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

ID PMID Title PublicationDate abstract
10895379 Prediction of 20-year outcome at onset of seropositive rheumatoid arthritis. 2000 May OBJECTIVE: With the advent of new and expensive antirheumatic treatments with potentially serious side effects, it would be essential to identify as early as possible those rheumatoid arthritis (RA) patients who have a poor prognosis. Here study was made of the prognostic value of different markers recorded at the onset of RA. METHODS: At the 20-year follow-up of our prospective study, 66 patients had rheumatoid factor-positive (RF+) RA. At commencement of follow-up (disease duration < 6 months), the prognostic value of 19 demographic, laboratory, clinical and radiographic variables was tested to explain the 20-year Larsen score for peripheral joints and the Health Assessment Questionnaire (HAQ) index using Somers'd for asymmetrical associations. RESULTS: An association was observed between onset blood platelets (0.17), serum IgG (0.18), the onset Larsen score (0.33) and the 20-year Larsen score. Old age (0.30), serum orosomucoid (0.17), the function score (0.28), morning stiffness (0.28), and grip strength (0.24) were associated with the 20-year HAQ. CONCLUSION: The correlation between the investigated entry variables and end-point outcome was poor. In our discussion we conclude that the most important prognostic factor in RF + RA is the treatment.
9827131 [Identification of HLA-DR alleles for susceptibility to rheumatoid polyarthritis in Senega 1997 Rheumatoid arthritis is the most frequent inflammatory rheumatism disease. Several studies were aimed to understand its physiopathogenesis in particular the association between some HLA-DR alleles and rheumatoid arthritis. A prospective study was carried out in 34 patients suffering from RA (30 Women and 4 men). The diagnosis was clinically and radiologically made. The control group included 220 persons of which the HLA-DR distribution was known. The HLA-DRB1 alleles were typed by PCR-SSP (Sequence Specific Primers). The most frequent HLA-DR alleles found in patients group were: DR10 (85.3%), DR52 (53%), DR14 (38.2%), DR11 (26.5%), and DR13 (20.3%). A significant difference was observed between RA patients and control group for the following alleles: DR3, DR10, DR18, and DR52 (p < 0.001; Chi square with Yates' correction). HLA-DR3 and DR10 were positively associated with RA. The relative risk was up 30 for DR10.
11409143 Evaluating severity and status in rheumatoid arthritis. 2001 Jun There is general agreement regarding the most appropriate examinations and methods to use to evaluate change in status in randomized controlled trials (RCT). However, no guidelines exist to aid in determining and evaluating actual status rather than change in status, particularly when applied to individual patients with rheumatoid arthritis (RA). In addition, methods appropriate for clinical trials may not be useful in evaluating individual patients because of time constraints. This report reviews current methods of evaluation and develops modified methods, based on data bank research that will be useful in clinical practice and in the evaluation of RCT and observational studies. Using data from longitudinal observational data banks, further reduction in the number of joints examined is evaluated to reconcile the time constraints of clinical practice with the need to maintain reliability and validity. Percentile methods to determine severity status are applied to the variables used in RCT and extended further to observational studies and routine clinical practice. Shortened joint counts, based on modifications of the Ritchie method, are identified that allow for examination of groups of 18 (clinical-18) and 16 (clinical-16) joints, the clinical-16 omitting the metatarsophalangeal joints. Using percentile charts, actual severity valuations are given to the variables evaluated in the clinic as well as in RCT. Disease activity status of clinic patients can be determined quantitatively thus allowing clinicians further insight into the status and prognosis of their patients. By quantifying disease activity severity, clinicians and 3rd party payers can better evaluate the appropriateness of and response to disease modifying antirheumatic drugs and biologic therapies. Further, RCT can be evaluated as to severity status of patients participating, and the generalizability of RCT can be better evaluated.
10332968 Behavioral coping and physical functioning: the effect of adjusting the level of activity 1999 May OBJECTIVE: To assess the relationship between behavioral coping and dexterity in rheumatoid arthritis (RA) after controlling for disease activity, impairment of the hands, and pain. METHODS: A random sample of 109 patients with RA was assessed twice within one year. Dexterity, disease activity, and impairment of the hands were measured using observational methods. Pain and coping with RA were assessed using self-report instruments. RESULTS: Correlational findings showed that "decreasing activity" to cope with pain was negatively related to dexterity. "Pacing" as a way of coping with limitations was positively related to dexterity. Both relations were significant after controlling for duration of disease, impairment of hands, disease activity, and pain. "Decreasing activity" as a way of coping with pain was related to a decrease in dexterity in the subsequent year, after controlling for baseline measurements of dexterity, impairment, and disease activity as well as measurements of current disease activity and pain. "Pacing" as a way of coping with limitations was unrelated to subsequent changes in dexterity, after controlling for the above mentioned variables. CONCLUSION: Behaviorial coping is related to current and subsequent levels of dexterity. Therefore, it is concluded that more attention should be given to behaviorial coping in both research and clinical practice.
10725061 The links between joint damage and disability in rheumatoid arthritis. 2000 Feb OBJECTIVE: The characteristic joint damage and disability of rheumatoid arthritis (RA) increase slowly over 10-20 yr. Although it is generally believed that persisting inflammatory synovitis causes joint damage and subsequent disability, the strength of their relationship has not been systematically evaluated. This review describes their progression and interrelationship in treated RA. METHODS: MEDLINE and Current Contents databases were searched for the combined terms of rheumatoid arthritis AND X-rays, Health Assessment Questionnaire, slow-acting anti-rheumatic drugs and all identifiable synonyms. This search identified 1303 articles and from these we evaluated in detail 23 reports on the progression of joint damage, 12 reports on the progression of disability and 25 reports dealing with their interrelationship. Additional information was obtained from four data sets comprising 725 RA patients studied cross-sectionally and 33-126 cases followed prospectively for 1-5 yr. X-ray damage was primarily assessed by Larsen and Sharp indices, and disability by the Health Assessment Questionnaire (HAQ). RESULTS: Joint damage and disability both increase throughout the duration of RA. Although disability (HAQ score) is correlated with disease duration (correlation coefficients between 0.27 and 0.30), the link between X-ray damage and disability is stronger (correlation coefficients between 0.30 and 0.70). In the earliest phases of RA, X-ray damage and HAQ scores are not related. By 5-8 yr, there are significant correlations with correlation coefficients between 0.30 and 0.50. In late RA (>8 yr), most studies show highly significant correlations between 0.30 and 0.70. CONCLUSIONS: Joint damage progresses constantly over the first 20 yr of RA. It accounts for approximately 25% of disability in established RA. The link between damage and disability is strongest in late (>8 yr) RA. However, avoiding or reducing joint damage in both early and established/late RA is likely to maintain function.
10556267 Larsen scoring of digitized X-ray images. 1999 Nov OBJECTIVE: To determine how Larsen scores from digitized X-rays compare to those from film originals. METHODS: A hundred sets of radiographs of patients recruited with early rheumatoid arthritis (RA) were assessed using the Larsen scoring system. Digitized copies of these sets were then viewed on a computer screen and scored according to Larsen in a random order. The quality of the digitized image was also recorded. For each set of X-rays, the signed difference between the score from film and the score from the digitized images was calculated. RESULTS: A total of 95% of the digitized X-ray sets were scored successfully; 5% were not scored due to the images being unreadable. The mean difference between the two sets of scores was -1.2 (95% CI [-2.06, -0.37]). There was no trend in the difference with respect to the mean of the two scores (P>0.1). CONCLUSION: The Larsen scoring of digitized X-ray images has been validated.
9361165 Perioperative use of methotrexate in patients with rheumatoid arthritis undergoing orthope 1997 Nov Methotrexate (MTX) is commonly prescribed for the treatment of rheumatoid arthritis. Its use seems to be an independent risk factor for infection with common pathogens and opportunistic organisms. Some rheumatologists and orthopedic surgeons hold the opinion that MTX should be temporarily withheld to lessen the likelihood of postoperative infection or poor wound healing. Alternatively, some clinicians believe that MTX should be continued throughout the perioperative period to avoid flares in rheumatoid arthritis disease activity. There are no definitive studies on which to rely in this decision-making process, but the authors believe that withholding MTX for 2 weeks of the perioperative period is a reasonable and prudent approach.
9494989 Rheumatoid arthritis of the wrist and hand. 1998 Feb A complete assessment of the entire patient along with a clear understanding of the progression of rheumatoid deformities is the key to success when contemplating surgical intervention for rheumatoid arthritis of the hand. The decision to perform surgery must be made following careful evaluation of the patient's signs and symptoms weighed against the potential benefits likely to be gained. The surgical plan will vary from patient to patient and should be tailored accordingly. Early in the disease process, conservative measures including pharmacologic intervention, steroid injections, and hand therapy, including splinting and wrist use modification, are indicated. Surgical intervention, however, should not be avoided for so long that the benefit of successful intervention is diminished. Hand surgery has proven to be effective in correcting deformity and maintaining or increasing function in patients with rheumatoid arthritis. The indications for synovectomy, tenosynovectomy, tendon repair or realignment, arthroplasty, and arthrodesis have been well established. Superior results are possible when surgical reconstruction is performed before tendon rupture, severe fixed contractures, subluxation, or dislocation.
11465702 Treatment of rheumatoid arthritis with total lymphoid irradiation: long-term survival. 2001 Jul OBJECTIVE: Total lymphoid irradiation (TLI) has been used to treat rheumatoid arthritis (RA) since the 1970s. This study reviews long-term (15-20-year) mortality outcomes of patients treated with TLI for RA at Stanford University Medical Center and compares these outcomes with those in patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: Fifty-three patients with RA were treated with full-dose TLI at Stanford University Medical Center. All had failed previous therapy with gold salts and penicillamine. One hundred six control patients were selected from the Arthritis, Rheumatism, and Aging Medical Information Systems database and were matched with the patients for age, sex, disease duration, and mean Health Assessment Questionnaire (HAQ) score. Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: No significant difference in age and sex was found between TLI-treated patients and controls. TLI-treated patients had more education (mean 13.4 years versus 11.8 years; P = 0.016) and received more DMARDs prior to TLI (mean 2.1 versus 1.3; P = 0.0001). TLI-treated patients had lower mean HAQ scores at the time of TLI (2.0 versus 2.4; P = 0.0002). TLI had no significant overall effect on survival in treated patients compared with controls (P = 0.62). The survival curves appeared to cross over at approximately 11 years of followup, with better early survival in the TLI group and better late survival in the control group. There was a total of 25 deaths in the TLI group. There were 45 deaths in the control group, with causes of death available for 20 patients. There were 3 patients with lymphoma and 2 with myelodysplastic syndrome in the TLI group, and none in the control group. The most common cause of death in both groups was infection. CONCLUSION: TLI had no significant effect on overall survival, with trends toward higher early mortality in controls and trends toward higher late mortality in TLI-treated patients. Overall, there was no difference in mortality, but it appears that there may have been more lymphoproliferative malignancies in the TLI cohort. We would recommend that TLI be used cautiously for patients with refractory RA in whom the benefits outweigh the risks.
11396092 The epidemiology of rheumatoid arthritis. 2001 May Studies of the descriptive epidemiology of RA indicate a population prevalence of 0.5% to 1% and a highly variable annual incidence (12-1200 per 100,000 population) depending on gender, race/ethnicity, and calendar year. Secular trends in RA incidence over time have been shown in several studies, supporting the hypothesis of a host-environment interaction. People with RA have a significantly increased risk of death compared with age- and sex-matched controls without RA from the same community. The determinants of this excess mortality remain unclear; however, reports suggest increased risk from gastrointestinal, respiratory, cardiovascular, infectious, and hematologic diseases among RA patients compared with controls. Despite extensive epidemiologic research, the etiology of RA is unknown. Several risk factors have been suggested as important in the development or progression of RA. These include genetics, infectious agents, oral contraceptives, smoking, and formal education. Epidemiologic research is an essential contributor to our understanding of RA.
10412569 A role for angiogenesis in rheumatoid arthritis. 1999 May Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by distinct autoimmune, inflammatory and fibrovascular components which lead to synovial proliferation and joint destruction. However, existing treatments specifically target only autoimmune and inflammatory components despite the fact that neovascularization of the inflamed synovium is a hallmark of rheumatoid arthritis. Angiogenesis may contribute to synovial growth, leukocyte recruitment and tissue remodeling, thus potentiating disease progression. Although no therapies currently target angiogenesis, several existing therapies have anti-angiogenic activity. Recent advances in anti-angiogenic strategies in oncology, including the identification of integrin alpha v beta 3 as a crucial effector of angiogenesis, suggest a means to assess the role of angiogenesis in rheumatoid arthritis. Synovial endothelial cells have been shown to express integrin alpha v beta 3, suggesting that these cells may be targeted for angiogenesis inhibition. Prior studies in rat arthritis models have shown benefit after the addition of broad spectrum integrin antagonists. However, formal assessment of integrin-targeted anti-angiogenic activity is now underway. These controlled studies will be important in assessing the efficacy of therapies which target angiogenesis in RA.
11163080 HLA class II association with rheumatoid arthritis: facts and interpretations. 2000 Dec We have reviewed the literature on the association of HLA class II with rheumatoid arthritis (RA). Strong linkage disequilibrium among DQB1, DQA1 and DRB1 alleles makes it difficult to evaluate the individual contribution of each locus. Nonetheless, there is a strong case for the role of DQB1*03 and *04 combined with DQA1*03 in susceptibility to severe RA while DQB1*0501 combined with DQA1*0101 and *0104 weakly predisposes to a mild form of RA. However, it is also clear that DRB1*0401 has a particular role in predisposition to the most severe form of the disease while other DRB1 alleles might provide protection. We would like to propose that in RA, as in type I diabetes, both DQ and DR loci contribute to predisposition to the disease.
11501719 Health care utilization among rheumatoid arthritis patients referred to a rheumatology cen 2001 Aug OBJECTIVE: To quantify the utilization of health care by rheumatoid arthritis (RA) patients and to estimate the contribution of patient characteristics to the explanation of the use of care, in order to evaluate whether those in need of care actually receive care. METHODS: A questionnaire survey and a clinical examination were conducted among patients with RA referred to a rheumatology center. Health care utilization was assessed for medical care, allied health care, psychosocial care, and home care. The influence of sociodemographic variables and clinical and health characteristics on health care utilization was assessed by means of logistic regression. RESULTS: Multivariate analyses showed that, for all types of services, disease-related factors explained most of the utilization. However, some sociodemographic variables (age, sex, and living situation) were also related to the utilization of care. CONCLUSION: Most patients received the care they needed. However, for the elderly with RA, problems in access to allied health care and psychosocial care exist.
11165947 Bone mass changes of tibial and vertebral bones in young and adult rats with collagen-indu 2001 Jan To study the effect of arthritis on bone mass, bone mineral density (BMD) of cancellous and cortical bone in the tibial metaphysis and diaphysis in 2- and 7-month-old rats with collagen-induced arthritis (CIA) was serially measured using peripheral quantitative computed tomography (pQCT). BMD in the fourth lumbar vertebra in 7-month-old CIA rats was also measured by pQCT. The fourth lumbar vertebral body, distal femur, and proximal tibia in 7-month-old CIA rats were analyzed histomorphometrically. Changes in BMD differed between 2-month-old (young) and 7-month-old (adult) CIA rats. Although the BMD for the proximal tibia (2 mm and 5 mm distal from the growth cartilage) in young CIA rats decreased compared with that in control rats, the values exceeded the initial value during the arthritis course. On the other hand, bone loss in adult CIA rats occurred predominantly in the cancellous bone of the periarticular region of the tibia (2 mm distal from the growth cartilage), in which the enhancement of bone resorption and reduced bone formation were observed histomorphometrically. No remarkable changes were demonstrated in BMD or histomorphometrical analysis for the lumbar vertebra during the experimental course. These results suggest that bone loss in adult CIA rats resembles the osteoporosis that develops during the early stage of human rheumatoid arthritis. We conclude that adult CIA rats are more appropriate than young CIA rats as an experimental model of secondary osteoporosis due to rheumatoid arthritis.
11358421 What are the costs to society and the potential benefits from the effective management of 2001 Mar Rheumatoid arthritis is a chronic disabling condition associated with a significant long-term loss of function and a significant socio-economic impact on individual sufferers and their families, as well as on society as a whole. There is a suggestion that the incidence and severity of the disease may be abating slightly, which has been attributed to the trend to 'invert the pyramid' and to diagnose and treat rheumatoid disease earlier and more aggressively. Studies have confirmed that the erosions, which lead to subsequent joint damage, occur early in the course of the disease. Ongoing disease activity, both clinically and serologically, has now been linked to increasing morbidity, loss of function and mortality. New agents have been developed and, together with combinations of old and new agents, have been shown to be more effective if used earlier in the course of the disease. The better the early control of the disease, the better the long-term outcome. Early and more vigorous treatment, particularly of those patients with a high joint count, early loss of function and an elevated titre of inflammatory markers, has potential to reduce the twofold increase in mortality seen among rheumatoid arthritis patients. The scene is set to have a greater impact on the long-term disability and associated cost to the individual and society by treating early and treating often. Combination therapy and the new 'biologicals' are, however, far more expensive than the previously available agents, and the direct medical costs associated with medication, as well as the monitoring costs for rheumatoid arthritis, are increasing. It is difficult to value the long-term prevention of pain and suffering, and the maintenance of productivity. However, if the disease were effectively controlled early, there would be long-term benefits to be offset against the higher treatment cost. It behooves the rheumatological community to use the new agents wisely to gain the greatest advantage for all patients as well as to monitor the long-term benefits and drawbacks so that cost-effectiveness can be comprehensively evaluated.
9133935 The relationship between synovitis and erosions in rheumatoid arthritis. 1997 Feb If clinically evident synovitis causes erosions, then the two should be highly correlated within individual joints. Separate hand joints (total 2064) were examined for the presence of synovitis (the simultaneous presence of soft-tissue swelling and tenderness) on nine occasions over 2 yr. The cumulative synovitis score was compared to the change in the Larsen score over the same period. The mean correlation between synovitis and erosion progression was r = 0.248 (explained variance = 6%). Of the 216 joints which showed progressive X-ray damage, 44% had a cumulative synovitis score of < 3. When all the joints of one hand were taken together, the correlation was increased to r = 0.418 and for all the joints of both hands taken together it was further increased to r = 0.424. These results argue against there being a direct causal relationship between clinically inflamed synovitis and erosions in rheumatoid arthritis, and question the assumption that erosions and the signs of synovitis represent the same pathological process.
9246985 Shoulder hemiarthroplasty in rheumatoid arthritis. 19 cases reexamined after 1-17 years. 1997 Jun We reexamined 19 shoulder hemiarthroplasties in patients with rheumatoid arthritis after a mean of 8 (1-17) years. For the evaluation, we used the Constant and Murley score and routine radiographs. At the follow-up examination, 12 of the 19 shoulders showed little, if any, pain. In 7 shoulders the pain was moderate and no patient had severe pain. The range of motion was not improved. In 7/18 shoulders proximal subluxation of the head of the humeral prosthesis and in 9/15 shoulders, progression of the glenoid erosion were seen. The increase in glenoid erosion and the postoperative pain were not correlated. Hemiarthroplasty of the shoulder effectively relieves the pain in rheumatoid patients and this seems long-lasting.
10577301 Combination therapy with multiple disease-modifying antirheumatic drugs in rheumatoid arth 1999 Nov 16 The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.
11132204 Predictors of extra-articular manifestations in rheumatoid arthritis. 2000 OBJECTIVE: To identify clinical and genetic risk factors for extra-articular manifestations of rheumatoid arthritis (ExRA). METHODS: ExRA patients were identified retrospectively using predefined criteria in two hospital-based cohorts of RA patients, and compared to non-extraarticular RA controls from one of the cohorts, matched for disease duration. RESULTS: Forty-nine living and thirteen deceased cases of ExRA were identified. Extra-articular disease was predicted by the demonstration of antinuclear antibodies (Odds ratio (OR) 3.6; 95% CI: 1.4-9.1) and the presence of rheumatoid nodules within two years from RA diagnosis (OR 3.4; 95%, CI: 1.1-10.9) or at any time before ExRA onset (OR 2.8; 95% CI: 1.1-7.2). Male sex and rheumatoid factor did not affect the risk of ExRA. Although present in the majority of cases as well as controls, the disease associated HLA-DRB1 subtypes were not significant predictors of ExRA. CONCLUSION: Extra-articular manifestations of rheumatoid arthritis in a hospital based population were predicted by antinuclear antibodies and rheumatoid nodules.
10664422 Progression of rheumatoid arthritis of the cervical spine: radiographic and clinical evalu 1999 Cross-sectional and longitudinal studies were conducted to observe progression of rheumatoid arthritis in the cervical spine. Two hundred and ninety-seven patients were enrolled in the cross-sectional study. Both upper and lower cervical spine involvement increased with disease duration. The relationship between atlanto-axial motion and the development of subaxial subluxation was inconclusive. Eighty-seven patients were enrolled in the longitudinal study and were followed for at least 5 years. In about half of these patients, rheumatoid changes started from the upper cervical spine, with rheumatoid changes beginning from the lower cervical spine in about 8% of patients. Neurological deficits were correlated with radiographic changes but neck pain did not correlate with radiographic changes. As to the upper cervical spine, the parameter most influencing neurological deficits was found to be the minimum value of the atlanto-axial angle in flexion, by multivariate analysis using a multiple logistic model. Neurological deficits were seen in more than half the patients when the atlanto-axial angle in flexion was 5 degrees or less.