Browse

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

ID PMID Title PublicationDate abstract
12579006 Spontaneous divergent elbow dislocation after Sauve-Kapandji procedure. 2003 Jan This is a report on an unusual complication of the Sauve-Kapandji procedure in patients with rheumatoid arthritis. Two women with rheumatoid arthritis who previously had an ipsilateral Sauve-Kapandji procedure experienced spontaneous transverse divergent elbow dislocations without evident trauma. Their radiographs showed medial dislocation of the proximal ulna, which was separated from the radial head. The radial head and distal end of the ulnar shaft showed remarkable instability by a pronation and supination motion without the radial and ulnar shafts being separated from each other. Stress radiographic examination showed significant loosening of all ligaments except the medial collateral ligament around the elbow and did not show disruption of the interosseous membrane. A unique chronic twist radioulnar dissociation which consists of gross instability of the radial head and the distal ulna without disruption of the interosseous membrane was considered to cause instability of the humeroulnar joint, which results in medial dislocation of the proximal ulna. This report suggests that there is a direct cause and effect relationship between the residual distal ulnar instability and the development of transverse divergent dislocation of the elbow in patients with rheumatoid arthritis after the Sauve-Kapandji procedure.
15053454 Is it possible to predict radiological damage in early rheumatoid arthritis (RA)? A report 2004 Mar Our aim was to assess the occurrence, progression, and prognostic features for radiological damage in early rheumatoid arthritis (RA). We recruited an inception cohort of patients from rheumatology departments in 9 hospitals beginning in 1986. Standard clinical and laboratory assessments and radiographs of hands and feet were made at baseline and yearly, and scored using Larsen's method. The study included 866 patients with radiographic scores at baseline and at 3 years, of whom 279 (32%) had erosive damage at baseline, and 609 (70%) by 3 years. Baseline and first-year values for Larsen erosion score, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), hemoglobin, nodules, swollen joint count, grip strength, duration of symptoms, and presence of RA-associated shared epitope were all risk factors for 3 year radiological outcome. In the non-erosive group at baseline (68%), high RF and ESR correctly predicted erosions or not by 3 years in 67%. Severity of erosions was correctly predicted by Larsen and swollen joint scores at baseline (82% correct), and Larsen score and ESR at one year (90% correct). In conclusion, most patients had evidence of radiological erosions by 3 years, despite early treatment with conventional drug therapy. Prognosis for radiological outcome was possible using routinely obtained clinical and laboratory measures. Ninety percent correct classification, even at one year, is likely to be useful to clinicians managing treatment options in early RA.
12102473 Combination therapy with cyclosporine and methotrexate in patients with early rheumatoid a 2002 May OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.
12114269 Relationships between glucocorticoids and gonadal steroids in rheumatoid arthritis. 2002 Jun Gender and sex hormones are strongly related to the incidence and progression of autoimmune rheumatic diseases. Although sex steroids have been shown to have direct effects on the immune system, their influence in vivo may be mediated via interactions with third party systems including the hypothalamic-pituitary-adrenal axis. Such interactions are well demonstrated in experimental animals. In humans, there is increasing, although indirect, evidence that these interactions also occur. Possible interactions at the cell and gene level, with mutual antagonism or synergy between cortico- and gonadal steroids, open new exciting hypotheses that await clarification.
12021147 Clinical association of autoimmune diseases with diabetes mellitus: analysis from southern 2002 Apr The adult form of polyglandular autoimmune syndrome (type 2) is associated with disorders of the thyroid, adrenal, and pancreas (type 1 diabetes mellitus). We profile the clinical association of autoimmune diseases among patients from our center in southern India: autoimmune diseases were diagnosed in 1.68% of persons with diabetes mellitus (147/15,523). Diabetes mellitus was diagnosed in 2.3% of persons with hypothyroidism (33/1435) and in 4.35% with thyrotoxicosis (15/345).
15547082 HLA-DMA*0103 and HLA-DMB*0104 alleles as novel prognostic factors in rheumatoid arthritis. 2004 Dec OBJECTIVE: To evaluate HLA-DM alleles as markers for disease severity in rheumatoid arthritis (RA). METHODS: Two distinct cohorts of patients with RA were oligotyped for HLA-DB1 and HLA-DM genes using PCR amplified genomic DNA with sequence specific oligonucleotide probes. Cohort 1 comprised 199 unselected patients with RA (mean (SD) age 45.5 (13.5) years; disease duration 11.9(8.8) years), whose disease severity was assessed using Larsen score on hand and foot radiographs. Cohort 2 comprised 95 patients with severe RA and 70 patients with benign RA according to the Larsen method. RESULTS: In cohort 1, after stratification according to DRB1 genotypes, patients positive for HLA-DMA*0103 and negative for HLA-DRB1*04 tended to have greater articular damage on hands and wrists (p = 0.07 by Mann-Whitney U test) and reached statistical significance for the Larsen score per year (p = 0.05). This association between HLA-DMA*0103 and articular damage was especially observed in patients with HLA-DRB1*01. Similarly, HLA-DMB*0104 positive patients had higher Larsen score on hands and wrists (p = 0.02). This association was even stronger in DRB1*04 positive patients (p = 0.005). In cohort 2, HLA-DMA*0103 was associated with severe RA in patients negative for HLA-DRB1*04 (OD = 5.4; p = 0.014). HLA-DMB*0104 allele frequency tended to be higher in patients with severe RA but without reaching significance. CONCLUSION: This is the first study evaluating the role of HLA-DM genes in the severity of RA. Our results suggest that HLA-DMA*0103 and HLA-DMB*0104 alleles may represent new genetic markers of RA severity. The HLA-DMA*0103 allele tends to be associated with patients with RA negative for DRB1*04 and could predict a more severe form of disease especially in HLA-DRB1*01 positive patients. The HLA-DMB*0104 allele could have an additive effect in HLA-DRB1*04 patients. Combined determination of HLA-DM and HLA-DRB1 alleles could facilitate identification of patients likely to have a poor disease course.
14523571 Prevalence of atopy in rheumatoid arthritis in Sivas, Turkey. A prospective clinical study 2004 Sep Assumed mutual antagonism of T-helper cell (Th)1 and Th2 diseases suggests that the prevalence of atopy should be decreased in rheumatoid arthritis (RA). We tried to determine that prevalence. Sixty-two patients with RA and 61 with osteoarthritis (control group) were included in the study. A questionnaire was used concerning mainly the symptoms of atopy. Skin prick tests, pulmonary function tests, chest X-rays, immunoglobulin E levels, and eosinophil counts were obtained. The prevalences of asthma, hay fever, and eczema in the RA group were 3.2%, 14.5%, and 1.6%, respectively. In the control group, they were 6.5%, 22%, and 6.5%, respectively. There was no significant difference between groups. There was also no significant difference between immunoglobulin E levels. Eosinophil counts were higher in the control group, however these values were within the normal range. Skin prick tests were obtained in seven RA patients, and eight controls revealed increased positivity. The prevalence of atopy in rheumatoid arthritis was not different from that in the general population. Our study results cannot support the concept of Th1/Th2 mutual antagonism.
12070047 Glycoprotein V: the predominant target antigen in gold-induced autoimmune thrombocytopenia 2002 Jul 1 Autoimmune thrombocytopenia is generally caused by autoantibodies against glycoprotein (GP) IIb-IIIa or GPIb-IX and occasionally against GPIa-IIa or GPV. By investigating 38 rheumatoid arthritis (RA) patients on gold therapy, 10 with profound thrombocytopenia and 28 nonthrombocytopenic controls, we showed that in all 10 patients with thrombocytopenia, the platelet autoantibodies preferentially targeted GPV but the presence of gold was not required for their reactivity. Elevated levels of platelet-associated IgG (PAIgG) were observed in 8 of the 10 patients in whom the tests were performed. In 5 patients with sufficient autologous platelets, the GPV specificity of PAIgG was confirmed. Tests with GPV transfectants revealed that the antibodies reacted with GPV independent of GPIb alpha, GPIb beta, or GPIX. Autoantibodies recognizing GPV were not seen in the 28 nonthrombocytopenic control RA patients. Thus, GPV seems to be targeted in gold-induced autoimmune thrombocytopenia.
15201939 [IL-1Ra: its role in rheumatoid arthritis]. 2004 Jan Interleukin-1 (IL-1) is one of the pivotal cytokines in initiating and driving the processes of rheumatoid arthritis (RA), and the body's natural response, IL-1 receptor antagonist (IL-1Ra), has been shown conclusively to block its effects. IL-1 mediate several clinical symptoms of the inflammatory reaction (i.e. fever, pain, sleep disturbances). IL-1 is considered a key mediator in RA joint damage because of its greater capacity (greater than TNF) of increasing matrix degradation by inducing the production of MMPs and PGE2 in synovial cells, as well by its role as mediator of bone and cartilage destruction. In addition, IL-1 decreases the repair process by suppressing matrix synthesis and shows a strong synergism with TNF in inducing many inflammatory genes at both local and systemic level. The induced endogenous production of IL-1Ra, in presence of the RA synovitis, is too low to contrast the high affinity of IL-1 for the cell receptors. Therefore, IL-1Ra presence should result in very effective prevention of IL-1 signal transduction particularly in the inflammatory site. In laboratory and animal studies inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. IL-1Ra is a member of the IL-1 superfamily. The effects of different DMARDs on IL-1Ra levels in RA patients support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease. However, since anti TNF-alpha therapy it is not effective in all RA patients, nor does it fully control the arthritic process in affected joints of good responders and complete TNF suppression should be avoided, the combined treatment with intermediate doses of TNF and IL-1 blockers, reaching synergistic suppression of arthritis, seems warranted in RA.
14658104 Cemented first-time revision using Charnley cups: clinical outcome after 7 to 15 years fol 2003 Dec Forty-six consecutive polyethylene cups used in cemented first-time revision of the acetabulum were evaluated at repeated occasions up to mean 10.7 years (range, 0.5-16.3 years). At the last follow-up, 3 cups had been revised (6.5%), 2 because of loosening and 1 because of fracture of the acetabulum. Furthermore, 4 were radiographically loose, corresponding to a radiographic loosening rate of 13% and a mechanical failure rate (revision or radiographic loosening) of 15.2%. Presence of rheumatoid arthritis was the only predictor of mechanical failure (relative risk [RR] = 7.7, 95% confidence limits, 1.7-36.2; P =.002). In patients without rheumtoid arthritis, there was only 1 (2.6%) revision and 3 of 39 cases (7.7%) with mechanical failure. Recementation of a Charnley cup in first-time revisions results in a low failure rate in an elderly, nonrheumatoid arthritis population with small or moderate bone deficiencies.
15225365 A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus a 2004 Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis (RA) by years. A nested case-control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of shared epitope (SE) genes, defined as HLA-DRB1*0404 or DRB1*0401, and of anti-CCP antibodies and RFs in individuals who subsequently developed RA. Patients with RA were identified from among blood donors whose samples had been collected years before the onset of symptoms. Controls matched for age, sex, and date of sampling were selected randomly from the same cohort. The SE genes were identified by polymerase chain reaction sequence-specific primers. Anti-CCP2 antibodies and RFs were determined using enzyme immunoassays. Fifty-nine individuals with RA were identified as blood donors, with a median antedating time of 2.0 years (interquartile range 0.9-3.9 years) before presenting with symptoms of RA. The sensitivity for SE as a diagnostic indicator for RA was 60% and the specificity was 64%. The corresponding figures for anti-CCP antibodies were 37% and 98%, and for RFs, 17-42% and 94%, respectively. In a logistic regression analysis, SE (odds ratio [OR] = 2.35), anti-CCP antibodies (OR = 15.9), and IgA-RF (OR = 6.8) significantly predicted RA. In a combination model analysis, anti-CCP antibodies combined with SE had the highest OR (66.8, 95% confidence interval 8.3-539.4) in predicting RA, compared with anti-CCP antibodies without SE (OR = 25.01, 95% confidence interval 2.8-222.2) or SE without anti-CCP antibodies (OR = 1.9, 95% confidence interval 0.9-4.2). This study showed that the presence of anti-CCP antibodies together with SE gene carriage is associated with a very high relative risk for future development of RA.
12527218 The role of innate cytokines in inflammatory response. 2003 Jan 22 Mediators produced by innate immune response cells such as macrophages can profoundly influence adaptive immunity. Recent studies have shown that IL-15 and IL-18 play an influential role in inflammatory response. Here I present recent data mainly from our own laboratories illustrating the importance of IL-15 and IL-18 in the induction and perpetuation of chronic inflammation during experimental and clinical rheumatoid synovitis. These findings suggest that antagonists to these cytokines may have a potential therapeutic role against organ-specific autoimmune diseases.
12932286 Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients 2003 We investigated whether plasma and synovial fluid (SF) samples from patients with rheumatoid arthritis (RA) contained extracellular mitochondrial DNA (mtDNA) or the oxidatively damaged DNA adduct 8-hydroxy-2'-deoxyguanosine (8-oxodG). Moreover, we correlated the laboratory findings of the patients with RA with their levels of mtDNA and 8-oxodG. SF and plasma samples from 54 patients with RA, SF from 30 non-arthritic control subjects, and plasma from 22 healthy volunteers were collected. The samples were subjected to polymerase chain reaction (PCR) using mitochondrial genomic primers, and the products were analyzed by SDS-polyacrylamide-gel electrophoresis. The intensities of the PCR-amplified bands were quantified and normalized to a reference sample. Furthermore, the SF samples were assayed by enzyme-linked immunosorbent assay for 8-oxodG. Extracellular PCR-amplifiable mtDNA was detected in the SF of 38 of 54 (70%) patients with RA, but not in any of the SF controls. PCR-amplifiable mtDNA was detected in the plasma of 30 of 54 (56%) of patients with RA and in 6 of 22 (27%) of the healthy volunteers. The levels of mtDNA in the plasma and SF samples of patients with RA were significantly higher (P < 0.0001) than in the respective control samples. The presence of both mtDNA and 8-oxodG in SF was significantly correlated with the presence of rheumatoid factor in the patients with RA. Extracellular mtDNA and oxidized DNA were detected in the SF of the great majority of patients with RA, but were absent or present at low levels in the control SF. These findings indicate that endogenous nucleic acid compounds might participate in joint inflammation by activating immune cells in the joints to produce proinflammatory cytokines.
15334429 Burden of caregiving: evidence of objective burden, subjective burden, and quality of life 2004 Aug 15 OBJECTIVE: To improve understanding of the nature and magnitude of the burden of informal care and also to indicate important areas for improving the current ways in which informal care is investigated. METHODS: Information on objective burden (such as care tasks performed and time investment), subjective burden (using the Caregiver Reaction Assessment instrument and a self-rated burden score), and quality of life (using the EuroQoL instrument) were collected in a postal questionnaire of 153 informal caregivers who provide care for rheumatoid arthritis (RA) patients. RESULTS: Caregivers had been caring for the RA patients on average for >11 years, reflecting the chronic nature of RA. They provide a substantial amount of care (27.4 hours per week) and are moderately strained (24.6 on the self-rated burden scale). Caregivers are relatively healthy on average but caregivers of more severe RA patients are relatively unhealthy, which may indicate health losses due to caregiving. CONCLUSION: Informal care can be burdensome in the context of RA. More information may help assist informal caregivers in caring for RA patients and help to avoid health problems and high subjective burden.
15188331 Unmet demands for health care among patients with rheumatoid arthritis: indications for un 2004 Jun 15 OBJECTIVE: To assess the prevalence of unmet health care demands among rheumatoid arthritis (RA) patients, and to determine if these unmet demands indicate underuse. METHODS: A total of 679 patients with RA participated in a questionnaire survey and clinical examination. Unmet health care demands and health care use were assessed for orthopedic care, allied health care, home care, and psychosocial care. Indications for underuse were determined by comparing health outcomes of patients with unmet health care demands and of health care users. RESULTS: Of the 679 patients, 28.7% had an unmet demand for 1 of the 4 services: 13.4% for allied health care, 9.7% for orthopedic care, 9.4% for home care, and 6.2% for psychosocial care. Underuse of allied health care, home care and psychosocial care was observed. CONCLUSION: Unmet demands for health care are frequent among RA patients. Most unmet demands indicate underuse. Health care professionals should therefore be more responsive to the demands of patients.
12060849 Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis patients. 2002 Jul The proteins of homeobox (HOX) genes are transcription regulators involved in cell type-specific differentiation and patterning of the body plan in vertebrates. Particularly, the HOXD family is involved in limb formation in mice and chicks. There is also some evidence that the HOXD9 gene, a member of the HOXD family, is involved in the pathology of rheumatoid arthritis (RA). The purpose of the present study was to determine if the HOXD9 protein was expressed in RA synovium and then to characterize the HOXD9-expressing cell. Western blotting and immunohistochemical analysis showed that the HOXD9 protein was expressed in the synovium from patients with RA, but not in those from patients with osteoarthritis or healthy individuals. The HOXD9-positive cells were localized in both the lining and sublining areas of the synovium. Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS). These findings not only indicate that the HOXD9 gene is exclusively expressed in the RA synovium but also suggest that the HOXD9 gene contributes to the pathology of rheumatoid arthritis through the FLS.
12707570 New role for an old friend: prednisone is a disease-modifying agent in early rheumatoid ar 2003 May There has been a renewed interest in the use of low doses of prednisone in the treatment of early rheumatoid arthritis. This is because it has been conclusively shown that low doses of prednisone retard bone damage, and physicians use prednisone because it helps control tender and swollen joints. Two studies appeared in 2002, one by van Everdingen et al. and one by Landewe et al. demonstrating the reduction of bone damage in early RA with the use of prednisone. Van Everdingen used 10 mg/day of prednisone and Landewe used an initial high dose of 60 mg/day of prednisone for a week, tapering off by 6 months. The bone sparing effect was still evident at 5 years. Low doses of prednisone are well tolerated, with documented side effects including weight gain, ecchymosis, and osteopenia.
12723729 Anakinra: the first interleukin-1 inhibitor in the treatment of rheumatoid arthritis. 2003 Apr Rheumatoid arthritis is an immunologically mediated inflammation of joints of unknown aetiology and often leads to disability. This inflammatory process may also involve extra-articular connective tissue. New therapeutic approaches have been made by inhibition of proinflammatory cytokines. Interleukin-1 (IL-1) is regarded as one of the most important mediators in the development of synovialitis. In this article, anakinra (Kineret), the first direct antagonist to IL-1, is discussed, in particular the efficacy and safety data from clinical trials. More than 10,000 patients have been treated with anakinra with significant improvement of inflammation and pain; the rate of radiologically visible progressive joint damage was significantly reduced. Among the adverse events, injection site reactions were most frequent, followed by a mild increase in infections. No activation of tuberculosis, as in tumour necrosis factor-alpha antagonist administration, has so far been reported.
11840436 COBRA combination therapy in patients with early rheumatoid arthritis: long-term structura 2002 Feb OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. METHODS: All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.
11817993 Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: 2002 OBJECTIVE: To compare disease-related medical care and productivity costs, and utilities, in 482 patients with rheumatoid arthritis randomised to receive leflunomide, methotrexate or placebo during a 12-month period. DESIGN AND SETTING: Prospective pharmacoeconomic analysis of a 1-year randomised double-blind trial set in North America. PERSPECTIVE: Societal and the Ontario Ministry of Health. METHODS: Information on healthcare resources, out-of-pocket expenses, loss of working time and time spent on chores, related to the disease or the medication, were collected at 4-week intervals and at study discontinuation. Rating scale and standard gamble (SG) utilities (0 = worse; 100 = best) were collected at baseline and at 6 and 12 months or study exit. Medical care costs in Canadian dollars (Can dollars) were calculated using Ontario reimbursement schedules. US patients' expenses were converted to Can dollars using 1995 purchasing power parity. Lost wages were calculated by age and gender according to 1995 Canadian wage data. All costs were adjusted to 1999 Can dollars and arithmetic mean costs were compared using the nonparametric bootstrap. Analysis of covariance was performed to compare utilities between groups. RESULTS: Mean (standard deviation) rating scale values and SG utilities, respectively, for leflunomide, methotrexate and placebo were 67.7 (18.0), 64.8 (18.1) and 57.5 (9.2), and 80.2 (22.1), 83.2 (18.0) and 77.0 (20.5). Both leflunomide and methotrexate had higher rating scale values (p < 0.05) compared with placebo; SG utilities were significantly different between methotrexate and placebo (p < 0.05). Annualised total rheumatoid arthritisb- or drug-related costs for leflunomide, methotrexate and placebo, respectively, were Can dollars 1761, Can dollars 1280 and Can dollars 1324, and medical care costs were Can dollars 753, Can dollars 620 and Can dollars 167 (all costs exclude drug acquisition and monitoring costs). Annual drug acquisition/ routine monitoring costs were estimated, respectively, at Can dollars 3853/Can dollars 483 for leflunomide and Can dollars 258/Can dollars 599 for methotrexate. Differences between overall costs (excluding drug acquisition and monitoring costs) and medical care costs were not statistically significant. The costs of treating patients with leflunomide were significantly higher than for methotrexate when drug acquisition and monitoring costs were included (p < 0.0001). CONCLUSIONS: No statistically significant differences in utilities could be found between leflunomide or methotrexate. When drug monitoring and acquisition costs are excluded, leflunomide has an otherwise similar economic profile compared with methotrexate, the current gold standard. The acquisition cost of leflunomide is a driving factor in increasing the costs of therapy. These higher costs need to be assessed relative to the therapeutic value of leflunomide.