Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 9714355 | Injection of the rheumatoid knee: does intra-articular methotrexate or rifampicin add to t | 1998 Jul | OBJECTIVE: Does the addition of 600 mg rifampicin or 50 mg methotrexate improve pain relief after injection of the rheumatoid knee with 20 mg triamcinolone hexacetonide (TH)? METHODS: Eighty-two patients on stable therapy were allocated at random to receive intra-articular TH alone, TH and methotrexate (TH+M) or TH and rifampicin (TH+R). Pain was recorded by a weekly chart and analysed using the area under the curve (AUC), periods of total pain relief and duration of effect. Examinations and microwave thermography were performed by an independent meteorologist at baseline, 3 and 6 months. RESULTS: Using the AUC, pain was significantly better in the TH+R group compared with TH alone (P=0.039, Mann Whitney U). The median duration of improved pain scores was 13.5 weeks with TH alone, 10 with TH+M and 19 with TH+R. Examination and microwave thermography revealed improvements compared with baseline, but there were no significant differences between the groups. Eleven of 28 patients treated with TH + R developed a flare of post-injection pain. CONCLUSIONS: Whilst the addition of rifampicin improved pain relief, the occurrence of pain after injection remains a problem. Measures to minimize this are needed when TH+R is used. | |
| 10660143 | Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with a | 1999 Dec | The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA patients who improved during therapy and 8 healthy controls: 0.8+/-0.12% (mean+/-SEM) versus 0.3+/-0.06% (p<0.002) and 0.3+/-0.06% (p<0.005), respectively. Increased levels of CD11b+CD45R0+ cells were observed in patients with active RA compared to those with improved RA and controls: 12.6+/-3.9% versus 4.8+/-2.7% (p<0.002) and 6.1+/-1.2% (p<0.003), respectively. Disease activity, determined by C-reactive protein, correlated with the numbers of CD11b+CD45R0+ cells: r=0.62 (p<0.001). Seven patients were followed during induction of remission with methotrexate and glucocorticoids. The numbers of CD11b+CD4+ and CD11b+CD45R0+ cells fell significantly after clinical improvement. The levels of CD11b+CD14+ cells (monocytes) did not differ between the groups. The number of CD11b+CD15+ cells (neutrophils) was elevated in patients with RA irrespective of disease activity. The levels of CD54+ cells were not different between the RA and control groups. We conclude that the increased numbers of CD11b+ memory T cells may arise from exposure to stimuli outside the synovial compartment. | |
| 10090188 | Validity of area-under-the-curve analysis to summarize effect in rheumatoid arthritis clin | 1999 Mar | There is a continuing interest in increasing the statistical efficiency of the analysis of clinically meaningful endpoints in rheumatology. One issue that is attracting increasing attention is whether the conventional practice of only reporting the outcome at the end of the study (EOS) might be replaced or complemented by a longitudinal summary that better reflects the clinical course of the disease. The area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study. We evaluated the utility of AUC as a summary measure for the analysis and reporting of two RA trials: (i) methotrexate combined with cyclosporine versus methotrexate and placebo in partial methotrexate responders in relatively late disease, and (ii) prednisone plus methotrexate plus sulfasalazine versus sulfasalazine alone in relatively early disease. We replicated the published results of each trial first using the conventional EOS and then AUC summaries. For each patient, the changes from baseline over time were transformed into a summary measure by calculating AUC using the trapezium rule and then standardizing it by the study duration. Using an approach similar to the index of responsiveness to change, we scaled treatment differences derived from EOS and AUC summary measures by their standard deviation of the control group. This signal-versus-noise ratio captures the treatment discrimination ability of each summary measure. Compared to EOS and within each treatment group, the AUC summary reported smaller effects (i.e., change from baseline) with reduced errors in the estimates. AUC measures preserved discriminant validity in treatment comparisons and reported smaller but more precise treatment effect estimates. In the COBRA trial with rapidly-acting medications, AUC seemed to be more sensitive than EOS to detect treatment difference. With slow acting medications and in relatively late disease patients as in the cyclosporine trial, EOS was more sensitive to detect treatment difference than was AUC. In this setting, AUC, however, still seemed to be more sensitive than EOS for the two responsive-to-change endpoints: tender joint counts and pain by visual analog scale. AUC integrates repeated assessments during the trial duration into summary measures. Compared to EOS, the report of RA trial results using AUC summary provides smaller estimates of treatment effects but with better precision. AUC summary is likely to preserve treatment group discrimination taking into account the appropriate onset and offset of the drug action. Trial reports using AUC summary have smaller effect sizes. For trials with long acting medications and short duration similar to the cyclosporine trial, AUC still preserves treatment discrimination but may not be as sensitive as EOS. The calculations of AUC require some additional work in the analysis of each endpoint. | |
| 11060789 | Sjögren's syndrome: current therapies remain inadequate for a common disease. | 2000 Sep | Sjögren's syndrome (SS) is a systematic autoimmune disease characterised by dysfunction of the lacrimal and salivary glands. This dryness leads to the symptoms of dry eyes and keratoconjunctivitis sicca, which is painful and may predispose patients to ocular infections. Also, SS patients develop dry mouth, which is uncomfortable and associated with progressive dental disease. SS is divided into secondary SS (where the dryness symptoms are associated with another well defined autoimmune disorder such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma) and primary SS (where the patients do not fulfil criteria for another well defined associated autoimmune disease). Primary SS has extra glandular organ involvement including lung (interstitial pneumonitis), renal (interstitial nephritis), peripheral and central nervous system manifestations, vasculitis of skin and other organs and increased frequency of lymphoma. This review will concentrate on primary SS. Therapies are divided into agents for topical replacement of deficient secretions (artificial tears, artificial salivas), stimulation of muscarinic M3 receptors (pilocarpine, cevimeline) to increase aqueous secretions, reduction of topical inflammation (topical cyclosporin or corticosteroids for the eye and fluorides or antibacterial varnishes for the mouth) and modification of the immune response in a manner similar to treatment of systemic lupus (antimalarial drugs, methotrexate, cyclophosphamide and perhaps newer agents such as leflunomide or TNF inhibitors). | |
| 11499826 | Cutaneous lymphoma associated with Epstein-Barr virus infection in 2 patients treated with | 2001 Aug | Whether patients with rheumatoid arthritis (RA) have an increased risk of developing non-Hodgkin lymphoma is controversial, and opinions differ on the possible role of methotrexate in the occurrence of lymphomas in patients with RA. We report 1 T-cell lymphoma and 1 B-cell lymphoma restricted to the skin associated with Epstein-Barr virus infection that healed completely and spontaneously after discontinuation of methotrexate in a man with RA and a woman with dermatomyositis. Cutaneous infiltrating cells were infected by a replicative form of Epstein-Barr virus. After discontinuation of methotrexate, the cutaneous lesions disappeared completely in 15 days without recurrence. Discontinuation of methotrexate is necessary in patients with RA or dermatomyositis who have a lymphoproliferative disorder, and a follow-up period of several weeks should be observed before specific therapy is initiated. | |
| 11892935 | Etanercept. Immunex. | 2001 Dec | Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of rheumatoid arthritis (RA). It has also been developed for various TNF-mediated conditions such as congestive heart failure, endometriosis and multiple sclerosis. Etanercept has been launched as a second-line agent in the US for the treatment of moderate-to-severe RA and can be used in conjunction with methotrexate in patients unresponsive to methotrexate alone. It is also available in the EU. In 2000, it was in phase III trials for psoriatic arthritis and an NDA filing for this indication was expected for the first half of 2001. In July 2001, the sBLA was filed, and in September 2001, the FDA granted the sBLA Priority Review status. As of January 2001, etanercept was in phase III trials for congestive heart failure, with sNDA filing expected in 2002; however, by March 2001, these had been halted, as it did not appear that statistical significance would be reached for the efficacy endpoints. Further data analysis was being undertaken at this time, before a final decision was taken. In April 2001, Merrill Lynch reported that development for this indication was to be halted. Sales for the drugs first full quarter on the market in 1999 were US $59.7 million. By November 1999 the drug had made sales of US $500 million; Immunex expected the drug to generate over US $2 billion in annual sales by 2004. In September 2000, Merrill Lynch reported that if sales of the drug continued at the present rate then it is likely that demand would temporarily outstrip supply in 2001. Resolution of the supply issue was expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believed that the drug has the potential to exceed US $5 billion in sales in the US. In April 2001, Merrill Lynch predicted that etanercept prescribed for RA would generate sales of US $71 in 2002 rising to US $600 million in 2005. In October 2001, Morgani Stanley reported that Enbrel continues to be the primary source of revenue of Immunex (US $198.1 million). It was also reported that if launched for CHF, an estimated peak year revenue was likely to be US $500 million. The company maintains a website containing additional information about etanercept at http://www.enbrelinfo.com. | |
| 11246658 | Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: possible mechanism of M | 2001 Feb | OBJECTIVE: To clarify the mechanism of impaired bone formation during low dose methotrexate (MTX) therapy. METHODS: The in vitro effects of MTX on the function and differentiation of osteoblastic cells were investigated using (1) a mouse osteogenic cell line (MC3T3-E1) with the capacity to differentiate into osteoblastic or osteocytes, (2) a human osteoblastic osteosarcoma cell line (SaOS-2) with a mature osteoblastic phenotype, and (3) mouse bone marrow stromal cells containing osteoblast precursors. Osteoblast function was assessed by measuring the cellular activity of alkaline phosphatase (ALP) and the mineralization capacity of cultures. RESULTS: MTX suppressed ALP activity dose-dependently in growing MC3T3-E1 cells, but proliferation of these cells was only inhibited by a high concentration of MTX. In contrast, inhibition of ALP activity in MC3T3-E1 cells of mature osteoblastic phenotype was only observed with 10(-8) M and 10(-7) M MTX, and proliferation was not influenced. ALP activity and the proliferation of SaOS-2 cells were not inhibited by MTX, even when growing cells were treated. However, both ALP activity and formation of calcified nodules in bone marrow stromal cell cultures were significantly suppressed by MTX at concentrations between l0(-10) and 10(-7) M. CONCLUSION: These results suggest that MTX suppresses bone formation by inhibiting the differentiation of early osteoblastic cells. | |
| 17039088 | Worsening of arthritis with antiretroviral therapy: the coexistence of rheumatoid arthriti | 2001 Feb | The observation of remission occurring in several rheumatoid arthritis (RA) patients who subsequently became infected with human immunodeficiency virus (HIV) suggested that these diseases are mutually exclusive. Subsequent case reports of progression of destructive rheumatoid arthritis, even with depleted CD4 cell counts, seemed to imply that active RA may be independent of CD4 lymphocyte number and function. We report an HIV-infected individual who developed rheumatoid arthritis, which rapidly worsened with the initiation of antiretroviral therapy. The worsening disease course correlated with the increase in CD4 cell count and with the decrease in HIV viral load, perhaps suggesting a central role for the CD4 cells in the pathogenesis of rheumatoid arthritis in this particular patient. Among the therapeutic options to consider in such a patient, indomethacin and hydroxychloroquine may offer additional benefit of inhibiting viral replication. The cautious use of methotrexate with several limitations is possible, although sulfasalazine (to which our patient responded) may be a safer option. | |
| 10893476 | Effect of methotrexate on the temporomandibular joint and facial morphology in juvenile rh | 2000 Jul | Juvenile rheumatoid arthritis is a disease characterized by chronic inflammation in one or more joints; it affects children and adolescents up to 18 years of age. This disease may cause significant skeletal joint destruction, and the temporomandibular joint, like other joints, may become severely affected resulting in aberrant mandibular growth, abnormal dentofacial development, and/or altered orofacial muscle function. Methotrexate is the most common remittive agent used in juvenile rheumatoid arthritis to modify the course of inflammatory destruction of peripheral joints. The purpose of this study was: (1) to evaluate the effect of methotrexate therapy on the prevalence of temporomandibular joint lesions and aberration in craniofacial development in children afflicted with juvenile rheumatoid arthritis; (2) to further examine the relationship between the temporomandibular joint/cephalometric findings and rheumatologic data (ie, age at onset, duration of disease); and (3) to evaluate further pauciarticular- and polyarticular-onset disease in juvenile rheumatoid arthritis and the prevalence of temporomandibular joint lesions and facial dysmorphology. The following information was obtained from 45 patients with juvenile rheumatoid arthritis: (1) routine rheumatologic clinical examination data; (2) anamnestic temporomandibular joint evaluation data; (3) clinical temporomandibular joint examination data; (4) lateral cephalometric measurement data; (5) posteroanterior cephalometric measurement data; and (6) individually corrected axial tomographic data. The results demonstrated the following: (1) radiographic evidence of condylar degeneration was apparent in 63% of all patients with juvenile rheumatoid arthritis with pauciarticular patients showing less temporomandibular involvement than polyarticular patients; (2) polyarticular juvenile rheumatoid arthritis patients receiving methotrexate showed less severe temporomandibular joint involvement than the polyarticular patients not receiving methotrexate; (3) the craniofacial structure was affected to a greater extent in the polyarticular form of the disease; (4) the craniomandibular index scores were significantly greater in the polyarticular group; (5) vertical height asymmetry and chin deviation were noted in more than 50% of the patients; and (6) there was a correlation between the severity of condylar lesions and cephalometric findings (ie, mandibular retroposition, posterior rotation, smaller ramus and mandibular dimensions) and the onset and duration of the disease. In conclusion, under the conditions of this study, methotrexate therapy was effective in minimizing temporomandibular joint destruction and craniofacial dysmorphology in juvenile rheumatoid arthritis patients with the polyarticular form of the disease. | |
| 10503657 | Juvenile rheumatoid arthritis. | 1999 Sep | The heterogeneous nature of juvenile rheumatoid arthritis is further defined in publications from the past year. Decreased IL-10 production, an anti-inflammatory cytokine, and soluble IL-6 receptor are associated with systemic juvenile rheumatoid arthritis (JRA). IL-4 may have an anti-inflammatory role in the pathogenesis of pauciarticular JRA and may protect, along with IL-10, against the development of joint erosions. Active JRA is associated with lower levels of platelet activating factor acetylhydrolase, which may contribute to the loss of anti-inflammatory activity and increased risk of atherogenesis. The phase 3 clinical trial of etanercept confirmed its efficacy and safety in JRA. Intra-articular steroids are safe and effective in the treatment of JRA. Methotrexate does have disease-modifying effects. The risk of hepatotoxicity with methotrexate use increases with serial transaminase abnormalities and with obesity. Osteoclasts are responsible for joint erosions. Cyclosporine A, mycophenolate mofetil, and methotrexate are effective in the treatment of refractory uveitis. During the past year a number of scientific publications have contributed significantly to our understanding and treatment of juvenile rheumatoid arthritis. | |
| 9602213 | Methotrexate-induced hypersensitivity pneumonitis in a child with juvenile rheumatoid arth | 1998 May | Low-dose methotrexate, widely used for juvenile rheumatoid arthritis, has been reported to cause pneumonitis in adults. We report on methotrexate-induced hypersensitivity pneumonitis in a child with juvenile rheumatoid arthritis. Physicians should be aware of this rare complication. | |
| 10370653 | Gastroduodenal lesions in children with juvenile rheumatoid arthritis. | 1999 Mar | BACKGROUND/AIMS: There are few studies about gastrointestinal abnormalities in patients with juvenile rheumatoid arthritis-probably due to the fact that this association is not frequently recognized. The aim of our study was to observe the prevalence of endoscopic gastroduodenal lesions in these patients. METHODOLOGY: Fourteen patients with juvenile rheumatoid arthritis, all of them using non-steroidal anti-inflammatory drugs associated or not with methotrexate, were assessed clinically and by endoscopy. Gastric antrum biopsy and Helicobacter pylori search were also performed. RESULTS: The mean age of the patients was 10.6 years (7 boys). Abdominal pain was observed in 27% of them. Macroscopic endoscopic lesions were found in 43% and infection by Helicobacter pylori in 57%. The correlation between anemia and endoscopic abnormalities was statistically significant (p < 0.05). CONCLUSIONS: Our data show that patients with juvenile rheumatoid arthritis have considerable susceptibility to gastroduodenal lesions, especially if they are using any drug association and present anemia. | |
| 19078194 | Prodromal urticaria with seronegative rheumatoid arthritis. | 1997 Aug | This case report describes an association of chronic diurnal urticaria with the onset of seronegative arthritis in a 38-year-old woman after her first pregnancy. Remission of the urticaria and rheumatoid arthritis occurred with methotrexate therapy. The variety of urticarial lesions that can be seen with arthritis are noted. | |
| 9055198 | Low-dose pulse methotrexate inhibits articular destruction of adjuvant arthritis in rats. | 1997 Feb | The purpose of this study was to determine whether low-dose methotrexate pulse therapy, which had recently become important in the treatment of rheumatoid arthritis, was effective for controlling the progression of articular destruction in rats with adjuvant arthritis. Intraperitoneal methotrexate at a dose of 0.05 or 0.1 mg kg-1 twice weekly inhibited inflammation in rats with adjuvant arthritis, as shown by reduction of the hind-paw volume. Methotrexate also inhibited articular destruction, as shown by X-ray findings. Although the mechanisms by which low-dose pulse methotrexate acts on rat adjuvant arthritis are still unclear, our results imply that it might effectively slow the progression of articular destruction in rheumatoid arthritis in man. In addition, assessment of articular destruction in this animal model might be useful when evaluating new treatments for rheumatoid arthritis. | |
| 11411961 | Keratonconjunctivitis sicca is not uncommon in children with juvenile rheumatoid arthritis | 2001 May | Keratoconjunctivitis sicca (KCS), characterised by aqueous tear deficiency, is the most common ocular complication in adult rheumatoid arthritis (RA). In juvenile rheumatoid arthritis (JRA), however, it remains under-reported. For this prospective study, 50 children with JRA were examined clinically and underwent tests for KCS (Schirmer's I and rose bengal tests, fluorescein staining, and tear film breakup time). Six children (12%) with two or more abnormal tests were diagnosed as having definite KCS, while one child with only one abnormal test was labelled with probable KCS. Five of the six (83.3%) with definite KCS were males, and three (50%) had a pauciarticular form of the disease. Two children (33.3%) with definite KCS had no ocular symptoms, five were receiving only nonsteroidal anti-inflammatory drugs, and one was additionally on methotrexate. Keratoconjunctivitis sicca appears to be a common ocular complication and all children with JRA should be screened for it with a comprehensive battery of tests. | |
| 18020613 | Cyclosporin in rheumatoid arthritis: monitoring for adverse effects and clinically signifi | 1998 Dec | While cyclosporin has an established role in the treatment of rheumatoid arthritis there is concern about adverse effects, mainly related to renal function. With new interest being generated in cyclosporin combination therapy, and the availability of a new form of cyclosporin (cyclosporin microemulsion), focus on adverse effects and drug interactions of this compound remains important. Over the years, rheumatologists have been aware of these adverse effects and consensus meetings have resulted in guidelines for the use of cyclosporin. If these guidelines are followed, structural renal damage can be minimal. Cyclosporin should be started at a low dose and titrated against the highest acceptable increase in serum creatinine, that is, a 30% increase over the pretreatment value. At present, there is no evidence that cyclosporin in combination with other antirheumatics leads to increased toxicity. With regard to long term unwanted effects, neither the pattern nor the risk of malignancies associated with the use of cyclosporin seems to differ from other antirheumatics. The place of cyclosporin in the treatment of rheumatoid arthritis seems to be established. The most promising results will come from early rheumatoid arthritis combination studies involving cyclosporin with other antirheumatics, especially methotrexate. | |
| 9709718 | Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. | 1998 Aug | We used low-dose methotrexate to treat seven children with juvenile rheumatoid arthritis-associated uveitis complicated by cataract and glaucoma or resistant to topical corticosteroid. The use of methotrexate decreased the severity of uveitis in six of seven patients and allowed for the discontinuation or reduction of corticosteroid drops. | |
| 9746863 | Juvenile rheumatoid arthritis and spondyloarthropathies. | 1998 Sep | This paper reviews the current literature on the clinical aspects of juvenile rheumatoid arthritis (JRA) and the juvenile spondyloarthropathies. The classification of the juvenile arthritides remains controversial. A sibling pair registry established a role for genetic influences on the onset and course types of JRA. Even in the absence of steroid treatment, children with JRA demonstrated decreased bone mineral density and an impairment of linear growth. Magnetic resonance imaging was found to be helpful in detecting subtalar or sacroiliac involvement. Studies were published on the use of azathioprine, cyclosporine, and cyclopyhosphamide in the treatment of severe JRA. The lack of severe liver toxicity was shown in patients having received high total doses of methotrexate. An international agreement was reached on defining improvement in JRA. Several studies found an improved long-term outcome in patients with JRA or the juvenile spondyloarthropathies. | |
| 9880448 | The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy f | 1999 Jan | OBJECTIVE: To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). STUDY DESIGN: We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children's Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. RESULTS: Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities (P <.001) and body mass index (P =.05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. CONCLUSIONS: Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA. | |
| 18020507 | Methotrexate in rheumatoid arthritis: folate supplementation should always be given. | 1997 Sep | Methotrexate is now the disease-modifying antirheumatic drug prescribed most frequently for the treatment of rheumatoid arthritis. Methotrexate is an antifolate that inhibits methylation reactions and reactions of amino acid, purine and pyrimidine metabolism. Toxic manifestations of methotrexate administration for rheumatoid arthritis (at relatively low doses compared with those used in cancer chemotherapy) include cytopenias, gastrointestinal intolerance, liver disease, pulmonary injury, central nervous system dysfunction, skin rashes and nodulosis. Delayed wound healing and increased risk for infections with opportunistic organisms also occur. Some of these toxic manifestations respond to supplementation with folates [folic acid or folinic acid (calcium folinate)]. The folate status of patients has been shown to be impaired after prolonged treatment with methotrexate, and poor baseline folate status is an independent risk factor for subsequent toxicity. Numerous studies have now documented that folic acid, even in high doses, and moderate doses of folinic acid are beneficial in preventing methotrexate toxicity without affecting efficacy. In this article we present guidelines and rationale for monitoring methotrexate therapy, and guidelines for folate supplementation during methotrexate therapy for rheumatoid arthritis. It is our recommendation that folic acid should be empirically supplemented in all patients at the initiation of methotrexate therapy. This regimen is associated with a high benefit : risk ratio and is likely to be cost effective. |