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ID PMID Title PublicationDate abstract
14535175 TCM treatment for 40 cases of rheumatoid arthritis with channel blockage due to yin defici 2003 Sep To verify the therapeutic effects of the method of softening and lubricating the joints, and calming the endogenous wind in case of rheumatoid arthritis (RA) with the syndrome of channel blockage due to yin deficiency, 60 RA patients with the syndrome of channel blockage due to yin deficiency were randomly divided into a treatment group (40 cases) and a control group (20 cases) and treated respectively by the above method for the former and with Zheng Qing Feng Tong Ning Tablets ([symbol: see text]) for the latter. The result turned out to be that the effect in the treatment group was very satisfying. The treatment group obtained a better result in the accumulated points of syndrome and RA, morning rigidity of the joints, grip strength, 20m walking time and erythrocyte sedimentation rate (ESR) (P < 0.01 or P < 0.05). The above indicates that channel blockage due to yin deficiency is an important pathogenesis of RA, and calming the endogenous wind is a method of choice for treating RA.
15010161 Radiographic changes after resection of the distal ulna in rheumatoid arthritis. 2004 Apr Progressive ulnar translocation of the carpus and problems with the ulnar stump have been reported after resection of the distal ulna in rheumatoid arthritis (RA). However this has only occasionally been quantitatively assessed. In this study 24 wrists in 21 patients with RA were followed up for an average of 100 months after resection of the distal ulna. An additional 24 wrists in 14 non-operated RA patients were followed up for 92 months. In a retrospective radiographic analysis we demonstrate similar increases in ulnar translocation and ulnar-carpal distances in both groups.
12739047 A challenging case of rheumatoid arthritis in an acromegalic patient. 2003 May A 63-year-old man with complaints of joint pain and ankle swelling was evaluated. The arthralgias he described were mainly in the knees, elbows, and shoulders. Accompanying swelling and erythema in his left ankle and left second metacarpophalangeal (MCP) joint had recently ensued. His past history revealed acromegaly, somatotropinectomy, and radiotherapy. His neck, bilateral wrist, elbow, and shoulder joints were involved; there was pain and limited range of motion. The MCP joints, being worse than the interphalangeal joints, were likewise involved. His left ankle and MCP joints additionally were swollen and erythematous. Laboratory and radiological evaluations were carried out. Radiological and clinical findings confirmed a diagnosis of rheumatoid arthritis and concurrent acromegalic arthropathy. The patient was treated accordingly. Interestingly, he later developed colon cancer.
14969059 The Leiden Early Arthritis Clinic. 2003 Sep In 1993 a special Early Arthritis Clinic (EAC) was established at the Department of Rheumatology of the Leiden University Medical Center in order to detect and treat inflammatory disorders early in the disease state, especially early rheumatoid arthritis. Patients with confirmed arthritis of recent onset (less than 2 years) were included by rheumatologists and trained research nurses. Parameters of first and follow-up visits (3, 6 and 9 months and yearly) that were entered in the EAC-database include the medical history, physical-diagnostic examination, laboratory tests, questionnaires, radiographic joint scores and diagnosis. This database enables us to conduct research on arthritis, with an emphasis on rheumatoid arthritis, in many ways. Physicians and basic scientists have studied cellular immunology and genetic, environmental and clinical risk factors in order to determine the pathophysiologic mechanisms of inflammatory arthritis. The present article is a review on reports published from the EAC. Over the past ten years, these reports have been highly relevant for both daily clinical practice and research. Present and planned future studies, as described in this article, reconfirm the importance of an EAC framework to ensure that research continues on this disease in the Leiden EAC area.
15201942 [IL-1Ra (recombinant human IL-1 receptor antagonist) in the treatment of rheumatoid arthri 2004 Jan Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA). In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX); the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20), compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ) were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN) and the Total modified Sharp-Genant score (a combination of erosion and JSN) in all treatment groups (30,75 and 150mg/day). The clinical benefits of treatment with daily subcutaneous injections of IL-1ra in active RA patients were maintained for up to 48 weeks. IL-1ra, a selective inhibitor of the IL-1 pathway, represents an important new biologic approach to treating patients with RA, that significantly reduces clinical signs and symptoms of the disease and joint destruction and has proved safe and well tolerated also in combination with other DMARDs and concomitant medications.
13679737 [Total elbow arthroplasty in rheumatoid arthritis using GUEPAR prosthesis]. 2003 Sep PURPOSE OF THE STUDY: We report a retrospective analysis of 16 patients with rheumatoid arthritis treated with a total humero-ulnar and humero-radial GUEPAR prosthesis (GIII). MATERIAL AND METHODS: The GUEPAR III elbow prosthesis is an anatomic polyethylene-metal gliding prosthesis designed to maintain physiological valgus. Right and left models are available in two sizes. On the humero-ulnar side of the prosthesis, was associated with a radial head, born on an intramedullary metallic stem, that can be fit with several sizes of mobile polyethylene cups. The 16 GIII prostheses were implanted in 1997 to 2001 in accordance with the manufacturers instructions. Mean follow-up was 2 years. RESULTS: Before surgical treatment, all patients had moderate or severe but invalidating pain. The Mayo Clinic score was 33 points. The Larsen radiographic score was grade III (7 elbows) or grade IV (9 elbows). Patients were reassessed 1 to 5 years after implantation of the GIII (mean follow-up 2 years). At last follow-up the mean Mayo Clinic score had improved from 33 to 90 points. Outcome was considered excellent for 15 elbows and fair for 1. DISCUSSION: We review the indications for total elbow arthroplasty in patients with rheumatoid arthritis. Semi-constrained prostheses are useful and necessary for the treatment of elbows exhibiting massive destruction, but the use of minimally constrained prostheses such as the GUEPAR III is becoming increasingly widespread. We use the GUEPAR III for 70% of our patients, particularly those with rheumatoid arthritis.
14673963 Spirituality, well-being, and quality of life in people with rheumatoid arthritis. 2003 Dec 15 OBJECTIVE: To evaluate spirituality, well-being, and quality of life (QOL) among people with rheumatoid arthritis (RA). METHODS: Questionnaires assessing positive and negative affect, depression, QOL and spirituality were completed. Disease activity was assessed by rheumatologic examination. RESULTS: Women (n = 62) had a mean (+/- SD) age of 53.0 (+/- 13.0) years with 12 (+/- 13) swollen and tender joints (STJ). Men (n = 15) were 61.9 (+/- 13.0) years with 7 (+/- 11) STJ. Disease activity was associated (P < 0.05) positively with depression (r = 0.23), pain (r = 0.26), poorer self-ratings of health (r = 0.29) and physical role limitations (r = 0.26). Spirituality was associated directly with positive affect (r = 0.26) and higher health perceptions (r = 0.29). In multiple regression, spirituality was an independent predictor of happiness and positive health perceptions, even after controlling disease activity and physical functioning, for age and mood. CONCLUSION: Spirituality may facilitate emotional adjustment and resilience in people with RA by experiencing more positive feelings and attending to positive elements of their lives.
12922955 Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from 2003 Sep OBJECTIVE: To quantify the influence of cigarette smoking on the risk of developing rheumatoid arthritis (RA). METHODS: 679 cases and 847 controls included during May 1996-June 2000 in a case-control study, using incident cases, comprising the population aged 18-70 years of a defined area of Sweden, were investigated. A case was defined as a person from the study base who received for the first time a diagnosis of RA using the 1987 American College of Rheumatology criteria, and controls were randomly selected from the study base. Self reported smoking habits among cases and controls, and rheumatoid factor status among cases were registered. The incidence of RA in current smokers, ex-smokers, and ever-smokers, respectively, was compared with that of never-smokers. RESULTS: Current smokers, ex-smokers, and ever-smokers of both sexes had an increased risk for seropositive RA (for ever-smokers the odds ratio was 1.7 (95% confidence interval (95% CI) 1.2 to 2.3) for women, and 1.9 (95% CI 1.0 to 3.5) for men), but not for seronegative RA. The increased risk was only apparent among subjects who had smoked > or =20 years, was evident at an intensity of smoking of 6-9 cigarettes/day, and remained for up to 10-19 years after smoking cessation. The risk increased with increasing cumulative dose of smoking. CONCLUSION: Smokers of both sexes have an increased risk of developing seropositive, but not seronegative, RA. The increased risk occurs after a long duration, but merely a moderate intensity, of smoking and may remain for several years after smoking cessation.
11830438 Factors related to radiological damage in 61 Spaniards with early rheumatoid arthritis. 2002 Mar OBJECTIVE: To determine whether the presence of radiographic erosions at disease onset in patients with early rheumatoid arthritis (RA) is associated with clinical, serological, or genetic factors of poor outcome and whether patients with erosions only in the feet have a different pattern of presentation. METHODS: Sixty one patients with early RA (<6 months of evolution) were studied. Clinical evaluation and serological, radiological, and genetic studies were performed at disease onset and after one year. RESULTS: Forty one (67%) patients showed erosions in their hands or in their feet, or in both. Subjects with erosive RA had a higher number of swollen joints (SJN; 9 (SD 6) v. 6 (3), p=0.008), and rheumatoid factor (RF) positivity was more common (80% v. 50%, p<0.02) than those without erosions. Seven (17%) of the 41 patients in the group with erosions had erosions only in their feet. This group had a longer duration of morning stiffness (120 (60) v. 72 (52) min, p<0.005), better patient's global assessment of general health (34 (22) v. 57 (25), p< 0.05), and lower erythrocyte sedimentation rate (32 (22) v. 60 (30) mm/1st h, p <0.05) than the rest of the subjects with erosions, and none of them was in remission after one year. Remission after one year was related to a lack of cortical damage at onset and RF negativity. CONCLUSIONS: Radiological damage at disease onset is associated with a worse clinical presentation and RF positivity, which are markers of poor outcome. There is a subgroup of patients, with erosions only in their feet, whose clinical presentation is less aggressive. To identify these cases of early erosive RA, radiographs of the feet should be obtained routinely.
15022311 Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis f 2004 Mar OBJECTIVE: In patients with rheumatoid arthritis (RA) treated with tumor necrosis factor alpha (TNF alpha)- blocking therapy, there is heterogeneity of response. This raises the possibility that in certain circumstances, cytokines such as interleukin-1 (IL-1) may dominate the drive toward joint inflammation. This study was undertaken to investigate whether blocking the action of IL-1 with an IL-1 receptor antagonist (IL-1Ra) is efficacious in patients with disease that did not respond to TNF alpha blockade. METHODS: We identified 26 RA patients whose disease had failed to respond to TNF alpha-blocking therapy, defined as failure to achieve or sustain a 20% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR20 response). These patients were then treated with anakinra (100 mg/day subcutaneously) for 12 weeks, and their levels of response were assessed. RESULTS: After 3 months of anakinra therapy, only 2 of 26 patients (8%) achieved an ACR20 response; none achieved an ACR50 or ACR70 response. A rise in the mean C-reactive protein level and an increase in the mean swollen joint count were noted during the study period. CONCLUSION: This study demonstrates that patients with disease that fails to respond to TNF alpha blockade also do not respond to IL-1Ra. These data do not provide evidence of a dominant role for IL-1 in patients who do not respond to TNF alpha blockade, but they do not exclude a role for other proinflammatory mediators.
16722900 Rheumatoid arthritis-associated inflammatory leg ulcers: a new treatment for recalcitrant 2004 Apr Patients with rheumatoid arthritis may develop leg ulcers of varied aetiologies, including venous disease, infection and inflammation (vasculitis or pyoderma gangrenosum). The leg ulcers in rheumatoid arthritis patients may involve several of these aetiological factors and are often difficult to heal. Both the ulcers and the treatments are often painful, and these ulcers may be present for years. A new oxidised regenerated cellulose and collagen dressing has been developed for slow-to-heal wounds and may have a role in the management of superficial inflammation that may persist in many of these ulcers, although clinically it is difficult to distinguish this from critical colonisation or frank infection. Venous disease requires compression therapy. Deep compartment infection should be treated with systemic antimicrobials, and inflammatory processes extending beyond the superficial wound base require disease-specific systemic anti-inflammatory agents. Four patients with recalcitrant wounds resistant to best practice were treated successfully with this new dressing combined with a strategy to control bacterial burden.
12368374 Imaging cell death with radiolabeled annexin V in an experimental model of rheumatoid arth 2002 Oct Rheumatoid arthritis is associated with chronic synovial inflammation due to the abnormal accumulation of macrophages and autoreactive T lymphocytes in joints. The autoreactive cells cause an inflammatory proapoptotic response to self-antigens resulting in eventual bone, cartilage, and soft-tissue loss and destruction. The goal of our study was to determine the timing and intensity of apoptosis in joints using 99mTc-labeled annexin V, an in vivo marker of apoptosis, in a murine model of immune arthritis. METHODS: We used 99mTc-annexin V and autoradiography to study the extent and severity of apoptosis in the front and rear paws of DBA/1 mice with type II collagen-induced rheumatoid arthritis. RESULTS: Compared with control values (n = 10), there was a significant (P < 0.002) nearly 3-fold increase in uptake of 99mTc-annexin V in the front foot pads, rear toes, rear foot pads, and heels at the time of maximal extremity swelling as determined by serial caliper measurements at 4 wk after inoculation with type II bovine collagen (n = 9). The front toes had a 5- to 6-fold increase in uptake compared with control values (P < 0.001). Histologic analysis revealed only scattered rare lymphocytes in the periarticular soft tissues, without joint destruction. Dual autoradiography with 125I-bovine serum albumin as a control showed that 99mTc-annexin V localization was specific. Treatment with methylprednisolone for 1 wk (n = 8) at 4 wk after immunization with type II collagen decreased 99mTc-annexin V uptake by 3- to 6-fold compared with control values (P < 0.002). CONCLUSION: 99mTc-annexin V can detect collagen-induced immune arthritis and its response to steroid therapy before joint destruction.
14596374 Investigating sleep disturbances in adults with rheumatoid arthritis. 2003 Sep Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and joint involvement. Most adults with RA experience sleep disturbances, including longer times before falling asleep, numerous awakenings during the night, and early morning wakening, resulting in excessive daytime sleepiness and fatigue. This article will review what is known about sleep disturbances and the biologic basis in adults with RA, the influence of ovarian hormone levels in women with RA, how medications may influence sleep in RA, and complementary and alternative therapies that may be useful in reducing sleep disturbances.
12695152 Applying low disease activity criteria using the DAS28 to assess stability in patients wit 2003 May OBJECTIVES: To examine whether low disease activity criteria using the disease activity score (DAS28) can be applied to identify a reasonably large number of patients with stable low disease activity of rheumatoid arthritis (RA) over a six month period, with the ultimate intention of including these patients in a substitution based, shared care model. Additionally, to assess the reliability of the DAS28 for selecting patients with stable disease from an outpatient population. METHODS: Patients regularly seen at the rheumatology outpatient department of the university hospital Maastricht, were invited for assessment of the stability of their RA. The shared care model was intended to provide care to patients with stable, low disease activity of RA by nurse specialists. For this, patients underwent assessments using the DAS28 criteria at entry and three and six months later. Test-retest reliability was assessed for composing measures as well as for the DAS28. RESULTS: Of the 97 outpatients included, one third (31 patients) did not complete the study. Patients with missing data were older and assessed their disease activity as greater than patients with complete data. Applying the low disease activity criteria to assess stability over a period of six months (DAS28(T0)
12010604 Role of nuclear factor kappaB in synovial inflammation. 2002 Jun The evaluation of molecular pathways has revealed novel insights into the pathophysiology of rheumatoid arthritis in the last several years. Gene transcription factors such as nuclear factor kB (NFkB) are activated by extracellular signals or cell-to-cell interactions that are converted into intracellular activation signals through receptor molecules located in the cell membrane. The number of known genes being translated after NFkB activation is increasing steadily. These genes includes cytokines, chemokines, growth factors, cellular ligands, and adhesion molecules. Because many of these genes are part of the pathogenesis of RA, there is considerable interest in the evaluation of the synovium-specific effects of NFkB to unveil its potential for future therapeutic strategies. The goal is to evolve these strategies from the therapies that have a wide spectrum of effects and side effects into rheumatoid arthritis-specific therapies designed to inhibit distinct molecular pathways within the synovium.
15794199 Health care costs attributable to the treatment of rheumatoid arthritis. 2004 OBJECTIVE: A 'programme budget' for the resources used in the treatment and care of patients with rheumatoid arthritis (RA) was developed with a view of helping decision-makers assess the appropriateness of the current use of resources and to discuss future resource allocation. METHOD: The programme budget was developed using data from several national administrative registers. Patients with RA were identified by hospital diagnostic codes. The incremental cost of treating RA was defined as the difference in resource use for patients with and without RA. Incremental mortality due to RA was defined in similar way. Cost data were estimated for 5-year age groups. RESULTS: Patients with RA used on average 3.2 times as many health care resources as people without RA. The average 1997 incremental costs of primary and hospital care were EUR 253 and EUR 2.660 per patient respectively, corresponding to a national incremental cost of EUR 30 million (2000 price level). RA resulted in an annual loss of 1,549 life years. CONCLUSION: The programme budget approach is a useful tool in resource allocation decision-making, but discussions of alternative resource allocations must be based on robust studies of effectiveness and cost-effectiveness in the treatment of patients with RA.
15201607 Noninvasive techniques for assessing skeletal changes in inflammatory arthritis: bone biom 2004 Jul PURPOSE OF REVIEW: Inflammatory arthritis diseases including rheumatoid arthritis (RA) are characterized by systemic bone loss and increased risk of osteoporosis and local joint bone erosion. Clinical and biologic parameters of disease activity and inflammation and radiologic findings are poorly sensitive for assessing skeletal changes. More specific biologic markers reflecting systemic quantitative and dynamic changes of bone turnover represent promising adjunctive tools. RECENT FINDINGS: More specific and well-characterized biochemical assays especially for type I collagen-based bone resorption markers have been recently developed. Prospective studies indicate that increased levels of some biochemical markers of bone resorption are associated with a more rapid progression of joint destruction in patients with early RA, independently of disease activity and inflammation parameters. This increased bone resorption associated with local bone erosion is likely to be mediated by changes in the balance of the OPG/RANK-L system (receptor activator of nuclear factor kappaB-ligand and osteoprotegerin) as suggested by the significant association of this ratio in serum and long-term radiologic progression. Besides their well-documented response to bisphosphonate treatment used as adjuvant therapy in patients with glucocorticoid-induced osteoporosis, bone markers may be useful to assess potential beneficial effects of new disease-modifying antirheumatic drugs on systemic bone loss and on progression of joint damage. SUMMARY: Recent evidence suggests that biochemical markers of bone resorption may be useful to predict progression of joint damage in RA. Together with new biochemical markers of cartilage turnover, they are likely to play a major role in assessing effects of treatment on joint damage. Their value in assessing systemic and local bone abnormalities should be explored in other inflammatory arthritis diseases such as ankylosing spondylarthritis.
12942312 The Nottingham Health Profile in rheumatoid arthritis: correlation with other health statu 2004 Jul OBJECTIVE: The overall effect of rheumatoid arthritis (RA) on general health status has drawn attention in recent years. The aim of this study was to determine the clinical relevance of the Nottingham Health Profile (NHP) in RA patients and the relationship between conventional clinical measures, the Health Assessment Questionnaire (HAQ), and the Beck Depression Inventory (BDI) METHOD: One hundred RA patients (mean age 48.9+/-12.1 years, mean disease duration 101.3+/-85.5 months) were included in the study. Quality of life, health status, and psychological mood of the patients were assessed using NHP, HAQ, and BDI. The Ritchie Articular Index (RAI), visual analog scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and modified Larsen Scale were used to assess clinical, laboratory, and radiological changes. RESULTS: All subgroups of the NHP significantly correlated to VAS, RAI, BDI, and HAQ scores (P<0.001). Except in the social isolation subgroup, there were significant correlations with ESR (P<0.05, P<0.001, and P<0.0001, respectively). There were no correlations between CRP levels and health status measures (P>0.05). CONCLUSION: The NHP reflects the clinical and psychological status of RA patients and can be used as a sensitive health status measure for clinical evaluation.
14705216 Enhanced concentrations of interleukin 16 are associated with joint destruction in patient 2004 Jan OBJECTIVE: To investigate the role of interleukin 16 (IL-16) in the development of rheumatoid arthritis (RA) and joint destruction. METHODS: We measured systemic IL-16 levels longitudinally in 39 patients with recent-onset RA, in 13 patients with initially undifferentiated arthritis who will develop RA over time, in 15 patients with undifferentiated arthritis, and in 12 healthy controls, and correlated the levels with joint damage and disease activity. Systemic IL-16 levels were measured by ELISA. Joint destruction was measured according to the Sharp method and the disease activity variables included C-reactive protein (CRP) and Disease Activity Score (DAS) measured at disease onset, and after one and 2 years of followup. RESULTS: A significantly increased IL-16 level in RA patients at disease onset [median (25th-75th percentile) 45.2 (37.7-82.4) pg/ml] was observed compared to both controls [30.4 (24.4-37.0) pg/ml, p = 0.0008], and to patients with undifferentiated arthritis [29.0 (21.5-52.4) pg/ml; p = 0.005]. The IL-16 levels of the patients who presented with undifferentiated arthritis but who developed RA over time were also increased [47.9 (34.5-108.2) pg/ml] compared to the controls (p = 0.004) and to the patients who over time remained diagnosed with undifferentiated arthritis (p = 0.01). We found that high IL-16 levels correlated positively with joint destruction during the 2-year followup (p = 0.02) and not with the disease activity variables. CONCLUSION: Our results suggest that the cytokine IL-16 plays a role in the disease process underlying RA and joint destruction.
15361376 Methotrexate related adverse effects in patients with rheumatoid arthritis are associated 2004 Oct BACKGROUND: There is an association between C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate related toxicity. OBJECTIVE: To examine the relations between the recently described A1298C polymorphism of the MTHFR gene, plasma homocysteine, methotrexate toxicity, and disease activity in patients with rheumatoid arthritis. DESIGN: A cross sectional study on 93 methotrexate treated patients with rheumatoid arthritis, comprising a clinical interview and physical examination to determine disease activity and methotrexate related adverse reactions. Genotype analysis of the MTHFR gene was carried out and fasting plasma homocysteine and serum folate concentrations were measured. The data were analysed using univariate analysis. Allele and genotype distributions were compared with those of a healthy control group. RESULTS: The frequency of the 1298CC genotype (24.7%) in the rheumatoid study group was greater than expected in the general population (12.8%, p<0.001). This genotype was associated with a significantly low rate of methotrexate related side effects. The odds ratio for side effects in patients with wild type 1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval, 1.38 to 20). No correlation of disease activity variables or plasma homocysteine with MTHFR A1298C and C677T polymorphisms was observed. CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated rheumatoid patients than expected in the population, and was associated with a reduction in methotrexate related adverse effects. The A1298C polymorphism of the MTHFR gene may indicate a need to adjust the dose of methotrexate given to patients with rheumatoid arthritis.