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ID PMID Title PublicationDate abstract
17164995 The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthriti 2006 The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4-10 mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.
16572442 The safety of infliximab, combined with background treatments, among patients with rheumat 2006 Apr OBJECTIVE: To assess the risk of serious infections following 22 weeks of infliximab therapy, and to further characterize the safety profile of infliximab in combination with background treatments during 1 year in patients with rheumatoid arthritis (RA) with various comorbidities. METHODS: Patients with active RA despite receiving methotrexate (MTX) were randomly assigned to receive infusions of placebo (group 1, n=363), 3 mg/kg infliximab (group 2, n=360), or 10 mg/kg infliximab (group 3, n=361) at weeks 0, 2, 6, and 14. At week 22, patients in placebo group 1 began receiving 3 mg/kg infliximab, and patients in group 3 continued to receive an infliximab dose of 10 mg/kg. Patients in group 2 who failed to meet predefined response criteria received increasing doses of infliximab in increments of 1.5 mg/kg. RESULTS: At week 22, the relative risk of developing serious infections in groups 2 and 3, compared with group 1, was 1.0 (95% confidence interval [95% CI] 0.3-3.1, P=0.995) and 3.1 (95% CI 1.2-7.9, P=0.013), respectively. The incidence of serious adverse events was 7.8% in groups 2 and 3 compared with 7.5% in group 1. From week 22 to week 54, 11.8%, 9.9%, and 10.3% of patients in groups 1, 2, and 3, respectively, reported occurrences of serious adverse events. Through week 54, 1 patient in group 1, 2 patients in group 2, and 4 patients in group 3 developed active tuberculosis. CONCLUSION: The risk of serious infections in patients receiving the approved infliximab dose of 3 mg/kg plus MTX was similar to that in patients receiving MTX alone. Patients receiving the unapproved induction regimen of 10 mg/kg infliximab plus MTX followed by a 10 mg/kg maintenance regimen had an increased risk of serious infections through week 22.
17075598 Strategies to control disease in rheumatoid arthritis with tumor necrosis factor antagonis 2006 Nov Recent data have shown that disability and joint destruction in rheumatoid arthritis (RA) occur early on in the course of the disease and progress rapidly. It has been shown that in the early stages of RA, disability is attributed to increased disease activity, whereas later in the course of the disease, disability results from irreversible joint damage. These findings support the need to develop treatment strategies that will rapidly bring the disease under control, with the ultimate goal of alleviating symptoms and halting progressive joint damage. A number of such strategies have been evaluated, including the early administration of a biologic agent alone or in combination with high-dose methotrexate. Other, more recent treatment strategies include the tight control of disease activity by targeting specific outcomes necessary for decision making; the use of biologic agents for the treatment of moderate disease; and the induction of remission with a biologic agent early in the course of disease, followed by maintenance therapy using a conventional disease-modifying antirheumatic drug. The substantial positive effect these strategies have on patient outcomes supports the concept that the optimal management of RA involves aggressive early therapy combined with close monitoring of disease progression and modification of ineffective therapeutic strategies.
16447241 Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associat 2006 Feb OBJECTIVE: Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk. METHODS: RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments. RESULTS: After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5-2.0]), including a dose-related increase in risk (< or = 5 mg/day HR 1.4 [95% confidence interval 1.1-1.6], > 5-10 mg/day HR 2.1 [95% confidence interval 1.7-2.7], > 10 mg/day HR 2.3 [95% confidence interval 1.6-3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0-1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6-110]) and sulfasalazine (0.7 [95% confidence interval 0.5-1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero. CONCLUSION: There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti-tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.
16205925 Classic disease modifying anti-rheumatic drugs (DMARDs) in combination with infliximab. Th 2006 Jun To assess the performance of infliximab in a clinical setting, 364 rheumatoid arthritis (RA) patients from the National Register of Biological Treatment in Finland (ROB-FIN) were analysed. Corticosteroid usage and dose diminished (p<0.05 and 0.001, respectively) in patients on infliximab, of whom 51% also used one, 28% two and 16% three other concomitant DMARDs. A 34% of the RA patients used methotrexate+/-corticosteroids without any other DMARD. Methotrexate was most frequently used with sulphasalazine and/or hydroxychloroquine. Non-methotrexate patients most frequently used leflunomide or azathioprine combined with corticosteroids. The clinical effect of these combinations was similar to that of infliximab with methotrexate alone. The results indicate that infliximab can be used together with other DMARDs than methotrexate alone, quite according to the philosophy of the combination drug therapy, as the effectiveness is as good as or even slightly better than that of methotrexate and infliximab.
16539813 Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumat 2006 Jan OBJECTIVE: The findings of the involvement of tissue transglutaminase (tTg) in the pathogenesis of coeliac disease (CD) have stimulated progress in the field of auto-immune diseases. Another calcium-dependent cysteine enzyme, peptidylarginine deiminase type 4 (PAD4), seems to be involved in the pathogenesis of rheumatoid arthritis (RA). There are obvious similarities between Tgs and PADs. METHODS: Using enzyme-linked immuno-sorbent assays, we have measured the occurrence of antibodies against guinea pig (gp) and human recombinant (hr) tTg, PAD and citrulline in 59 controls and 184 RA-patients, of whom 71 were treated with methotrexate (mtx). RESULTS: In addition to the expected antibodies against citrulline (62%), sera from the 113 RA-patients without mtx treatment contained significantly increased frequencies of IgG anti-PAD (35%), IgA anti-gp-tTg (34%), IgA anti-hr tTg (20%), IgG anti-gp-tTg (13%) and IgA anti-hr-FXIII (15%) compared to controls. In sera from the mtx-treated RA-patients the expression of antibodies was reduced. In patients not treated with methotrexate there was a statistically significant correlation between, on one hand, IgG anti-PAD and on the other hand, IgG anti-citrulline, IgA anti-gp-tTg, IgA anti-hr-tTg, IgG anti-gp-tTg, IgG anti-hr-tTg, or IgA anti-hr-FXIII. In the mtx-treated group these correlations were less pronounced. CONCLUSION: In addition to the expected antibodies against citrulline, sera from RA-patients contained antibodies against PAD and against Tgs of at least two kinds, indicating that the specificity for anti-tTg in CD is far from complete. Most of the patients displayed more than one antibody, a possible indication of epitope spreading. MTX-treatment reduced the expression of antibodies.
16620141 B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. 2006 Rheumatoid arthritis (RA) is a human systemic autoimmune disease with a prevalence of about 1%. Although an important role for B cells has been demonstrated in animal models of autoimmune, inflammatory arthritis, the importance of B cells in RA has been controversial for decades. The development of therapies targeting B cells may help to resolve this debate. Rituximab, a mouse-human chimeric monoclonal antibody against the B cell-specific antigen CD20, was the first B cell-targeted therapy tested in double-blind, placebo-controlled trials for RA. On the basis of the data from three separate trials, addition of rituximab to methotrexate appears to reduce significantly the signs and symptoms of rheumatoid factor-seropositive RA, as assessed by American College of Rheumatology (ACR) 20, 50 and 70 response criteria, and to be relatively safe. Significant questions about rituximab therapy still need to be addressed, including whether or not treatment with rituximab reduces radiographic progression of joint damage, the safety and efficacy of repeated courses of rituximab, and the long-term effects of rituximab on the immune system. Preliminary data on treatment of RA with belimumab, a fully human monoclonal antibody against B lymphocyte stimulator (a growth and survival factor for B cells) is now available. In a double-blind, placebo-controlled, phase II trial, belimumab was well tolerated and had a significant beneficial effect on the ACR 20 response. Thus, therapies specifically targeting B cells do appear to be effective in the treatment of RA, providing direct evidence that B cells are important in the pathogenesis of RA.
16507172 Methotrexate in rheumatoid arthritis is frequently effective, even if re-employed after a 2006 Effectiveness of therapy with individual disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is limited, and the number of available DMARDs is finite. Therefore, at some stage during the lengthy course of RA, institution of traditional DMARDs that have previously been applied may have to be reconsidered. In the present study we investigated the effectiveness of re-employed methotrexate in patients with a history of previous methotrexate failure (original course). A total of 1,490 RA patients (80% female, 59% rheumatoid factor positive) were followed from their first presentation, yielding a total of 6,470 patient-years of observation. We identified patients in whom methotrexate was re-employed after at least one intermittent course of a different DMARD. We compared reasons for discontinuation, improvement in acute phase reactants, and cumulative retention rates of methotrexate therapy between the original course of methotrexate and its re-employment. Similar analyses were peformed for other DMARDs. Methotrexate was re-employed in 86 patients. Compared with the original courses, re-employment was associated with a reduced risk for treatment termination because of ineffectiveness (P = 0.02, by McNemar test), especially if the maximum methotrexate dose of the original course had been low (<12.5 mg/week; P = 0.02, by logistic regression). In a Cox regression model, re-employed MTX was associated with a significantly reduced hazard of treatment termination compared with the original course of methotrexate, adjusting for dose and year of employment (hazard ratio 0.64, 95% confidence interval 0.42-0.97; P = 0.04). These findings were not recapitulated in analyses of re-employment of other DMARDs. Re-employment of MTX despite prior inefficacy, but not re-employment of other DMARDs, is an effective therapeutic option, especially in those patients in whom the methotrexate dose of the original course was low.
16014674 Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying dru 2006 Feb OBJECTIVE: To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers. METHODS: 82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group. RESULTS: Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.
16573354 Spotlight on infliximab in Crohn disease and rheumatoid arthritis. 2006 Infliximab (Remicade) is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha that has shown efficacy in Crohn disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2, and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn disease with an inadequate response to other treatment options or those with fistulizing disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmacoeconomic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn disease (including fistulizing disease) or rheumatoid arthritis (including early disease).
16504996 Power Doppler sonography monitoring of synovial perfusion at the wrist joints in patients 2006 Nov OBJECTIVE: To use power Doppler sonography (PDS) to evaluate changes in synovial perfusion induced by adalimumab in the wrist joints of patients with rheumatoid arthritis. METHODS: 48 wrists of 24 patients (18 women and 6 men) were examined. Despite prior treatment with disease-modifying antirheumatic drugs, including methotrexate, patients with clinically active rheumatoid arthritis were recruited in two rheumatological centres to receive 40 mg adalimumab subcutaneously every other week. Clinical, laboratory and PDS assessments were carried out at 0, 2, 6 and 12 weeks. Clinical and laboratory measurements of disease activity included physician's global assessment of disease activity, erythrocyte sedimentation rate and serum levels of C reactive protein. The Disease Activity Score for 28 joints (DAS28) was calculated. PDS signal was scored from 0 to 3 according to the overall expression of PDS findings at the wrists. RESULTS: A significant reduction in both clinical (p<0.001) and PDS findings (p<0.001) was found at all follow-up examinations. A tendency to positive correlation (Spearman's r = 0.382; p = 0.067) was shown between reduction in PDS score and improvement in DAS28 at week 2 examination. CONCLUSION: PDS detected a rapid and significant reduction in synovial perfusion at the wrist joints of patients with rheumatoid arthritis receiving adalimumab. Ongoing follow-up will provide further information regarding the persistence of considerable reduction in PDS signal score and its correlation with DAS28.
16690341 Cardiovascular risk and rheumatoid arthritis: clinical practice guidelines based on publis 2006 Jul OBJECTIVE: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts. RESULTS: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy.
16758511 Cost-effectiveness analysis of MTHFR polymorphism screening by polymerase chain reaction i 2006 Jul OBJECTIVE: To determine whether a strategy based on methylenetetrahydrofolate reductase (MTHFR) genotype screening is more cost-effective than the conventional strategy in reducing the risk of methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA). METHODS: We consecutively enrolled 385 patients with RA (355 female, 30 male) who had received MTX and identified toxicity associated with MTHFR C677T genotypes. We designed a hypothetical decision model to compare the genotype-based strategy with the conventional strategy. The time horizon was set as 1 year, and direct medical costs were used. The measured outcomes were the total expected cost, the effectiveness, and the incremental cost-effectiveness ratio. RESULTS: MTHFR genotype distribution revealed 133 patients (34.6%) with 677CC, 193 (50.1%) with 677CT, and 59 (15.3%) with 677TT. A total of 154 patients (40.0%) exhibited MTX-related toxicity. Compared to RA patients with the CC genotype, the odds ratio (95% confidence interval) for risk of toxicity was 3.8 (2.29-6.33) for the CT genotype, and 4.7 (2.40-9.04) for the TT genotype. In the base-case model, the total expected cost and the probability of continuing MTX medication for the conventional and genotype-based strategies were 851,415 Korean won (710 US dollars) and 788,664 Korean won (658 US dollars), and 94.03% and 95.58%, respectively. CONCLUSION: The MTHFR C677T polymorphism may be an important predictor of MTX-related toxicity in patients with RA. The cost-effectiveness analysis suggests that the genotype-based strategy is both less costly and more effective than the conventional strategy for MTX therapy.
16463431 Splitting high-dose oral methotrexate improves bioavailability: a pharmacokinetic study in 2006 Mar OBJECTIVE: To study the bioavailability of a divided higher oral dose of methotrexate (MTX), in comparison to a single dose, in adult patients with rheumatoid arthritis (RA). METHODS: A pharmacokinetic analysis was performed in 10 patients with RA taking a stable dose (25-35 mg weekly) of MTX. Separated by one week, a pharmacokinetic analysis was performed in each patient after an oral single dose, and after an equal but split dose separated by 8 hours. MTX serum concentrations were measured by a fluorescence polarization immunoassay technique. Analysis was performed by calculation of the area under the curve (AUC) by the trapezoidal rule and by means of an iterative 2-stage Bayesian population procedure, obtaining population and individual pharmacokinetic parameters. For the population analysis, data from 15 patients in our previous study comparing oral and subcutaneous administration of MTX were also used. RESULTS: The median MTX dose was 30 mg weekly (range 25-35 mg). The bioavailability of the split dose was 28% higher compared to the single dose (p = 0.007). In the population pharmacokinetic modeling, a 2-compartment model best described the serum MTX concentration versus time curves. The mean bioavailability after single-dose and split-dose MTX was 0.76 and 0.90, respectively, compared to subcutaneous administration. There was a statistically significant difference in the bioavailability of the 2 oral administration regimens (p = 0.008). CONCLUSION: The bioavailability of oral higher dose MTX in adult patients with RA can be improved by splitting the dose.
16652417 Controlled trial of methotrexate versus CH-1504 in the treatment of rheumatoid arthritis. 2006 May OBJECTIVE: To investigate the clinical efficacy, safety, tolerability, and toxicity profile of a metabolically stable antifolate, CH-1504, compared to methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). METHODS: A 24-week open-label trial of MTX and CH-1504 was performed in 20 patients with RA. RESULTS: Improvements in clinical and laboratory indicators were observed in both study groups. Improvement in the CH-1504 group was greater than in the MTX group. Both treatments were generally well tolerated; however, the liver function test abnormalities and gastrointestinal related adverse events expected with this class of medication were not seen with CH-1504. CONCLUSION: CH-1504 appears to be clinically efficacious and may possess a superior safety and tolerance profile compared to MTX.
15856365 West Nile virus meningitis in a chronic immunosuppressed patient with rheumatoid arthritis 2005 Sep The clinical presentation of West Nile virus (WNV) can be severe in immunosuppressed patients. A 65-year-old with steroid-dependent rheumatoid arthritis on infliximab and methotrexate presented with meningitis and profound muscular weakness. Serum WNV IgM and IgG antibody were positive. WNV should be included in the differential diagnosis of neurological symptoms in peak months.
15641062 Presentation and analysis of data on radiographic outcome in clinical trials: experience f 2005 Jan OBJECTIVE: To evaluate different methods of presentation and analysis of radiographic data in a rheumatoid arthritis (RA) randomized controlled trial. METHODS: A double-blind randomized controlled trial including 682 patients with active RA who were treated with methotrexate, etanercept, or a combination of the 2 drugs was used for this study. Probability plots of the change from baseline to year 1 were produced to visualize progression, and were compared with usual descriptive statistics. The primary analysis of the trial (based on annualized actual mean change from baseline in total Sharp score at 1 year, using linear imputation) was challenged using various ways of handling missing information with alternative imputation methods, and by various statistical analyses including analysis of covariance (ANCOVA) and mixed model analysis on both raw and log-transformed data. RESULTS: Probability plots provided detailed insight into the differentiated treatment effects between the 3 arms of this study. As adjuncts to formal hypothesis testing, these plots were more useful for presenting data than were summary descriptive statistics or use of preset cutoff points to define lack of progression. Additional analyses presented here support the results obtained with the per-protocol analysis that showed an advantage of the combination treatment compared with the monotherapy arms and for etanercept versus methotrexate alone. Various ways of handling missing information confirmed the robustness of the results. In addition, both ANCOVA and mixed model analyses on raw and on log-transformed data produced similar results. CONCLUSION: We suggest a panel of alternative analysis methods and alternative ways of handling missing information to verify that the radiographic results reported in an randomized controlled trial are not influenced by technical factors, such as interpolation, handling of missing data, and choice of statistical tests.
15660467 The anti-tumor necrosis factor agents are a major advance in the treatment of rheumatoid a 2005 Jan Despite optimization of the use of the traditional disease modifying antirheumatic drugs (DMARD) as mono- or combination therapy, between 25% and 50% of patients with rheumatoid arthritis (RA) still have clinically active synovitis with progressive structural articular damage. Several clinical trials with the anti-tumor necrosis factor (TNF) agents etanercept, infliximab, and adalimumab, used alone or in combination with methotrexate, in patients with early or established RA have shown consistent improvement in signs and symptoms as well as function, with a dramatic slowing of radiographic damage. The anti-TNF agents combined with optimal doses of MTX currently constitute the best therapeutic regimen for the management of patients with RA failing to adequately respond to traditional DMARD.
15966441 [The Jo-1 Syndrome--immunological findings and clinical manifestations]. 2005 Mar 15 El The Jo-1 syndrome is an autoimmune disease which is characterized by the presence of autoantibodies against the Jo-1 antigen. The designation Jo-1 is derived from the name of the first patient (John P.) who was tested positive for this antibody. This patient suffered from polymyositis and fibrosing alveolitis. The Jo-1 antigen was identified as histidyl-transfer-RNA synthetase present in the cytosol. The Jo-1 syndrome is a member of a family of autoimmune diseases, called anti-synthetase syndromes. These syndromes are characterized by autoantibodies directed against aminoacyl-transfer-RNA synthetases. The etiology of the Jo-1 syndrome is unknown. The most frequent clinical manifestation is myositis, which may present as polymyositis or dermatomyositis. In addition to muscle involvement, interstitial lung disease is frequently found and critical for the prognosis. Furthermore, symptoms of other autoimmune disorders such as polyarthritis may occur. Similar to polymyositis and dermatomyositis, the Jo-1 syndrome may present as myositis overlap syndrome. In these cases, antibodies against U1-RNP are detected. The Jo-1 syndrome responds to treatment with corticosteroids and, if necessary, azathioprine, methotrexate or cyclophosphamide. The clinical manifestations of the Jo-1 syndrome are illustrated by two clinical cases.
16040336 Autoantibodies profile of rheumatoid arthritis patients during treatment with infliximab. 2005 Mar PURPOSE: Therapy with TNFa blocking agents has been associated with increased rate of anti-nuclear antibodies (ANA) and rare cases of lupus like syndromes. Our aim was to prospectively analyze a wide array of autoantibodies in rheumatoid arthritis (RA) patients before and 14 weeks after starting infliximab. MATERIAL AND METHODS: In this study, 26 consecutive active RA patients participated. All treated with infliximab at a dosage of 3 mg/kg on week 0, 2, 6 and every 8 weeks, along with weekly low dose methotrexate. Patients were evaluated at week 0 and 14. Clinical assessment included the number of tender and swollen joints, duration of morning stiffness, adverse events (AE) (including SLE-like) and ESR. Sera were collected before the 1st infusion of infliximab at week 0 and 14. The autoantibodies studied were: fluorescent ANA, anti-double-stranded-DNA (anti-ds-DNA), IgG and IgM anti-cardiolipin (ACA), anti-histone- H1 and C (H1, H2A, H2B, H3, H4), anti-SSA, -SSB, -ENA, -scleroderma 70, -thyroid peroxidase (TPO) and -neutrophilic cytoplasmatic (ANCA) antibodies. RESULTS: Of 26 patients, 17 were women. A significant decrease in duration of morning stiffness, number of tender and swollen joints and ESR were observed between week 0 and 14. During follow up (mean of 20.5+/-7.3 months), 9 patients stopped infliximab due to inefficacy or AE (most of them after the 4th infusion). Two patients developed lupus-like phenomena. ANA was found positive at baseline in 7 out of 26 patients. In 5 of them, an increase in the titer of ANA was observed at week 14. ANA negative turned positive for 8 patients. A significant increase of anti-cardiolipin (ACA)-IgM levels was observed in 8 patients and of ACA-IgG in 6, in parallel with ANA seroconversion. The mean level of anti-double-stranded-DNA (anti-ds-DNA) -IgG significantly increased from 66+/-33 to 93+/-68 IU/ml, in 4 patients to pathological levels. Four patients demonstrated an increase in anti-histone H1. Levels of ANCA, anti-ENA, -SSA, -SSB, -RNP, -scleroderma70 and -thyroid peroxidase (TPO) were negative in all patients and remained unchanged during the study. Cessation of treatment with infliximab was found to be associated with the appearance of ANA. CONCLUSION: An increased titer or a new appearance of ANA was observed in 12 out of 26 patients. The main autoantibodies found were anti-ds-DNA, ACA-IgM and -IgG and anti-histone. In our cohort, the appearance of some autoantibodies seemed to predict late cessation of treatment.