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ID PMID Title PublicationDate abstract
14673971 Factors contributing to possession and use of walking aids among persons with rheumatoid a 2003 Dec 15 OBJECTIVE: To investigate the possession and use of walking aids among patients with rheumatoid arthritis (RA) or osteoarthritis (OA), and to identify factors contributing to possession and actual use of these aids. METHODS: A random sample of 640 patients with RA or OA was derived from a database of 6,500 registered patients. A total of 410 (64%) patients (223 RA, 187 OA) completed a questionnaire on possession and use of walking aids. Demographics, disease-related characteristics, and information about possession and use were assessed. Logistic regression analyses were used to determine which factors are associated with the possession and use of walking aids. RESULTS: Forty-nine percent of the RA patients and 44% of the OA patients owned a walking aid. Canes, forearm crutches, walkers, and orthopedic footwear were most frequently possessed. In the RA group, age, education, frequency of pain, and disability were associated with possessing a walking aid. In the OA group, age and disability were associated with possession. Approximately 30% of the owners did not use their walking aid. Factors associated with the actual use of an aid included higher age, a high intensity of pain, more disability, decrease in morning stiffness by the aid, and a positive evaluation of the aid. CONCLUSION: Almost half of patients with RA or OA possess a walking aid. Disability, pain, and age-related impairments seem to determine the need for a walking aid. Nonuse is associated with less need, negative outcome, and negative evaluation of the walking aid.
12579595 Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study. 2003 Feb 15 OBJECTIVE: To analyze the annual cost of rheumatoid arthritis (RA) and its predictive factors. METHODS: Data were obtained from a 12-month retrospective cohort of 201 RA patients, randomly selected from a rheumatology registry, through a structured interview and records of the Central Information System of the hospital. Results were divided into direct, indirect, and total costs in 2001 US dollars. A sensitivity analysis was performed. Multiple linear regression models for the different types of costs were carried out. RESULTS: The total cost was US dollars 2.2 million per year, with a cost attributable to RA of US dollars 2.07 million per year. The average cost per patient was US dollars 10419 per year (ranging from US dollars 7914 per patient per year in the best scenario to US dollars 12922 per patient per year in the worst case). Direct costs represent nearly 70% of total costs. We found an average increment in total costs of US dollars 11184 per year per unit of Health Assessment Questionnaire (HAQ) score (P < 0.0001) and an average annual increment of US dollars 621 per year of disease (P < 0.0001). After adjustment, the HAQ score, inability to perform housework tasks, and being permanently disabled for work were the only predictors of high costs. CONCLUSION: Our data show a remarkable economic impact of RA over society and link the costs of the disease to its consequences in terms of functional disability, work disability, and housework disability.
14667562 Smoking, gender and rheumatoid arthritis-epidemiological clues to etiology. Results from t 2003 Dec OBJECTIVES: This study was undertaken to confirm and extend our earlier observation that gender is a biological effect modifier of smoking-rheumatoid arthritis (RA) relationship in a diverse national survey sample in the United States. METHODS: Smoking history of 644 cases of RA and 1509 geographically matched general population controls were compared using weighted logistic regression. RESULTS: There were 644 respondents with RA (cases) and 1509 geographically matched controls. Cases were significantly younger, less educated, more likely to be single and female than controls. Among cases 57% were smokers while among controls 49% smoked. Among women, after adjusting for age, hysterectomy had an age adjusted odds ratio 1.45, (95% CI 0.99-2.10) and menopause an adjusted odds ratio 1.18 (95% CI 0.99-2.10) were associated with smoking. In univariable analysis ever-smoking was associated with increased risk of RA (odds ratio 1.34, 95% CI 1.0-1.81). Among the strata of smokers, there was an increasing gradient of risk with increasing exposure to smoking (P = 0.041). In separate multivariable models, smoking increased the risk in men (odds ratio 2.29, 95% CI 1.35-3.90) while in women the risk was not elevated (odds ratio 0.98, 95% CI 0.67-1.42). After adjusting for the statistically significant interaction both female gender (odds ratio 2.30, 95% CI 1.39-3.83) and having ever smoked (odds ratio 2.31, 95% CI 1.36-3.94) emerged as significant risk factors for RA. CONCLUSIONS: Gender interacts with smoking in by an unknown mechanism to lead to differential risk of RA.
12734884 Role of Fcgamma receptors IIA, IIIA, and IIIB in susceptibility to rheumatoid arthritis. 2003 May OBJECTIVE: To investigate the role of Fcg receptor (FcgR) genes in susceptibility to rheumatoid arthritis (RA) using family based studies, to examine possible interactions between FcgR genotypes and the shared epitope (SE), and to assess linkage disequilibrium between FcgR loci. METHODS: Association studies were performed in 95 Caucasian, single-case, nuclear Caucasian families with both parents alive using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) statistics. Three FcgR polymorphisms (FcgRIIA-131H/R, FcgRIIIA-158V/F, and FcgRIIIB-NA1/NA2) were genotyped using polymerase chain reaction methods. Linkage analysis was performed using 3 microsatellite markers (D1S498, D1S2844, D1S2762) flanking the FcgR region in an independent set of 90 Caucasian, multiple-case families. Potential effects of disease heterogeneity, including sex and the presence of rheumatoid factor, SE, and erosive or nodular disease, were taken into account in the analysis. Logistic regression analysis was performed to determine whether FcgR alleles are independent risk factors for the susceptibility to and/or severity of RA. Linkage disequilibrium was calculated using pairwise linkage disequilibrium statistics. RESULTS: HHRR and TDT analysis showed no evidence of preferential transmission of any FcgR alleles studied, and there were no important associations with any given disease phenotype. Moreover, neither linkage to microsatellite markers close to the FcgR genes on chromosome 1 nor linkage disequilibrium between FcgR loci was present in our population. The distribution of inherited genotypes provided evidence for an interaction between the SE and the FcgRIIIA-158V allele and between the SE and the FcgRIIIA-158V-FcgRIIA-131H 2-locus haplotype since the combined presence of these factors increased the susceptibility to RA (OR 4.13, 95% CI 1.6-10.62 and OR 2.83, 95% CI 1.25-6.38, respectively). However, regression analysis showed that neither the 158V allele nor the 158V-131H haplotype contributed as independent factors to susceptibility or severity of RA. CONCLUSION: Isolated FcgR genes do not play a major independent role in susceptibility to RA. To a limited extent, the presence of high-binding alleles at the FcgRIIIA locus or at the FcgRIIIA-FcgRIIA haplotype might predispose to RA in SE positive individuals.
14994390 Patient retention and hand-wrist radiograph progression of rheumatoid arthritis during a 3 2004 Mar OBJECTIVE: To quantitate patient retention and radiographic progression rates in serial hand/wrist radiographs of patients with rheumatoid arthritis (RA) who were not being treated with disease modifying antirheumatic drugs (DMARD). METHODS: A total of 1433 RA patients with 1-7 years' disease duration entered a 3-year prospective randomized double-blind clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (300 or 1000 mg daily) and ibuprofen (2400 mg daily). Standardized hand/wrist radiographs were obtained yearly and at dropout if > 6 months after entry. DMARD were not permitted. Joint erosion, joint space narrowing (JSN), and total scores of 3 readers were averaged. RESULTS: At entry, mean duration of RA was 3.5 years (range 1-7); ages were 21-78 years; patients were 71% female, 84% Caucasian, 67% rheumatoid factor (RF) positive; tender joint count was 29, swollen joint count 22, Westergren erythrocyte sedimentation rate (ESR) 49, and C-reactive protein (CRP) 2.44. There were 824 (57.5%) patients who completed >or= 6 months and had paired radiographs; 46% completed 48 weeks; 31%, 98 weeks; and 19%, 147 weeks. Months between paired radiographs (time in study) averaged 23.1 (range 6-36). Mean progression rates for total, erosion, and JSN scores (5.08, 2.53, and 2.54 units per year, respectively) were significantly associated with time in study, baseline RF, ESR, CRP, swollen joint count, presence of erosions at entry, and with 20% and 50% composite clinical responses. Painful joint count and RA duration were weakly associated only with progression of erosions. Progression rates were not associated with age, sex, corticosteroid use, or prior DMARD use. Patients who completed the 3-year trial had less severe disease activity and radiographic progression than those who dropped out. CONCLUSION: In this 3-year prospective double-blind clinical trial that prohibited DMARD, retention rates (57.5%, 46%, 31%, and 19% at 0.5, 1, 2, and 3 years) were similar to those in the non-DMARD-treated placebo groups of recent published studies. Radiographic progression rates are reported for 824 non-DMARD-treated patients during RA of 1-10 years' duration. This information may be useful as background information in the interpretation of longterm clinical trials that evaluate joint radiographic outcomes.
15823761 Anakinra: review of recombinant human interleukin-I receptor antagonist in the treatment o 2004 Dec BACKGROUND: Interleukin-1 (IL-1) plays an important role in the pathophysiology and progression of rheumatoid arthritis (RA) by contributing to destruction of cartilage, bone, and periarticular tissues. Inhibiting IL-1 synthesis or activity with the use of recombinant human IL-1 receptor antagonist (anakinra) may prove to be an effective approach to the treatment of RA. OBJECTIVE: The purpose of this article is to review the effects of anakinra in the treatment of RA. METHODS: A MEDLINE search from 1982 to 2003 was used to identify animal studies and randomized clinical trials of anakinra and other therapies that target IL-1. RESULTS: Clinical trials of anakinra have shown that it reduces the signs and symptoms of active disease and slows the rate of radiographic destruction in adults with RA. With anakinra 150 mg/d, 43% of patients achieved an American College of Rheumatology (ACR) 20% response, compared with 27% with placebo (P = 0.014). The ACR20 score indicates at least 20% improvement in the ACR composite score, which includes assessment of tender and swollen joint count, and other clinical end points such as pain and disability assessment. Patients treated with anakinra also experienced a 59% reduction in new bony erosion compared with controls (P < 0.001) and a 65% reduction in joint space narrowing as measured by the modified Sharp score (P = 0.020). Injection-site reactions were the most commonly reported adverse event, occurring in 50%, 73%, and 81% of patients receiving anakinra 30, 75, and 150 mg/d, respectively, compared with 25% of patients receiving placebo. Few serious adverse events were reported, and they typically occurred in patients receiving the highest daily dosage. CONCLUSIONS: IL-1 is an important cytokine in promoting the damage associated with RA. Anakinra is mildly to moderately effective and well tolerated in patients with active RA when used as monotherapy or in combination with methotrexate.
15207950 Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-con 2004 Jun 19 BACKGROUND: Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk. METHODS: 116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat. FINDINGS: At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo. INTERPRETATION: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.
11925904 [A multicenter cross-sectional study on the health related quality of life of patients wit 2002 Feb OBJECTIVE: To survey the actual conditions of medical care costs incurred by Japanese patients with rheumatoid arthritis, and to investigate impacts of health status, demographic and socioeconomic factors, clinical and laboratory measures, and medications on disease costs. METHODS: Self-reported health status questionnaires of the revised Japanese version of AIMS 2, and reports on out-of-pocket medical care costs were collected from 1471 patients with classical and definite rheumatoid arthritis recruited through the arthritis study group of Ministry of Public Health and Welfare consisting of eleven arthritis centers across the country during three months from September, 1994. Impacts of health status and other demographic and clinical factors on medical care costs were statistically analyzed by using chi-square tests for categorical variables and Spearman's rank correlation analysis for numerical variables. RESULTS: 1. Averaged out-of-pocket medical care costs for RA patients was estimated at yen 25,225 ($253.5) per person-month in 1994, in which direct medical care costs accounted for 53.9% and indirect medical care costs accounted for 46.1% of the total. Averaged substantial direct medical care costs including the costs covered by the public health insurance in addition to out-of-pocket costs was estimated at yen 512,000 ($5,140) per person-year based on the averaged 11.8% self-pay rate of the public health insurance in 1994. 2. The distribution curve of the total out-of-pocket medical care costs was highly skewed. Averaged total medical care costs in the 90th, 95th, and 100th percentiles were 4.5, 8.1, and 48 times as large as those in the median percentile, respectively. 3. Out-of-pocket direct medical care costs totaled in the top 1 and 5 percentiles reached 26.6%, and 57.6% of those in whole patients, respectively. 4. Variables most strongly related to the total out-of-pocket medical care costs were work disability in AIMS health status scales, followed by physical disability, rate of functional decline, pain, affect, daily dose of oral prednisolone, global assessment by physician, joint counts, blood levels of CRP, ESR, grip strength, blood concentrations of hemoglobin, age, Steinbrocker's class, sex, and medications, in this order. 5. There was a trend of increase in number of cases of male, middle aged, with lower levels of formal education and annual income, longer disease duration of 20 years or more, and single (male) or separated (female) in marital status, as the total out-of-pocket medical care costs increased. 6. The average rate of missed days due to illness to whole working days of RA patients was estimated at 21.9%. With increase in the rate of missed days, the annual income of RA patients decreased, indicating that the lower annual income of RA patents possibly resulted from their work disabilities. Based on the rate of missed days, the average earning loss due to the illness in RA patients was estimated approximately at yen 650,000 ($6,540) perperson-year, which was equivalent to 1.3 times the average direct medical care costs for RA per person-year. CONCLUSION: The costs of RA were strongly related to work disability and other health status as represented by AIMS-HRQOL scores. A small number of patents severely disabled shared a disproportionately large part of medical care costs. To reduce the costs, the measures to prevent the development of disability are most important.
12055773 Negative social perception of hypothetical workers with rheumatoid arthritis. 2002 Jun In the present study, 340 college subjects evaluated the job performance of hypothetical workers of varying health status, to test the hypothesis that workers with rheumatoid arthritis (RA) are more negatively perceived than other workers (paraplegic, healthy) despite equivalence in age, sex, education, job history, and time off from work for medical reasons. Results indicated that workers with RA are perceived as having significantly poorer interpersonal job skills and are deserving of significantly poorer scores for overall job performance, although no differences were obtained in the ratings of their job commitment or job expertise. The suggestion is made that an unfavorable social reaction to RA patients in the workplace is one factor that impairs the development of social support for these patients at work and contributes to their inflated disability rate.
12814018 [Diagnostic image (141) Nodules in a patient with rheumatoid arthritis. Multicentric retic 2003 May 31 A 59-year-old man presented with polyarthritis and noduli on fingers and buccal mucous membrane due to multicentric reticulohistiocytosis. This was a paraneoplastic manifestation of a renal cell carcinoma, and regression of noduli was seen after nephrectomy.
15469389 Molecular targets in immune-mediated diseases: focus on rheumatoid arthritis. 2004 Oct There are a large number of diseases involving inappropriate activation of the immune system. This review focuses on one such disease, rheumatoid arthritis (RA). Over recent years there has been a dramatic shift in the treatment of RA, in which biological agents, such as monoclonal antibodies and immuno-fusion proteins, have offered the potential to enhance or replace conventional immunosuppressive therapies. This review covers some of the novel biological molecules currently under investigation as potential therapeutic targets in RA. In addition, it covers the genomic and proteomic strategies being used to identify potential new molecular targets for future therapies. Selectively blocking the immune response, in a combination approach blocking not only inflammation but also the adaptive memory response and tissue destruction, holds great promise for the treatment of RA and many other immune-mediated diseases.
11877633 Coincidence of recurrent arthritis and Behçet's disease following anterior cruciate ligam 2002 Mar Chronic recurrent inflammation with joint effusion following anterior cruciate ligament (ACL) reconstruction is common. We report an unusual case of a patient also suffering from undiagnosed Behçet's disease. The patient had chronic recurrent joint effusions of the knee 7 years after traumatic rupture of the ACL and autologous tendon reconstruction using a hamstring tendon autograft. Arthroscopic treatment of the notch impingement and therapy of the accompanying rheumatic disease relieved the patient of his ailment. On the one hand, this case report shows the necessity of including chronic rheumatoid joint disease in the differential diagnosis of a persistent impairment of joint homeostasis following ACL reconstruction, and on the other hand it shows the coincidence of Behçet's disease and recurrent joint inflammation in a patient following ACL surgery.
12110154 How does infliximab work in rheumatoid arthritis? 2002 Since the initial characterization of tumor necrosis factor alpha (TNFalpha), it has become clear that TNFalpha has diverse biologic activity. The realization that TNFalpha plays a role in rheumatoid arthritis (RA) has led to the development of anti-TNF agents for the treatment of RA. Infliximab, a chimeric monoclonal antibody that specifically, and with high affinity, binds to TNFalpha and neutralizes the cytokine, is currently approved for the treatment of RA and Crohn's disease, another immune-inflammatory disorder. In addition to establishing the safety and efficacy of infliximab, clinical research has also provided insights into the complex cellular and cytokine-dependent pathways involved in the pathophysiology of RA, including evidence that supports TNFalpha involvement in cytokine regulation, cell recruitment, angiogenesis, and tissue destruction.
12080556 [Antigliadin antibodies in rheumatoid arthritis]. 2002 Feb We had study on the antibodies antigliadin type IgA in 40 patients having rheumatoid arthritis (33 Women and 7 men; middle age 51 years; rheumatoid factors was positive in 60%; the follow up of patient is 5.9 years). The technique applied is by ELISA. All the patients benefited of malabsorption biological test; of the immunoglobulins; and complex of histocompatibility (HLA); and gastrointestinal exploration composed of: fibroscopy duodno-jejunal with systematic biopsies. The search for this antibodies antigliadin (AAG) showed itself negative at all patients. Has histology, all these patients have a height villies normal. The abnormalities had been found in 37.5%, are minor partial intestinal villi, cellular infiltration of chorion and intraepithelial infiltration by lymphocytes more then 40%. By the way, we discuss the different mechanisms of these digestive involvment.
12931243 Hematopoietic stem cell transplantation for severe rheumatoid arthritis. 2003 Aug The substantial morbidity and mortality associated with rheumatoid arthritis (RA), while not widely appreciated, provide adequate justification for consideration of high-dose immunoablative therapy followed by hematopoietic stem cell transplantation. While some patients with RA follow a benign course, selected subsets of patients have been identified with 5-year survival rates of 40-70%. A number of factors that can be easily determined serve as useful prognostic indicators for poor outcome. These include the presence of many involved joints (total joint count), the degree of functional disability as measured by the health assessment questionnaire and the presence of rheumatoid factor. This article summarises the present status of hematopoietic stem cell transplantation for rheumatoid arthritis and proposes future directions for research.
12617039 [Pharmacological profile of anti-human TNF alpha monoclonal antibody, infliximab (Remicade 2003 Jan TNF alpha (tumor necrosis factor-alpha) plays an important role in the pathogenesis of inflammatory diseases including Crohn's disease and rheumatoid arthritis. Infliximab (Remicade) is a chimeric monoclonal antibody that recognizes human TNF alpha. Clinical trials trials have been persuasive that infliximab is effective in both Crohn's disease and rheumatoid arthritis. Infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying anti-rheumatic drugs, in terms of reducing symptoms and signs, inhibiting the progression of structural damage and improving physical function.
11950579 Use of the blood transfusion service in total knee replacement arthroplasty. The cost impl 2002 May In view of the rising costs of blood transfusion and reports of inappropriate transfusions an audit of the local practice was organised. The aim was to investigate whether blood transfusion in primary unilateral Total Knee replacement Arthroplasty (TKA) operations was being used inappropriately locally, the resultant cost implications and suggest ways of reducing these. A 1-year retrospective survey of blood transfusion practice was conducted for all consecutive elective, primary, unilateral TKA operations at a District-General Hospital. 169 operations were performed and 58 (34%) patients were transfused. A retrospective Haemoglobin concentration (Hb) analysis was performed for all the transfused patients to identify the number of transfusions that satisfied the suggested transfusion criteria of a threshold Hb of 8 g/dl and when indicated, a minimum transfusion of 2 units. Complete transfusion data was available on 49/58 (84%) patients transfused. When applying the above criteria to this sample, the potential annual saving for the department was estimated at approximately 8000 pounds Sterling; only 9 of these patients were deemed to be appropriately transfused.
15471892 Raised granzyme B levels are associated with erosions in patients with early rheumatoid fa 2005 May BACKGROUND: Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. OBJECTIVE: To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. METHODS: 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. RESULTS: Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients (mean (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p<0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis (odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p<0.05). CONCLUSIONS: Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease.
14508644 [NeuFlex Silastic implant in metacarpophalangeal joint arthroplasty]. 2003 Sep The NeuFlex joint implant is, like the Swanson prosthesis, a silicone-spacer-implant for metacarpophalangeal arthroplasty in rheumatoid arthritis or osteoarthritis. The implant design differs essentially through a preformed, 30 degrees anatomically neutral angle and palmar lying movement center, which reduces strain across the hinge by 35%. The Swanson prosthesis is straight with a dorsal lying movement center. The advantage of this new design is an improved overall function arc and range of movement in the MCP-joint with a better grip-function. Results of simulator and laboratory tests are presented and interpreted. In 50 patients (168 MCP-joints), early results show an average functional arc of movement of 61 degrees and an average extensor lag of 12 degrees. The 30 degrees pre-bend angle, corresponding to the normal resting angle of the hand, and the improved flexor tendon excursion and moment arm appear to be the main reasons for the substantially improved flexion following use of the NeuFlex device.
12465144 Autoantibodies in early seropositive rheumatoid arthritis, before and during disease modif 2002 Dec OBJECTIVE: Autoantibodies observed in patients with rheumatoid arthritis (RA) during clinical trials of immunomodulating agents may cause concern about possible induction of autoimmunity by the therapeutic intervention. We determined the frequency and variability of selected autoantibodies in patients with early rheumatoid factor (RF) positive RA during a prospective observational study. METHOD: The study cohort consisted of 276 patients with active RA and with RF > or = 40 IU, who were enrolled between January 1, 1993, and April 1, 2000, before starting disease modifying antirheumatic drug (DMARD) therapy (average duration of symptoms, 7 mo). During an average of 3.5 years followup, a panel of autoantibodies was determined at entry, 6 months, 12 months, and yearly thereafter, in addition to routine clinical, radiographic, and laboratory assessments. After enrollment, patients were treated with DMARD at the discretion of their rheumatologists. RESULTS: At entry before any DMARD therapy, antinuclear antibody (ANA; by HEp-2) values were negative in 31%, borderline (8 IU/ml) in 26%, and > 8 (mean 65.5 IU/ml) in 41%. Tender and swollen joint counts, Disease Activity Score, and RF values were significantly higher in those with ANA > 8. During followup 726 paired serial specimens were available; 12.5% changed from negative to positive ANA and 12.3% from positive to negative. Additional autoantibodies were present in specimens of 20% of the subjects; 8% had 2 and 1.4% had 3 other autoantibodies. Anti-dsDNA was detected in 13 (5.5%) patients; 4 changed from negative to positive and one from positive to negative. SSA IgG and SSB IgG autoantibodies were both present in one of these patients. Ribosomal P protein autoantibodies were noted in 2 other patients, but Sm (Smith) and uRNP/snRNP IgG autoantibodies were not present in any patient. No patient had a diagnosis of systemic lupus erythematosus. Antithyroid peroxidase (20 patients), parietal cell (15), smooth muscle (14), reticulin (9), mitochondrial (5), striational (2), SSB (2) and SCL-70 (1) autoantibodies were detected in some specimens. Seven patients were diagnosed with hypothyroidism, one with chronic thyroiditis, one with hepatitis C, and 9 with malignancies. CONCLUSION: In patients with early RF positive RA the frequent occurrence of autoantibodies before and during treatment with standard DMARD may make it difficult to attribute their presence to new therapies.