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ID PMID Title PublicationDate abstract
15757966 Down-regulation of activating Fcgamma receptors on monocytes of patients with rheumatoid a 2005 Jun OBJECTIVE: To determine the effect of methotrexate (MTX) on expression levels of activating receptors for IgG (FcgammaRs) on monocytes of rheumatoid arthritis (RA) patients in relation to changes in disease activity. METHODS: The effect of MTX on FcgammaRs on monocytes of RA patients was evaluated ex vivo as well as in vitro. Recently diagnosed, disease-modifying antirheumatic drug (DMARD)-naive RA patients were treated with low-dose MTX. At baseline and 16 weeks after the start of MTX treatment, changes in FcgammaR expression levels on peripheral blood monocytes were evaluated by fluorescence-activated cell sorting analysis and were correlated to changes in disease parameters. To study the direct effects of MTX on monocytes, these cells were isolated from peripheral blood monocytes of healthy controls and cultured with MTX. Other monocyte surface molecules (CD40, CD80, CD86, MHC class II) were also determined to test the specificity of the effect on FcgammaR expression levels. RESULTS: Eleven out of 15 patients improved clinically (mean disease activity score before 6.2 +/- 0.8 vs 4.3 +/- 1.7 after). Sixteen weeks after the start of MTX therapy, the expression levels of FcgammaRI and IIa on monocytes were significantly decreased, whereas the decreases in FcgammaRIIIa expression levels on monocytes were less marked. The percentage decrease in FcgammaRI expression correlated with the percentage decrease in CRP and well-being. In vitro MTX selectively decreased FcgammaRI and FcgammaRIIa expression levels of isolated monocytes, in contrast to other surface molecules. CONCLUSION: The disease-modifying effect of MTX in the treatment of RA is accompanied by down-regulation of activating FcgammaRI and IIa on monocytes, which could be a direct effect of MTX on monocytes. This down-regulation represents a new mode of action of MTX which should be considered in RA patients, especially during conditions that could give rise to monocyte activation by IgG-containing immune complexes, e.g. during antibody-based therapy of RA.
16208641 Current use of glucocorticoids in patients with rheumatoid arthritis in Germany. 2005 Oct 15 OBJECTIVE: To describe the current use of glucocorticoids in German patients with rheumatoid arthritis (RA). METHODS: We analyzed clinical and patient-derived data from 10,068 outpatients with RA from the national database of the German Collaborative Arthritis Centres for the year 2001 collected by more than 80 rheumatologists in hospitals and private practices. RESULTS: Systemic glucocorticoid therapy was prescribed for 60% of all patients with RA in rheumatologic care. The proportion of patients receiving systemic glucocorticoids in addition to disease-modifying antirheumatic drug (DMARD) therapy ranged from 53% to 81% of the patients for the various DMARDs. Glucocorticoid therapy was administered more often in combination with tumor necrosis factor inhibitors (81%), cyclosporin A (80%), or leflunomide (77%) than with more traditional DMARDs such as methotrexate (63%) or sulfasalazine (55%). Regarding the prevention and treatment of osteoporosis, 63% of patients taking systemic glucocorticoids were also receiving some type of osteoporosis therapy, as opposed to only 26% of those not taking glucocorticoids. CONCLUSION: Glucocorticoids play a pivotal role in the management of RA. This is reflected in the extensive use of low-dose glucocorticoids by German rheumatologists. Even if highly effective DMARDs are prescribed, they are accompanied by glucocorticoids, at least in the initial phase. High-dose glucocorticoids are prescribed for only a small proportion of the patients. There is increasing awareness of the risk of osteoporosis in long-term glucocorticoid treatment, demonstrated by the fact that osteoporosis medication is prescribed for a large proportion of patients taking glucocorticoids.
16762151 Suppression of circulating interleukin-6 concentrations is associated with decreased endot 2006 Mar BACKGROUND: Circulating interleukin (IL)-6 concentrations are associated with endothelial activation in rheumatoid arthritis (RA). OBJECTIVE: To assess endothelial activation before and after suppression of cytokine production in RA. METHODS: Twenty-one patients (mean (SD) age 59 (9) years; disease duration 6 (4) years) were treated with intraarticular methylprednisolone acetate (417 (152) mg) together with disease modifying agent (DMARD) initiation (n = 10) or intensification (n = 11) employing methotrexate (n = 11), leflunomide (n = 8), minocyclin (n = 6) and sulphasalazine (n = 1). Disease activity, circulating cytokines (IL-1, tumor necrosis factor alpha (TNF-alpha) and IL-6) and biomarkers of endothelial activation (circulating vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1)) were evaluated before and 2 weeks after treatment. RESULTS: The intervention resulted in reductions in 8 disease activity markers (p < or = 0.002). Serum IL-6 concentrations decreased from 17 (2.9) to 4.9 (4.6) pg/ml (p = 0.0008). Serum IL-1 and TNF-alpha levels did not change (p > or = 0.4). Serum VCAM-1 concentrations decreased from 912 (402) to 752 (252) (p = 0.003), ICAM-1 from 398 (205) to 323 (179) (p = 0.04) and ELAM-1 from 68 (28) to 53 (25) (p = 0.02) pg/ml, respectively. Baseline rheumatoid factor titers were associated with reductions in VCAM-1 (r(s) = 0.481, p = 0.03). In multivariable regression models, decreases in circulating interleukin-6 concentrations were associated with reductions in VCAM-1 (p < 0.0001), ICAM-1 (p = 0.005) and ELAM-1 (p = 0.02) independent of changes in disease activity, weight and blood pressure. CONCLUSION: Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.
16892137 [Therapeutic effect and impact on cytokine production by methotrexate in rheumatoid arthri 2006 Aug 18 OBJECTIVE: To examine the clinical benefit and impact on cytokine production by methotrexate in rheumatoid arthritis. METHODS: Thirty patients with RA were treated with oral methotrexate (mean, 15 mg per week) as monotherapy for 24 weeks. Clinical assessment using the American College of Rheumatology (ACR) criteria for improvement was performed at baseline and at the end of 2, 4, 8, 12 and 24 weeks. The pro-inflammation cytokine TNF-alpha, INF-gamma,IL-1beta, IL-6 and anti-inflammation cytokine IL-10 were measured in RA sera at baseline and after 24 weeks of therapy. RESULTS: There was remarkable improvement in disease activity following the MTX treatment. At the end of 24 weeks, the percent age of ACR20 was 70% (21/30), ACR50 30% (9/30) and ACR70 10% (3/30). The levels of IL-6 (46.83+/-35.81 vs. 20.92+/-17.98, P=0.001), TNF-alpha (162.52+/-107.63 vs. 18.32+/-14.36, P=0.026) and INF-gamma (67.79+/-43.76 vs. 35.78+/-27.51, P=0.004) were significantly higher than those of the health control at baseline, respectively. The levels of TNF-alpha (123.36+/-89.61,P=0.018), INF-gamma (41.53+/-13.49, P=0.015), IL-1beta (7.47+/-7.33, P=0.026), IL-6 (26.01+/-25.64, P=0.025) were significantly decreased after treatment with methotrexate. In contrast, IL-10 was remarkably increased (71.76+/-41.01, P=0.02). CONCLUSION: Methotrexate is effective in patients with rheumatoid arthritis. It can suppress the symptoms and joint damage. In addition, methotrexate treatment decreases the levels of pro-inflammatory cytokine, and increases the level of anti-inflammatory cytokine.
16906378 Development of interstitial pneumonia in a rheumatoid arthritis patient treated with infli 2006 Infliximab, an anti-tumor necrosis factor (TNF)-alpha antibody, was introduced to a 66-year-old woman with methotrexate (MTX)-resistant rheumatoid arthritis (RA). Although the TNF-blocking therapy was successful, she developed noninfectious interstitial pneumonia (IP) after a second infusion of infliximab. In most cases reported previously, infliximab-associated noninfectious IP occurred after a second or third infusion of infliximab, and this type of IP was more fatal in comparison with cases associated with MTX treatment alone. Keeping a sharp lookout on IP development during this period is crucial to the success of infliximab treatment. After MTX discontinuation and steroid pulse therapy, our patient made a dramatic recovery from IP.
16435580 Artemether: a new therapeutic strategy in experimental rheumatoid arthritis. 2005 The current research was designed to determine the effect of artemether in treatment of experimental rheumatoid arthritis. Collagen-induced arthritis was induced in Lewis rats. The intramusculary administration of artemether (ART) and intraperitoneally injection of methotrexate (MTX) were started on day 25 postimmunization and continued until final assessment on day 35. During this period, clinical examination was taken intermittently. The anticollagen type II antibody (CII Ab) and nitric oxide synthesis were measured. The paws and kness were then removed for histopathology and radiography assay. The biocompatibility of ART and MTX were assessed using fibrosarcoma cell line. Data showed that i.m. injection of ART to arthritic rats induced a significant reduction in paw edema. This beneficial effect was associated with a significant decrease in anti-CII antibody response compared with untreated rats. Histopathological assessment showed a reduced inflammatory cell infiltrate in joints of treated rats; tissue edema, and bone erosion in the paws were markedly reduced following ART therapy. Furthermore, our radiography results paralleled our histological findings. Cytotoxicity analysis of ART showed greater tolerability compared with MTX. Treatment with ART significantly diminished NO formation in treated rats compared with nontreated controls. Our data shed light on the therapeutic efficacy of artemether in experimental rheumatoid arthritis compared with a choice drug (methotrexate), and it may be offered as a second-line drug in treatment of rheumatoid arthritis.
16357696 Drug-induced lupus after treatment with infliximab in rheumatoid arthritis. 2005 Feb We report a case of a 45-year-old man with an 8-month history of rheumatoid arthritis, who was treated with hydroxychloroquine 400 mg per day and 15 mg intramuscular methotrexate per week without reaching a good control of the disease. The patient was successfully treated with 3 mg/kg infliximab for 20 weeks. Before the last infusion, drug-induced lupus (DIL) was diagnosed based on the clinical features of fever > 37.5 degrees C, recurrence of active synovitis, myalgia, erythematosus rash, pericardial and pleural effusion, and of some laboratory findings (antinuclear antibodies 1:160 and anti double-strand DNA positive by DNA recombinant plasmid assay dsDNA). After infliximab discontinuation and the beginning of therapy with methylprednisolone, lupus symptoms resolved within 6 weeks. A new rheumatoid arthritis flare, occurring after 8 weeks, was controlled by methotrexate plus leflunomide. We also review the development of antinuclear and antidouble-strand DNA antibodies and drug-induced lupus in patients treated with anti-TNFalpha agents (infliximab, etanercept, and adalimumab).
17117491 Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 2007 Feb OBJECTIVE: Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. METHODS: We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. RESULTS: Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). CONCLUSION: The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.
16932953 The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with diseas 2006 Nov OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The MDR1 gene product, P-glycoprotein (P-gp), is probably one of the most important and best defined transporters for drug delivery in humans. P-gp transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T MDR1 gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T MDR1 gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs.
16981801 Review of eight pharmacoeconomic studies of the value of biologic DMARDs (adalimumab, etan 2006 Sep BACKGROUND: Treatment options for the management of rheumatoid arthritis (RA) have expanded from the traditional disease-modifying antirheumatic drugs (DMARDs) to include the biologic DMARDs that inhibit tumor necrosis factoralpha (TNF-a). OBJECTIVE: To assess the medical literature for studies of the economic value of biologic DMARDs, specifically the 3 TNF-a inhibitors (adalimumab, etanercept, and infliximab) used for the management of RA, compared with the traditional DMARDs such as sulfasalazine, antimalarials, penicillamine, gold, methotrexate, azathioprine, leflunomide, and cyclophosphamide. METHODS: A comprehensive search of the MEDLINE and HealthSTAR databases was conducted to identify cost-efficacy, cost-effectiveness, or cost-utility studies published in the English language (from 1966 through November 2004). The search terms and/or MeSH (medical subject headings) titles were cost-benefit analysis, rheumatoid arthritis, antirheumatic agents, antineoplastic and immunosuppressive agents. Studies were critically reviewed and quality was assessed using the Quality of Health Economic Studies instrument. Most studies evaluated the use of biologics among RA patients resistant to DMARDs. Studies were assessed with regard to comparators evaluated, measures of efficacy, perspectives, model duration, treatment duration, and discount rate. RESULTS: From 180 titles identified, 155 were excluded for the following reasons: 89 because they did not consider the drugs of interest, 15 because the population was not RA, 19 because of having the wrong drugs and population, 22 because they were review articles, and 10 because they were general articles. Twentyfive abstracts were accepted for further review. Of these, 13 abstracts were subsequently selected for full-text review. One of the authors identified a study not indexed in MEDLINE. Ultimately, 2 cost-effectiveness and 6 cost-utility studies were selected for this critical review. One study over 6 months reported that triple therapy with DMARDs (methotrexate-hydroxychloroquine-sulfasalazine) was cost effective for methotrexate-resistant patients, which is consistent with American College of Rheumatology (ACR) guidelines that support the use of triple therapy prior to biologics. The incremental cost-effectiveness ratio (ICER) was $1,500 per patient to achieve an ACR20 response for this triple therapy compared with no second-line agent. Overall, biologic therapies cost considerably more than traditional DMARDs but produced more quality-adjusted life-years (QALYs). Despite differences in design and assumptions, published economic models consistently reported ICERs <50,000 dollars per QALY gained for biologics compared with traditional DMARDs, although ICERs of >100,000 dollars were reported from sensitivity analyses. CONCLUSIONS: Clinical guidelines currently recommend the use of biologics as step therapy after failure of traditional DMARDs. Reported ICERs comparing biologics with traditional DMARDs are within a range that is comparable with other accepted medical interventions. The worth of the additional expenditure will ultimately be judged by formulary and policy decision makers because no maximum cost has been defined. Models can be used to inform decision makers, but they must be interpreted and applied carefully. More research is also needed to differentiate the relative economic value of the various biologic agents by therapeutic indication.
16049881 [Rheumatoid arthritis]. 2005 Jul 29 The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.
16357751 Selective costimulation modulators: a novel approach for the treatment of rheumatoid arthr 2005 Jun T cells have a central role in the orchestration of the immune pathways that contribute to the inflammation and joint destruction characteristic of rheumatoid arthritis (RA). The requirement for a dual signal for T-cell activation and the construction of a fusion protein that prevents engagement of the costimulatory molecules required for this activation has led to a new approach to RA therapy. This approach is mechanistically distinct from other currently used therapies; it targets events early rather than late in the immune cascade, and it results in immunomodulation rather than complete immunosuppression. The fusion protein abatacept is a selective costimulation modulator that avidly binds to the CD80/CD86 ligands on an antigen-presenting cell, resulting in the inability of these ligands to engage the CD28 receptor on the T cell. Abatacept dose-dependently reduces T-cell proliferation, serum concentrations of acute-phase reactants, and other markers of inflammation, including the production of rheumatoid factor by B cells. Recent studies have provided consistent evidence that treatment with abatacept results in a rapid onset of efficacy that is maintained over the course of treatment in patients with inadequate response to methotrexate and anti-tumor necrosis factor therapies. This efficacy includes patient-centered outcomes and radiographic measurement of disease progression. Abatacept has also demonstrated a very favorable safety profile to date. This article reviews the rationale for this therapeutic approach and highlights some of the recent studies that demonstrate the benefits obtained by using abatacept. This clinical experience indicates that abatacept is a significant addition to the therapeutic armamentarium for the management of patients with RA.
15987483 Decreased levels of soluble receptor for advanced glycation end products in patients with 2005 The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily being expressed as a cell surface molecule and binding a variety of ligands. One of these ligands is high-mobility group box chromosomal protein 1, a potent proinflammatory cytokine, expression of which is increased in synovial tissue and in synovial fluid of rheumatoid arthritis (RA) patients. The interaction of high-mobility group box chromosomal protein 1 with cell-surface RAGE leads to an inflammatory response. In contrast, the presence of soluble RAGE (sRAGE) may abrogate cellular activation since the ligand is bound prior to interaction with the surface receptor. Our aim was to analyse to what extent sRAGE is present in patients with chronic joint inflammation (RA) as compared with patients with non-inflammatory joint disease and with healthy subjects, and to assess whether there is an association between sRAGE levels and disease characteristics. Matching samples of blood and synovial fluid were collected from 62 patients with RA with acute joint effusion. Blood from 45 healthy individuals, synovial fluid samples from 33 patients with non-inflammatory joint diseases and blood from six patients with non-inflammatory joint diseases were used for comparison. sRAGE levels were analysed using an ELISA.RA patients displayed significantly decreased blood levels of sRAGE (871 +/- 66 pg/ml, P < 0.0001) as compared with healthy controls (1290 +/- 78 pg/ml) and with patients with non-inflammatory joint disease (1569 +/- 168 pg/ml). Importantly, sRAGE levels in the synovial fluid of RA patients (379 +/- 36 pg/ml) were lower than in corresponding blood samples and correlated significantly with blood sRAGE. Interestingly, a significantly higher sRAGE level was found in synovial fluid of RA patients treated with methotrexate as compared with patients without disease-modifying anti-rheumatic treatment.We conclude that a decreased level of sRAGE in patients with RA might increase the propensity towards inflammation, whereas treatment with methotrexate counteracts this feature.
16641043 Conversion towards an atherogenic lipid profile in rheumatoid arthritis patients during lo 2006 Mar OBJECTIVES: To analyse the effects of infliximab infusions on serum levels of lipids in patients with rheumatoid arthritis (RA) treated for 2 years. METHODS: Fifty-two patients (41 females and 11 males) with RA undergoing infliximab treatment (3 mg/kg) were consecutively recruited into the study. The mean (+/-SD) age of the patients was 54.6+/-12.5 years and mean disease duration was 14.1+/-8.6 years. Blood was sampled before infusion at baseline, and at 3, 6, 12, 18 and 24 months. Forty-one of the patients were also treated with methotrexate, 13 with other disease-modifying anti-rheumatic drugs (DMARDs) and 28 with prednisolone (<10 mg daily). For comparison, lipid levels were followed for 2 years in 70 consecutively included patients with early RA during treatment with conventional DMARDs. RESULTS: There was an initial increase in plasma levels of cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, and LDL/HDL and total/HDL cholesterol ratios. However, after 3 months HDL-cholesterol decreased significantly, followed after 6 months by cholesterol and LDL-cholesterol. The LDL/HDL and total/HDL-cholesterol ratios remained significantly raised. HDL-cholesterol increased and the ratios improved in patients with early RA receiving conventional treatment. The changes over time differed significantly between the patient groups. CONCLUSION: During infliximab infusion a pro-atherogenic lipid profile developed despite reduced inflammatory activity. The long-term decrease in HDL-cholesterol was unexpected considering the known effects of tumour necrosis factor-alpha (TNFalpha).
15997214 [Effectiveness of methotrexate for the escape by salazosulfapyridine]. 2005 Jul Although disease modifying anti-rheumatic drugs (DMARDs) are used in the treatment of rheumatoid arthritis (RA), the selection of agents in the case of relapse (escape phenomenon) lacks clear-cut standards. We compared the effectiveness in a salazosulfapyridine and then methotrexate (SASP-->MTX) group with that in the mothotrexate (SASP+MTX) group after escape phenomenon expression in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) data. Outpatients of the Matsubara Mayflower Hospital with a history of DMARD administration during the 4 years prior to May 2003 were studied. The CRP level in the SASP-->MTX group (n=8) after the escape phenomenon expression showed a decline after 3 months, but no decline was seen even after 3 months the two in the CRP level in the SASP+MTX group (n=10). However, the difference between groups was not significant. The fluctuation in ESR was similar to that in CRP. However, ESR was significantly lower in the SASP-->MTX group 20 weeks after escape phenomenon expression. In evaluating treatment effectiveness after escape phenomenon expression in each group, SASP-->MTX was effective in 10 and SASP+MTX in 7 patients. Side effects necessitated cessation of treatment in 1 patient in the SASP-->MTX group. Treatment continued in 4 patients in the SASP-->MTX group and 2 in the SASP+MTX group, even though side effects occurred. It should be borne in mind that combination therapy often has greater clinical benefit than single agent therapy but not always.
17144392 Polymorphism of HLA-DR and HLA-DQ in rheumatoid arthritis patients and clinical response t 2006 Oct OBJECTIVE: To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis (RA) and analyze the relationship between clinical response to methotrexate (MTX) and the HLA-DR and HLA-DQ genotypes in these patients. METHODS: In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers. RESULTS: There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common (p=0.015) in RA patients compared to controls. HLA-DRB1*15 was more common in patients (43.5%) compared to controls (30.8%) but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common (p = 0.01) among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1 *06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate (MTX), the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly-more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy. CONCLUSION: RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX.
16102224 B-cell lymphoma of the larynx in a patient with rheumatoid arthritis. 2005 Aug We report a case of B-cell lymphoma with the larynx as the primary site of presentation in a rheumatoid arthritis patient previously treated with methotrexate. Primary non-Hodgkin's lymphoma (NHL) of the larynx is rare. There may be an increased risk of lymphoma in patients with rheumatoid arthritis, with an even higher risk in those patients treated with methotrexate. The diagnostic and treatment options are discussed.
16343797 Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: a ca 2006 A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20+, and a portion of them was CD30+. The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein-Barr virus-encoded small RNA-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.
16052582 Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: tw 2005 Aug OBJECTIVE: To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. METHODS: This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. RESULTS: A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. CONCLUSION: Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.
15130899 A good response to early DMARD treatment of patients with rheumatoid arthritis in the firs 2005 Jan OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.