Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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16855148 | Epidemiological aspects of rheumatoid arthritis: the sex ratio. | 2006 Jun | Many rheumatic diseases, including rheumatoid arthritis (RA) are more frequent in females than males. The objective of this article was to examine the female versus male perspective regarding prevalence/incidence, etiological factors, disease severity/outcomes, access to therapy and therapeutic responses. We also present results from some new analyses from the patient registers in Oslo to supplement existing literature in this area. We found that the prevalence of RA is higher in females than males, the incidence is 4-5 times higher below the age of 50, but above 60-70 years the female/male ratio is only about 2. Smoking is a consistent predictor of RA in males, but findings have been more inconsistent in females. We could not confirm that health status is worse in females than males when corrections were made for different disease duration and for the underlying tendency of healthy females to report worse subjective health status than males. Some studies and data presented here indicate that females have less access to health services. We also found that female sex reduces the likelihood of achieving treatment response with methotrexate and anti-tumor necrosis factor (anti-TNF) drugs by 30-50%. More research is needed to fully describe the differences between males and females regarding epidemiological data. | |
18317879 | Life expectancies of Japanese patients with rheumatoid arthritis: a review of deaths over | 2008 | We investigated trends in life expectancy in rheumatoid arthritis (RA) patients, reviewing records for 286 patients (204 female, 82 male) who had died over the past 20 years. The average age at death was 68.8 years before 1990, increasing to 72.1 years after 2001. Trends in disease modifying anti-rheumatic drugs (DMARDs) saw gold preparations (45.2%) predominate before 1990, sulphydryl donor agents (53.6%) from 1991 to 2000, then methotrexate (43.0%) after 2001. The most common causes of death were infectious diseases up to 1995, rheumatic disease 1996-2000, and cardiovascular events and malignancies after 2001. Major advances in surgical interventions, such as joint replacement surgery, occurred after 1990. Surgical intervention followed by a period of rehabilitation maintained a favourable level of activities of daily living (ADLs), The requirements for favourable life expectancy are control of RA inflammation and maintenance of a favourable level of ADLs. Although recently developed DMARDs and biological agents show promise, caution is required to avoid serious adverse reactions. Optimum care of patients with RA will require preventive measures and early intervention for infections and rheumatic diseases, as well as for lifestyle diseases, osteoporosis and malignancies. | |
17937474 | Association of anemia and physical disability among patients with rheumatoid arthritis. | 2007 Nov | OBJECTIVE: To evaluate the relationship between hemoglobin concentration and physical disability in patients with rheumatoid arthritis (RA). METHODS: Data were derived from 2495 patients with RA enrolled in 3 clinical trials (ATTRACT, ASPIRE, and START) and treated with infliximab (3 to 10 mg/kg) plus methotrexate (MTX), or MTX plus placebo. The association of hemoglobin and the Health Assessment Questionnaire (HAQ) score was assessed at baseline (n = 2471) and Week 22 (n = 2458) by Spearman correlation, and multivariate linear regression models were employed to control for confounding effects from demographic and other clinical variables. A logistic regression model was used to estimate the odds ratio (OR) for a clinically meaningful improvement (> or = 0.25 point increase) in HAQ associated with a > or = 1 g/dl improvement in hemoglobin from baseline at Week 22. RESULTS: About 37% of patients with RA had anemia based on World Health Organization criteria: hemoglobin < 12 g/dl in women (39%) and < 13 g/dl in men (32%). Low hemoglobin level was significantly associated with more severe physical disability at baseline (p < 0.001), and both male and female patients with anemia had more severe disability at baseline. Improvement in hemoglobin after treatment at Week 22 was an independent contributor to improvement in HAQ, and a > or = 1 g/dl improvement in hemoglobin after treatment was associated with a clinically meaningful improvement in the HAQ score at Week 22 (OR 1.43, 95% CI 1.10-1.86; p < 0.01). CONCLUSION: Anemia is one of the independent factors contributing to physical disability in patients with RA. Improvement in anemia following effective RA treatment may play an independent role in improving physical function. | |
18414965 | The place of methotrexate perioperatively in elective orthopedic surgeries in patients wit | 2008 Oct | No clear consensus exists on whether methotrexate (MTX) should be continued or whether this therapy should be discontinued for a few weeks in patients with rheumatoid arthritis (RA) undergoing surgery. Continued MTX therapy may impair wound healing, but discontinuation of the therapy may increase the risk of flares. In this article we review published data on the perioperative management of MTX in patients with RA undergoing elective orthopedic surgery. Eight papers on this topic could be identified. These studies compare continued vs. discontinued MTX therapy or MTX therapy vs. therapies other than MTX. Summing up the published data, continued MTX therapy appears to be safe perioperatively and seems also to be associated with a reduced risk of flares. None of the examined papers addresses the issue of safety in connection with comorbidities, age or high doses of MTX. | |
18081549 | Rheumatoid arthritis treatment and monitoring of outcomes--where are we [corrected] in 200 | 2007 | Rheumatoid arthritis (RA) treatment has witnessed major advances over the last 10 to 20 years. Methotrexate has emerged as the cornerstone of treatment with new biologic agents being used in addition in severe and resistant patients. New drugs being developed with novel modes of action are promising to expand treatment options and help provide better disease control for RA patients. In addition to medications, equally important is aggressive disease activity monitoring using one of the composite scores available in order to match treatments to disease activity. Disease activity score (DAS), DAS28 (with a 28 joint count), clinical disease activity index (CDAI), simplified disease activity index (SDAI), and routine assessment of patient index data (RAPID) are valuable tools and should be used in routine care to achieve disease control. | |
16652419 | Patient's ethnicity does not influence utilization of effective therapies in rheumatoid ar | 2006 May | OBJECTIVE: Biological agents have revolutionized the treatment of rheumatoid arthritis (RA). Given the previously documented ethnic disparity in the health service literature, we sought to determine if ethnic difference exists in the lag time between the diagnosis of RA and use of first biological agent. METHODS: RADIUS 1 and 2 are observational studies designed to document how rheumatologists treat RA across the United States. The sample analyzed here included early patients with RA who entered RADIUS with the initiation of the first biological agent. Ethnic status was categorized as White (W), African American (AA), and Hispanic (H). Lag time (months from RA diagnosis to initiation of the first biological agent) was the principal outcome variable. RESULTS: Compared to W (n=1616), AA (n=147) and H (n=116) were more likely to be female, younger, and have less than a high school education. Despite similar swollen and tender joint counts, AA and H had more active disease on the basis of Health Assessment Questionnaire and patient global assessments. Almost 97% of patients had some type of insurance coverage. On multivariable analysis, ethnic affiliation was not associated with lag time (14.5 months W vs 14.9 AA vs 14.3 H; p=NS). Similarly, there were also no significant ethnic differences in time to first DMARD (e.g., methotrexate) initiation. CONCLUSION: In a national sample of patients with RA, most of whom were insured, the length of time from diagnosis of RA to initiation of the first biological agent was not significantly different among Whites, African Americans, and Hispanics. | |
16374576 | Efficacy of arthroscopic synovectomy for the effect attenuation cases of infliximab in rhe | 2006 Nov | To investigate whether arthroscopic synovectomy is effective for nonresponders to infliximab, anti-tumor necrosis factor-alpha antibody, for the treatment of rheumatoid arthritis (RA), we assessed seven patients including ten arthroscopic synovectomies in knee joint, in shoulder joint, and in ankle joints. We compared C-reactive protein (CRP) and DAS28 (ESR) before and after surgery at 6 and 50 weeks. After arthroscopic synovectomy, we continued the infliximab treatment with methotrexate in a routine manner. We detected synovium proliferation with vascular increase in patellofemoral joint and around the meniscus and femoral and tibial side of the anterior cruciate ligament in the knee joints. We also found synovial proliferation in rotator interval in the glenohumeral joint and fatty changing in subacromial bursa in the shoulder. In the ankle joint, we found synovial proliferation with white meniscoid between tibiofibular joint to develop impingement. Serum CRP was improved from 3.45+/-0.4 to 1.12+/-0.2 at 6 weeks to 1.22+/-0.4 at 50 weeks after arthroscopic synovectomy. There is no severe side effect of arthroscopic synovectomy during infliximab treatment; however, one patient had slight rash that was improved. DAS28 was improved from 5.58+/-0.23 to 3.87+/-0.47 at 6 weeks to 2.58+/-1.49 at 50 weeks after arthroscopic synovectomy. It is possible that arthroscopic synovectomy can be one of the effective methods to continue with the infliximab treatment when its efficacy decreased or in the nonresponders of infliximab for RA patients. | |
19371393 | Treatment-induced stable, moderate reduction in blood cell counts correlate to disease con | 2009 May | BACKGROUND: Treatment of rheumatoid arthritis (RA) has become more intensive, thereby raising concerns regarding toxicities, including leucopenia. The objective was to analyse cell counts obtained as routine surveillance for adverse effects to assess the effect of intensive treatment and treatment dosage and to examine correlations to disease activity scores. METHODS: Patients with early RA were treated with combinations of disease-modifying anti-inflammatory drugs according to pre-defined rules, with dose adjustments contingent on residual disease activity and tolerance. RESULTS: Mean leucocyte, neutrophil and platelet counts fell with levels that correlated to disease activity scores. The strongest correlation was between platelets and disease activity scores. There was a modest, inverse correlation between methotrexate dose and monocyte and lymphocyte counts. No serious toxicity associated with the therapy was seen. CONCLUSION: Moderate reductions in cell counts are well tolerated in RA and appear to contribute to disease control. | |
17412740 | QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in s | 2007 Nov | OBJECTIVE: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. METHODS: The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. RESULTS: Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 |
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16429237 | Remission of rheumatoid arthritis after acute disseminated varicella-zoster infection. | 2007 May | A 65-year-old immunocompetent male presented with symmetric polyarthritis of 12 weeks and paresthesias in the distribution of the left median nerve distribution of 4 weeks duration. He had tender joint count of 20 and swollen joint count of 12. He was positive for rheumatoid factor and his erythrocyte sedimentation rate was 52 mm. Nerve conduction study demonstrated polyneuropathy. Radiographs showed severe juxta articular osteopenia at the wrist and the metacarpophalangeal joints. He received methotrexate of 10 mg/week and prednisolone of 0.15 mg/kg/day along with nonsteroidal antiinflammatory drugs (NSAIDs) with a diagnosis of seropositive rheumatoid arthritis (RA). Thirteen weeks after therapy, he presented to the outpatient clinic with disseminated vesicular eruptions all over his body with erythematous base and pneumonia involving the left upper lobe. Tzanck smear from the lesions and serology (IgG) for varicella-virus infection were positive. A diagnosis of acute disseminated varicella zoster with pneumonia was made. The patient improved on parenteral acyclovir and broad-spectrum antibiotics. With the improvement in rash and pneumonia after 2 weeks, the patient noticed a marked improvement in the joint symptoms. Arthritis remained in remission without the need for any disease-modifying drug or NSAID for next the 24 months and continued to be so until the last follow-up. Our case presents a unique phenomenon of RA remission after disseminated varicella-zoster infection in an immunocompetent individual. | |
16531550 | Going with the flow: methotrexate, adenosine, and blood flow. | 2006 Apr | Methotrexate treatment modulates adenosine metabolism in patients with rheumatoid arthritis | |
17149054 | Polyarthritis flare complicating rheumatoid arthritis infliximab therapy: a paradoxic adve | 2006 Dec | BACKGROUND: The treatment of rheumatoid arthritis (RA) has changed dramatically over the past decade with the introduction of antitumor necrosis factor (anti-TNF) agents. Although subsets of patients may have only partial or no response, there is no report yet on possible worsening of RA with this therapy. OBJECTIVE: The objective of this study was to determine whether infliximab may paradoxically exacerbate RA. METHODS: One hundred seven patients with RA refractory to 3 disease-modifying antirheumatic drugs were treated with 3 mg/kg infliximab and methotrexate for at least 6 months. RESULTS: In 3 patients, there was an exacerbation of RA associated with the use of infliximab. The flare occurred during the first 6 to 12 months of treatment with polyarthritis, fever, and elevated acute phase reactants. Increase of infliximab dose resulted in further deterioration. CONCLUSION: We describe a paradoxic reaction, an exacerbation of RA, with infliximab. The mechanism of this side effect is unclear but may be related to altered immunity induced by the inhibition of TNF activity in predisposed patients. | |
17621799 | [Treatment of rheumatoid arthritis (RA) with anticytokines]. | 2006 Oct 19 | In the hands of an experienced rheumatologist and in adherence to the contraindications named in the article, anticytokines such asTNF-alpha blockers or interleukin-1 antagonists are regarded as relatively reliable, are well tolerated and in many cases, are very effective. Especially when used in combination with methotrexate, they demonstratively lower the disease activity score and significantly slow the radiographic progression.Thus, anticytokines are currently the most effective therapy for RA. An additional advantage compared to conventional DMARD is the rapid onset of action (usually within two to four weeks).TNF-alpha blockers are also presently employed in numerous other chronic inflammatory diseases. The efficacy of anticytokines in psoriasis and psoriatic arthritis, ankylosing spondylitis, juvenile arthritis and Crohn's disease has been proven. | |
16421640 | [Pneumocystis jiroveci pneumonia (PcP) in patients with rheumatic diseases: case report an | 2006 Feb | A 74-year-old female patient with rheumatoid arthritis was diagnosed with Pneumocystis jiroveci pneumonia (PcP) following therapy with methotrexate and prednisone. Although bactrim treatment was initiated and PcP was not detected by a control bronchoalveolar lavage, the patient died. The precise cause of death remains unknown. As this case illustrates, PcP must be considered as a differential diagnosis in immunocompromised patients with rheumatic disease. The typical course, diagnosis, prophylaxis and treatment of PcP in this patient group are discussed. | |
16365685 | Disease activity and functional changes of RA patients receiving different DMARDs in clini | 2006 Sep | The aim of this study was to compare the effectiveness of different disease-modifying anti-rheumatic drugs (DMARDs) in improving disease activity and functional status in patients with rheumatoid arthritis (RA). One hundred and fifty-two Thai RA patients treated with at least one DMARD were enrolled in this 1-year cohort. Demographic characteristics, baseline and end-of-study data on disease activity and Health Assessment Questionnaire (HAQ) Disability Index of the subjects were compared among different DMARD options. Predictors of HAQ score were investigated using regression analysis. The results showed that the studied patients had established RA with mild to moderate activity. More than 85% were prescribed methotrexate (MTX) as single or combined DMARDs. At 1 year, improvement in most activity measures was experienced. However, all patients had functional declines. Patients taking antimalarial agents had the maximal rate of functional deterioration. Patients taking MTX-based DMARDs had significantly lower rate of functional decline than patients taking DMARDs without MTX (p=0.018). Only patients receiving MTX-based DMARDs had clinically meaningful improvement in HAQ score. The predictors of HAQ score at 1 year included baseline HAQ score and patient global assessment at end of study. In conclusion, although DMARD treatment was shown to improve disease activity in RA patients, functional deterioration was evident in our cohort. Thus, measures of functional status are more appropriate than measures of disease activity to evaluate treatment effects of DMARDs in established RA in clinical practice. MTX-based DMARDs should be prescribed where possible in RA patients with persisting activity due to their ability to delay functional deterioration. | |
17350542 | Early rheumatoid arthritis: strategies for prevention and management. | 2007 Feb | The treatment of rheumatoid arthritis (RA) has changed considerably in the past few years since new tools and new concepts have been developed and validated highlighting the need for guidelines focused on early RA. The treatment goal should now be to achieve clinical remission, in order to prevent structural damage and long-term disability. A very early use of effective disease-modifying anti-rheumatic drugs (DMARDs) is a key point in patients at risk of developing persistent and erosive arthritis. Intensive treatment such as combination DMARDs plus steroids or biological therapies can induce a high rate of remission, control of radiological progression and provide better outcome than DMARD monotherapy in early RA and should be considered in at risk patients. Regarding the risk:benefit ratio and the cost-effectiveness of these strategies, a reasonable course of action in early RA should be initial DMARD monotherapy such as methotrexate. However, a close monitoring of disease activity and radiographic progression is mandatory in order to change DMARD therapy and strategy if necessary. Systemic glucocorticoids are effective in the short-term relief of pain and swelling and should be considered, but mainly as a temporary therapy part of the DMARD strategy. Information and education for patients, as well as some non-pharmacological interventions, can be proposed as treatment adjuncts. Finally, the reduction or stopping of smoking, which could prevent the development and progression of early RA, is the only prevention tool currently available. | |
17083766 | Remission as the treatment goal--the FIN-RACo trial. | 2006 Nov | The Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial is the first rheumatoid arthritis (RA) clinical trial in which remission served as the primary outcome measure. This chapter reviews the philosophical background, study design, and results of the FIN-RACo trial. The study showed that a third of patients with active early RA may achieve remission with a combination of methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), and prednisolone. | |
18985308 | [Rheumatoid arthritis today]. | 2008 Dec | Advances in the therapy of rheumatoid arthritis with disease modifying antirheumatic drugs (DMARD) such as methotrexate and biological response modifiers in particular, have turned a chronic progressive disease with significant invalidity and mortality into one that can be well controlled. To prevent irreversible damage, early diagnosis is essential. DMARD therapy needs to be instituted within three months after symptom onset - a clinical and organisational challenge. Long term DMARD therapy is monitored using standardized scores and modified whenever not sufficiently successful. Analgesia, physiotherapy and occupational therapy as well as orthopaedic surgery play important roles in the management of rheumatoid arthritis. Consequent multimodal therapy can decisively influence the course of the disease and prevent or at least minimize damage. | |
16761484 | Intestinal necrosis in a patient with rheumatoid arthritis receiving anti-TNF treatment. | 2006 Mar | Vasculitis leading to intestinal necrosis is a rare complication of rheumatoid arthritis. The introduction of anti-TNF treatment for methotrexate-resistant cases improved disease-control substantially in these often more aggresive forms of rheumatoid arthritis. As far as we know only two cases of severe vasculitis following anti-TNF treatment have been reported. We describe a 45-year old female patient with severe rheumatoid arthritis, who presented with an epileptic insult, renal failure and a quickly deteriorating general condition due to intestinal vasculitis, while she had been receiving anti-TNF treatment for 6 months. | |
17286537 | Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in | 2007 Feb | The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. The glutamates are released from MTX by activity of the enzyme gamma-glutamyl-hydrolase (GGH), thereby allowing the efflux of MTX. GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain MTX-polyglutamate. However, single nucleotide polymorphisms (SNPs) in FPGS and GGH genes have not yet been explored for association with MTX efficacy or toxicity. We selected for SNPs with frequencies higher than 10% or, in case of FPGS 114G>A, causing an amino acid change with no known frequencies. In this study, frequencies of two SNPs in FPGS (1994A>G and 114G>A, rs10106 and rs10760502, respectively) and GGH genes (452C>T and 16T>C, rs11545078 and rs1800909, respectively), were determined using a newly developed method in rheumatoid arthritis patients (n = 352) and in a group of healthy controls (n = 360). Next, the SNPs were associated with response to MTX in rheumatoid arthritis patients treated with MTX monotherapy. In rheumatoid arthritis patients, allele frequencies of FPGS 1994A>G were 0.534 (A) and 0.466 (G), and for FPGS 114G>A 0.714 (G) and 0.286 (A). Allele frequencies of GGH 16T>C were 0.737 (T) and 0.263 (C) and for GGH 452C>T 0.912 (C) and 0.088 (T). No significant differences in allele frequencies between rheumatoid arthritis patients and healthy controls were found. In addition, the SNPs were not associated with good clinical response to MTX. Only patients with the GGH 16C-allele and one or no copies of the GGH 452C-16T haplotype were associated with good clinical improvement at 3 months upon treatment with MTX. No associations with efficacy at 6 months and MTX-induced toxicity were found. Therefore we conclude that despite the positive association of the GGH 16C-allele and one or no copies of the GGH 452C-16T haplotype with good clinical improvement at 3 months upon treatment with MTX, the tested SNPs in GGH and FPGS genes are suggested not to be clinically important for MTX treatment outcome. |