Browse

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

ID PMID Title PublicationDate abstract
20972600 Comparison of composite disease activity indices for rheumatoid arthritis. 2011 Apr To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.
20066425 Lag time between onset of symptoms and diagnosis in Venezuelan patients with rheumatoid ar 2011 May A retrospective study in a hospital-based sample of Venezuelan patients with rheumatoid arthritis was made to estimate the lag time between onset of symptoms, diagnosis, and initiation of DMARD treatment. Medical records and in-person interview of patients to fill in a questionnaire collecting information on demographics and initiation of symptoms, first consultation with any physician, time of diagnosis, and initiation of first disease-modifying anti-rheumatic drug were reviewed. We performed descriptive statistics and multivariable linear regression analysis. Mean lag time between symptom onset and diagnosis of rheumatoid arthritis was 40.5 months (range 1-424). Mean lag time between onset of symptoms and first consultation with a physician and between first consultation and diagnosis was 16.3 and 23.9 months, respectively. Mean lag time between onset of symptoms and initiation of DMARD treatment was 56.9 months. A definitive diagnosis of rheumatoid arthritis was done by a rheumatologist in 251 patients (92.3%). First consultation with an orthopedist or a primary care physician, first consultation in a public versus a private health center, and diagnosis before 2000 were associated with longer lag time between onset of symptoms and diagnosis. Venezuelan patients with rheumatoid arthritis had a marked delay from disease onset to diagnosis and initiation of first DMARD. First consultation with an orthopedist and consultation in a public versus a private health center were the variables with the strongest effect on lag time to diagnosis and to initiation of first DMARD.
22984270 Comparison of the 2010 American College of Rheumatology/European League Against Rheumatism 2012 Nov OBJECTIVE: To compare the performance of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria with the 1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis (RA) in an early arthritis cohort. METHODS: The study included 79 patients with early arthritis (symptoms < 12 months) and a minimum of 1 year of followup between January 2004 and August 2010. Case notes were reviewed to determine which criteria were fulfilled at initial, 3-month, 1-year, and 2-year visits. Requirements for disease-modifying antirheumatic drug (DMARD) therapy and presence of joint erosions were compared at 2 years. RESULTS: At the initial visit, twice as many patients fulfilled the 2010 criteria (67%) compared with the 1987 criteria (34%; p < 0.001). Forty-four percent of patients who fulfilled only the 2010 criteria at the initial visit went on to fulfill both 1987 and 2010 criteria at 3 months (p < 0.001). Eight patients did not meet the 1987 RA criteria solely because of short symptom duration. All 17/79 patients who developed joint erosions went on to eventually fulfill both criteria. Of those patients who fulfilled only the 2010 criteria at baseline, 25/27 (93%) ultimately received DMARD therapy compared with 24/26 (92%) of those fulfilling both 1987 and 2010 criteria. CONCLUSION: The 2010 ACR/EULAR RA criteria allowed earlier RA classification compared to the 1987 ARA criteria, although both criteria were equivalent in predicting joint erosions and subsequent need for DMARD (Australian New Zealand Clinical Trials Registry ANZCTR 12608000292370).
23013853 Great artists with rheumatoid arthritis: what did their disease and coping teach? Part I. 2012 Oct The famous artists Pierre-Auguste Renoir (1841-1919) and Alexej von Jawlensky (1864-1941) had rheumatoid arthritis (RA). Both represent an outstanding example of successful coping with RA in former times when treatment was very limited, and these individuals took advantage of creative disease management. The most popular French impressionist painter Renoir used his creativity to develop his own exercises and assistive equipments for painting despite his disability. Thus, Renoir exemplifies an artistic life altered by RA over more than 25 years that he dedicated entirely to his art and the depiction of beauty and happiness testified by his own words: "The pain passes, but the beauty remains." Jawlensky, a Russian from origin, was one of the most important expressionist painter active in Germany and the first painter in the 20th century who created extensive series of paintings especially of human faces. From Jawlensky, we learned that his rapidly progressing, late-onset RA induced depression, disability, financial pressure, and social retreat. But the resulting artistic sublimation contributed to the change in his paintings, which we owe the more than 1000 series of the very unique, small-format "Meditations."For those interested in art, new insight will be opened into the life and work of the artists and increase the appreciation for their contribution to modern art.
22836366 Neurological improvement and prognosis after occipito-thoracic fusion in patients with mut 2012 Dec INTRODUCTION: Mutilating-type rheumatoid arthritis, the most aggressive type of rheumatoid arthritis, is frequently associated with destructive cervical involvement, both at the high-cervical and subaxial levels, causing significant neurological deficit, and their natural course of the disease and the survival are discouraging. For such cases, we have been actively performing occipito-thoracic fusion since 1991. Although medical treatment for rheumatoid patients has represented a marked improvement, it could not treat all of these patients because of several reasons. Therefore, it is still important to evaluate the past treatment results. METHODS: We investigated the neurological improvement and prognosis in 51 mutilating-type rheumatoid arthritis patients who underwent occipito-thoracic fusion between 1991 and 2010. The neurological status was evaluated using modified Ranawat classification; class IIIB was subdivided into IIIBa (able to sit upright) and IIIBb (bedridden). RESULTS: The preoperative neurologic status was IIIBa in 19 patients and IIIBb in 17 patients. 15 of the 19 patients with class IIIBa improved to being able to walk (79 %), whereas only 3 of the 17 patients with class IIIBb improved to being able to walk (18 %) after surgery. Of the 51 patients, 28 died during follow-up; the mean age at death was 67.2 years. The postoperative 5- and 10-year survival rates were 60.3 and 26.4 %, respectively. CONCLUSION: The neurological improvement and prognosis after surgery was poorer in class IIIBb patients than in the other patient groups. Occipito-thoracic fusion can improve the neurological symptoms and prognosis. However, early surgical intervention is recommended, before a patient becomes bedridden (class IIIBb).
23239035 MicroRNA-155 as a therapeutic target for inflammatory diseases. 2013 Mar MicroRNAs are short non-coding molecules expressed in different tissues and regulate the transcription of different genes. They are highly specific in their action. Upregulation or downregulation of specific microRNAs has been observed during different diseases like cancers, embryogenesis, organogenesis, apoptosis and arthritis. They are also known to be involved in autoimmune diseases. MicroRNAs are also found to be stable and easy to validate. Differential expression of microRNA-155 has been studied by different groups in inflammatory diseases including arthritis along with other miRNAs. This suggests that it can be used as a potential biomarker or therapeutic in the autoimmune diseases, especially rheumatoid arthritis. Experimental studies are needed to explore their role as biomarker or therapeutic.
21914218 Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rhe 2011 INTRODUCTION: Binding immunoglobulin protein (BiP) has previously shown powerful anti-inflammatory properties in the collagen-induced arthritis (CIA) model, where a single dose of BiP has proved to be both a long-term prophylactic and therapeutic. In both CIA and human in vitro studies, BiP induced regulatory T cells. The present investigation looked at the anti-inflammatory effect of BiP on inflamed human synovial tissue transplanted into severe combined immunodeficient mice (SCID), a chimaeric in vivo model previously used to test the efficacy of biologic therapies. METHODS: Rheumatoid arthritis synovial membrane (RASM) was engrafted into SCID mice. Following successful engraftment, mice were intravenously injected with BiP or human serum albumin in the presence or absence of anti-IL-10 mAb. Twelve days later the grafts were removed for analysis and human cytokines in the sera were quantified by ELISA. The extent of residual inflammatory cellular infiltrate in the synovial explants was determined by weight of the explants. RESULTS: The RASM transplants from mice treated with BiP showed visual reduction in cellular infiltrate and downregulation of all quantifiable features of inflammation as assessed by the Koizumi or Rooney histological criteria. Also downregulated were HLA-DR, CD86, IL-6 and TNFα expression as assessed by immunohistology. ELISA detected significantly less human IL-6 circulating in the BiP-treated mouse serum. After removal of transplanted tissue 12 days post administration of BiP, the RASM explants from the BiP-treated SCID mice weighed significantly less, indicating a suppression of tissue inflammation. Mice given concomitant neutralising anti-IL-10 antibody and BiP showed no such suppression. CONCLUSIONS: BiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10.
22009608 Pathogenetic, clinical and pharmaco-economic assessment in rheumatoid arthritis (RA). 2011 Oct Rheumatoid arthritis (RA) has become one of the most studied autoimmune chronic inflammatory diseases (ACIDs), either from the pathogenetic or from the therapeutic point of view. It is recognized that synovial fibroblasts, TH1 and TH17 cells likely play along with the B cells the most relevant role. The disease has a polygenic background that characterizes the seropositive and the seronegative subsets. Over the years, we realized that no more than 15-20% of long-standing RA (LSRA) treated with conventional drugs can reach full remission, whereas the most recent data in early RA (ERA) have demonstrated that 40-60% can be put into clinical and biological remission. This of course is of crucial importance to avoid any progression of the structural damage that leads to functional disability. If we consider that a disability index score (Health Assessment Questionnaire 0-3) of a severe arthritis can cost up to 21,000 EUs, while a mild disease will cost not more than 5,500 EUs per year, it appears very clear that a low disease activity (LDA) or a remission state (Rem) should be the aim in each single patient, in order to keep the workability and maintain the productivity. This is and should be the major aim in each RA patient.
21325757 Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive 2011 OBJECTIVE: Body fat is an important source of hormones and cytokines (adipokines) that not only regulate the energy balance, but also regulate the inflammatory and immune responses. This study investigated the association of clinical conditions with serum levels of adipokines in patients with rheumatoid arthritis. METHODS: Serum levels of resistin, leptin, and adiponectin were measured by enzyme-linked immunosorbent assay in 141 patients (110 women) who fulfilled the 1987 revised criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis and in 146 normal controls (124 women). Then the correlations between adipokine levels and clinical parameters were evaluated. RESULTS: The serum resistin level did not differ between the patients and controls. However, serum leptin levels were significantly higher in male and female rheumatoid arthritis patients than in the corresponding controls, while the serum adiponectin level was significantly higher in female patients than in female controls. Multivariate analysis revealed that predictors of an elevated resistin level were female sex and C-reactive protein (CRP), while the leptin level was related to the body mass index and CRP. Predictors of an elevated adiponectin level were the use of prednisolone and CRP, however, CRP was negatively associated with adiponectin in patients with rheumatoid arthritis. CONCLUSION: The serum levels of resistin and leptin were positively associated with CRP level in patients with rheumatoid arthritis, suggesting that these adipokines may act as pro-inflammatory cytokines in this disease. The serum adiponectin level was elevated in the patients, however, it was negatively associated with CRP level. In addition, the serum levels of resistin, leptin, and adiponectin were also associated with female sex, BMI and the use of prednisolone, respectively.
22810704 Discrepancies between patients and physicians in their perceptions of rheumatoid arthritis 2012 Sep OBJECTIVE: Patients and physicians often differ in their perceptions of rheumatoid arthritis (RA) disease activity, as quantified by the patient's global assessment (PGA) and by the evaluator's global assessment (EGA). The purpose of this study was to explore the extent and reasons for this discordance. METHODS: We identified variance components for the PGA and EGA in RA patients who were starting therapy with methotrexate in an academic outpatient setting. We analyzed predictors of the observed discrepancy in these measures (calculated as the PGA minus the EGA) and in their changes (calculated as the PGA(change) minus the EGA(change) ). RESULTS: We identified 646 RA patients, and among them, 77.4% of the variability in the PGA and 66.7% of the variability in the EGA were explainable. The main determinants for the PGA were pain (75.6%), function (1.3%, by Health Assessment Questionnaire), and number of swollen joints (0.5%); those for the EGA were the number of swollen joints (60.9%), pain (4.5%), function (0.6%), C-reactive protein (0.4%), and the number of tender joints (0.3%). Increased pain led to a discrepancy toward worse patient perception, while increased numbers of swollen joints led to a discrepancy toward worse evaluator perception, both explaining 65% of the discordance between the PGA and the EGA. Likewise, changes in pain scores and numbers of swollen joints proved to be the main determinants for discrepant perceptions of changes in RA disease activity, explaining 34.6% and 12.5% of the discordance, respectively. CONCLUSION: The most significant determinants for the cross-sectional and longitudinal discrepancy between the PGA and the EGA are pain and joint swelling, respectively. Understanding the reasons for a discordant view of disease activity will help to facilitate the sharing of decision-making in the management of RA.
21115252 Herbal medicinal products target defined biochemical and molecular mediators of inflammato 2011 Jan 1 Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by synovial inflammation, damage to cartilage and bone, and deformities of the joints. Several drugs possessing anti-inflammatory and immunomodulatory properties are being used in the conventional (allopathic) system of medicine to treat RA. However, the long-term use of these drugs is associated with harmful side effects. Therefore, newer drugs with low or no toxicity for the treatment of RA are actively being sought. Interestingly, several herbs demonstrate anti-inflammatory and anti-arthritic activity. In this review, we describe the role of the major biochemical and molecular mediators in the pathogenesis of RA, and highlight the sites of action of herbal medicinal products that have anti-arthritic activity. With the rapidly increasing use of CAM products by patients with RA and other inflammation-related disorders, our review presents timely information validating the scientific rationale for the use of natural therapeutic products.
22509979 B-cell activating factor levels in rheumatoid arthritis patients in response to treatment 2012 Jul The B-cell-activating factor (BAFF), a member of the tumor necrosis factor (TNF) family, has recently attracted attention as a potent cytokine, involved in B-cell stimulation and survival of autoimmune cells. Despite its significance in the pathogenesis of autoimmune diseases, data is limited and inconclusive regarding its expression in different stages of rheumatoid arthritis (RA). The aim of this study was to assess BAFF in biologic-naïve RA patients with early versus established disease and monitor its levels in response to anti-TNF treatment in seronegative- and seropositive patients. Based on our results, B-cell-activating factor (BAFF) did not appear to be overexpressed or differentially expressed early (≤2 years duration) in comparison to established rheumatoid arthritis (RA). Moreover, tumor necrosis factor (TNF) blockade did not appear to affect BAFF levels in either seropositive or seronegative RA patients, despite the association of anti-TNF treatment with the development of autoantibodies and the known anti-apoptotic effects of BAFF. As expected, BAFF became induced after B-cell depletion. Investigation of the effect of different biologics on the expression of BAFF and other cytokines will help elucidate the interconnecting immune pathways involved in the initiation and perpetuation of the inflammatory process.
21794766 [Contribution of nurse-led clinics in the management of the patient with rheumatoid arthri 2011 Mar The goal of a nurse-led clinic in the management of rheumatoid arthritis patients is to promote patient independence. Patient education and empowerment are efficacious tools for achieving this. The main nursing care roles are vigilance of physical symptoms, drug toxicity and co-morbidities; management of physical and psychological symptoms; to provide continuity of care. There is evidence supporting the effectiveness of nurse-led clinics and the economic benefits related to it.
22775405 What constitutes uncertainty in systemic lupus erythematosus and rheumatoid arthritis? 2013 Patient uncertainty is associated with conditions with no known cause or cure, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and despite its potential role in chronic illness management, it is still a poorly understood concept. This study constitutes an in-depth investigation of patient uncertainty in SLE and RA. We conducted (i) structured interviews with a sample of rheumatology health care professionals (HCPs) (n = 8) and (ii) in-depth, semi-structured interviews with a sample of SLE (n = 17) and RA (n = 15) patients. Interviews were audio-taped, transcribed verbatim and analysed thematically using detailed line-by-line coding. Patient uncertainty was conceptualised in a framework of five domains: symptoms and prognosis, medical management, self-management, impact and social functioning. Even though these five domains were present in both the SLE and RA data, there were some differences at the sub-domain level. Several sources of uncertainty were put forward by the HCPs and subsequently confirmed in the patient interviews including the illness trajectory, age, gender and timing. Patients reported uncertainty relative to various aspects of their illness, its management and impact. Finally, HCPs discussed the behavioural and psychosocial impact of uncertainty, which further suggests its important role in patient management.
21327425 Extraarticular manifestations in Turkish patients with rheumatoid arthritis: impact of EAM 2012 Jun The aim of our study was to investigate extraarticular manifestations (EAMs) in Turkish patients with rheumatoid arthritis (RA) and also assess the impact of EAMs on various health-related quality of life (HRQoL) domains, including physical, social, emotional, mental functioning, and bodily pain. A total of 150 patients were included in the study. EAMs were identified clinically. Pulmonary involvement was confirmed by using pulmonary function tests (PFT) and high-resolution computed tomography (HRCT), atlantoaxial subluxation by cervical spine X-rays. Peripheral neuropathy, rheumatoid nodules, and Sicca symptoms were picked up on clinical examination. Peripheral neuropathy was also confirmed by electroneurophysiologic studies. Patients were evaluated by Rheumatoid Arthritis Quality of Life (RAQoL), and Short form-36 (SF36). The quadrivariate Disease Activity Score- 28 (DAS28) was used for measuring disease activity. Functional status was evaluated by using the Stanford Health Assessment Questionnaire (HAQ). The severity of pain was documented by using 10-cm Visual Analog Scale-Pain (VAS-pain). EAMs were observed in 50 patients (33.3%). These were pulmonary involvement (28.7%), rheumatoid nodules (14.7%), Sicca Syndrome (8%), peripheral neuropathy (2.7%), and atlantoaxial subluxation (0.7%), respectively. It was not recorded any statistically significant difference in HAQ, DAS28, VAS-pain, and RAQoL scores between the patient groups with and without EAMs. Patients with EAMs scored significantly lower in physical functioning, role-physical, and role-emotional subgroups of SF36 (P < 0.01). Presence of EAMs is not directly associated with disease activity and functional status, but influences negatively HRQoL including physical and emotional functioning.
20842405 Incidence of falls and fear of falling in Japanese patients with rheumatoid arthritis. 2011 Feb The objective of this study is to determine the incidence of falls and fear of falling by gender and age in Japanese patients with rheumatoid arthritis (RA). Among the Japanese patients who participated in a single-institute-based prospective observational cohort study of patients with RA, namely the Institute of Rheumatology Rheumatoid Arthritis, 765 men (median age 63 years) and 4,231 women (median age 60 years) with RA responded to questions related to falls. Eight percent of men and 11% of women reported one or more falls during the previous 6 months. At least one fall and multiple falls were significantly more frequent in men (p < 0.05) and in women (p < 0.001) with RA over age 65 and age 75 years, respectively, although there was no significant linear increase in risk with age. Sixteen percent of men and 22% of women reported fear of falling. More men over age 65 tended to report fear of falling than those under age 65 (p < 0.001), although the incidence of women with fear of falling increased with advancing age. Japanese patients with RA over age 65 and age 75 appeared to have a high risk of at least one fall and multiple falls, respectively.
22006430 Exploring occupational disruption among women after onset of rheumatoid arthritis. 2012 Feb OBJECTIVE: To portray experiences of women engaging in everyday tasks, activities, and occupations, from symptom onset to 12 months after diagnosis with rheumatoid arthritis (RA), and to explore the meanings attributed to their activities and occupations. METHODS: A secondary analysis of qualitative data, guided by phenomenography, explored the stories of 37 women with early RA. The original study used in-depth interviews to explore the help-seeking process from first symptom to diagnosis, and results indicated unexplored impacts on activity, stimulating the present analysis. Transcripts were read and coded by 3 investigators and then debated by the full team with this new research objective in mind. Descriptive categories were formed through a systematic, iterative approach with a focus on how early RA impacted daily routines and participation in occupation. RESULTS: Participants recounted a range of experiences characterized by changes in the way they engaged in occupations as a result of RA symptoms. Four interrelated categories were identified: uncertainties associated with good days, bad days, and worse days; experiencing activity disruption; doing things differently, which was perceived both positively and negatively; and changing views of self, as participants developed identities as individuals living with RA. CONCLUSION: Daily activities and occupational identity can be profoundly impacted in the first 12 months after diagnosis with RA, resulting in significant life changes. Health professionals are encouraged to identify disrupted activities, facilitate participation in valued occupations, and create environments that enable patients to explore changes in identity to prevent negative life consequences.
22890965 Users' experience of physical activity monitoring technology in rheumatoid arthritis. 2013 Jun OBJECTIVES: The aim of the present study was to qualitatively explore users' experiences of home monitoring of health with specific regard to physical activity monitors. METHODS: Fourteen participants were randomly selected from a larger sample of individuals with rheumatoid arthritis (RA) who had taken part in a physical activity monitoring study and had worn two physical activity monitors for seven days in their homes. These individuals were assigned to one of two focus groups. Each focus group lasted for between 40 minutes and an hour and was audio-recorded. A semi-structured questioning route was used, followed by subsequent theoretical thematic analysis. RESULTS: No statistically significant differences were noted in the demographic factors between those who took part in the focus groups and the entire RA sample. Three distinct themes were identified: i) Experiences of having health monitored in the home, which was found to be largely positive; ii) Experiences of use of specific technology to monitor physical activity, which was generally reported as unobtrusive and not to impact significantly negatively on their daily life; iii) Perceptions and experiences of physical activity and exercise, which monitoring was reported to facilitate focusing on physical activity choices. CONCLUSIONS: These focus groups were the first to highlight the perceptions held by individuals with RA regarding home monitoring and, in particular, physical activity monitoring. This has implications for those planning interventions for this group which involve home monitoring. Interesting findings were also highlighted regarding the perceptions and understanding of physical activity and exercise among people with RA.
21595176 [The meaning of biologic therapy in the treatment of rheumatoid arthritis with the focus o 2011 Apr Aims of management of rheumatoid arthritis (RA) patients are not only a delay in progression of the disease and improvement of motor function, but also inhibition of progress of joint damage and achievement of remission. Early RA diagnosis is important, allowing introduction of active therapy as early as possible. Immediate treatment with disease modifying anti-rheumatic drugs (DMARDs) is necessary. In case DMARDs fail to evoke an adequate therapeutic response, introduction of biological drugs should be considered. Failure to achieve remission in case of many patients treated with classic DMARDs was a stimulus for intensive research on new drugs. Introduction of tumour necrosis factor alpha (TNF-alpha) inhibitors to therapy of RA 15 years ago caused a significant progress in management of the disease. Five TNF-alpha inhibitors are currently authorised (Infliximab, Etanercept, Adalimumab, Certolizumab and Golimumab) for RA treatment. Numerous clinical trials and observational programs proved higher efficacy of a combination therapy consisting of MTX and a TNF-alpha inhibitor in terms of RA remission. That applies mainly to patients burdened with risk factors of fast progression of the disease.
22966891 Association of DHODH haplotype variants and response to leflunomide treatment in rheumatoi 2012 Sep AIM: Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has potentially serious side effects, targeting only those most likely to benefit would address a clinical need. We aimed to determine whether variations in the gene encoding DHODH, the molecular target of leflunomide, might include biomarkers that could be used to rationalize provision of this drug. MATERIALS & METHODS: We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with rheumatoid arthritis treated with leflunomide. Clinical response was determined by assessing the change in 28 joint disease activity score over the first 3 months of treatment. RESULTS & CONCLUSION: Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). This suggests that a functional variant in strong linkage disequilibrium with this haplotype may predispose to reduced leflunomide efficacy.