158V allele is associated with UK Caucasian RA, particularly in those individuals with nodules, suggesting FcgammaRIIIA may play a role in determining disease severity or in the development of nodules per se.
12867582 Association study between corticotrophin-releasing hormone genomic region (8q13) and rheum 2003 Dec OBJECTIVE: To investigate whether the corticotrophin-releasing hormone (CRH) genomic region confers genetic susceptibility to rheumatoid arthritis (RA) in the Spanish population. METHODS: DNA was obtained from 121 simplex RA families and 101 healthy controls, all from Spanish origin. Two microsatellites, CRHRA1 and CRHRA2, located 25 and 20 kb downstream respectively from the CRH gene were examined using a new multiplex design. Linkage disequilibrium (LD) between the markers was assessed and association studies were carried out using the transmission disequilibrium test (TDT) implemented in TRANSMIT. RESULTS: Both markers are in Hardy-Weinberg equilibrium and there is significant LD between them in the Spanish population. Neither the polymorphic alleles of CRHRA1 and CRHRA2 markers nor their resulting haplotypes were significantly associated to RA. The associated haplotype in the UK population (CRHRA1*10; CRHRA2*14) was undertransmitted in RA patients (12 obs vs 17.43 exp), although the difference is not statistically significant (P > 0.05). CONCLUSIONS: This is the first follow-up study of the association between the CRH genomic region and RA and suggests that the CRH gene may not be involved in the pathogenesis of RA in the Spanish population. Further studies in other populations will help untangle the real contribution of this genomic region to the susceptibility to RA.
15151525 Leflunomide in active rheumatoid arthritis: a prospective study in daily practice. 2004 Jun AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.