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16970509 Disease-modifying antirheumatic drugs in pregnancy: current status and implications for th 2006 Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD at time of conception as well as during pregnancy. The aim of this paper was to review recent literature about DMARDs used for rheumatic diseases in pregnancy and to describe the type of study designs and results reported.Twenty-nine studies; eight on hydroxychloroquine/chloroquine, thirteen on methotrexate, three on sulfasalazine and six on azathioprine were identified. With respect to hydroxychloroquine, most studies concluded that it could be safely used in systemic lupus erythematosus or RA. The same conclusions were drawn from the azathioprine studies, but the available evidence is scarce. Although the evidence regarding the safety of methotrexate during pregnancy is conflicting, a high rate of pregnancy losses indicates a risk to the fetus. For each individual case it must be decided whether the benefits outweigh the potential risks. No major teratogenic effects of sulfasalazine were seen although teratogenic effects still can not be excluded. For all other DMARDs, the information on their use in pregnancy was limited. This review underscores the gross absence of data on safety and risks of DMARD use during conception and pregnancy. While young women use these drugs in pregnancy, this review stresses the importance of good monitoring and further research.
17009230 Disconnect between inflammation and joint destruction after treatment with etanercept plus 2006 Oct OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.
17471832 [Rational therapeutic approach in rheumatoid arthritis]. 2006 The natural course of rheumatoid arthritis inevitably leads to joint damage and reduced life expectancy. Therefore, active treatment of rheumatoid arthritis is indispensable. Although the etiology still remains unknown resulting in unsuccessful prophylaxis and incurability of rheumatoid arthritis, learning more about its pathophysiology broadens the spectrum of therapeutic possibilities. The aim of treatment is remission of the disease. Current standards of treatment are based on the idea to start aggressive treatment as early as possible to suppress the activity of the disease. This can be achieved by pharmacotherapy and rehabilitation. Physiotherapy is supplementary but there is no room for spa treatment or alternative therapies. Treatment should be introduced immediately because the "window" for successful change in the natural course of the disease covers the first three months since onset. Diagnostic difficulties during this period support the idea of "early arthritis" and "early rheumatoid arthritis". Glycocorticosteroids at a dose suitable to suppress inflammation represent the first-line treatment. Basic therapy which usually is synonymous for methotrexate 15-25 mg once weekly should be introduced from the 4th month at the latest. In case of methotrexate intolerance, leflunomide is an alternative. Lack of efficacy of monotherapy with these drugs mandates the combination therapy of methotrexate with leflunomide, cyclosporine or sulphasalazine together with hydroxychlorochine. The use of two latter drugs should be limited due to their low efficacy. Patients refractory to combination therapy should be considered as candidates to anticytokine drugs or to lymphocyte B depleting drugs. However, it should be emphasized that their high efficacy is achieved only in combination with full doses of methotrexate. The same rules should be applied to therapeutic decisions in elderly patients and in patients with long history of rheumatoid arthritis. However, lower doses of the drugs should be used at initiation of therapy. Contraindications related to side effects and concomitant diseases should be considered. In these groups, glycocorticosteroids play a more important role and cyclophosphamide is used more frequently. Surgical treatment should be reserved for patients with advanced disease. Total joint replacement is an effective method for large joints. Synovectomy should be done only exceptionally when all options of pharmacotherapy were ineffective.
18358926 Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid a 2008 Mar 22 BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.
18039681 Daily practice effectiveness of a step-down treatment in comparison with a tight step-up f 2008 Jan OBJECTIVE: To study prospectively the daily practice effectiveness of a step-down early rheumatoid arthritis (RA) treatment strategy. METHODS: Patients with severe RA and no contra-indications were proposed step-down therapy, the others step-up. Step-down patients received a modified combination therapy in early RA (COBRA) regimen: sulphasalazine (SPS), 2 g daily, and methotrexate (MTX), 15 mg weekly, combined with step-down oral prednisolone (start 60 mg daily, fast tapering to 7.5 mg over 6 weeks, discontinuation from week 28). At week 40, patients were randomized to maintenance therapy with either SPS or MTX if disease activity score-28 (DAS28) was acceptably low. The step-up group started disease-modifying anti-rheumatic drug (DMARD) monotherapy. In both groups, treatment was adjusted at follow-up, based on DAS28. DAS28, functionality Health Assessment Questionnaire (HAQ), adverse events, DMARD changes and steroid use were registered 4-monthly for 2 yrs. RESULTS: Nineteen patients received step-down and 52 step-up treatment. More patients completed the first year without unplanned DMARD changes and without dosage adjustment and fewer had DMARD changes due to side effects or inefficacy in the step-down group compared with step-up, whereas the number of adverse events was comparable. MTX proved to be the most effective maintenance therapy after step-down. The DAS response, proportion of patients in remission, HAQ response and proportion of patients without disability at 4 months was higher in the step-down group. CONCLUSIONS: In daily practice, a step-down treatment strategy for early RA is more effective than a step-up approach.
17666447 Patient-reported health outcomes in a trial of etanercept monotherapy versus combination t 2008 Aug OBJECTIVES: This study assessed the relative efficacy of etanercept (ETN) or etanercept and methotrexate (ETN+MTX) for patients with rheumatoid arthritis (RA) who had an unsatisfactory response to MTX, using patient-reported outcomes (PROs) of function, pain, general health, disease activity and morning stiffness. METHODS: The PROs were secondary assessments in a 16-week, prospective, randomised, parallel-group study conducted at 60 European centres. Patients with RA were randomly assigned either to monotherapy with ETN or combination therapy with ETN+MTX. PRO instruments administered included the Stanford Health Assessment Questionnaire, the pain visual analogue scale, the EuroQoL assessment of current health state (EQ-5D), the EQ-5D visual analogue scale, a patient global assessment of disease activity and an assessment of morning stiffness. Treatment groups were compared by percentage of patients within clinically meaningful categories. The primary endpoint for all PROs was comparison of mean improvement from baseline to week 16 between ETN and ETN+MTX groups. RESULTS: Three hundred and fifteen patients were randomised to ETN or ETN+MTX. Both treatment arms had similar Health Assessment Questionnaire Disability Index DI, EQ-5D, patient global assessment of disease activity, pain or morning stiffness scores and improvement from baseline to week 16. CONCLUSIONS: For patients with active RA and intolerance or unsatisfactory response to MTX, substituting ETN for MTX and adding ETN to MTX are both effective ways of reducing disability, pain, disease activity, morning stiffness, and improving general health.
17694260 Improvement of disease activity of rheumatoid arthritis patients from 2000 to 2006 in a la 2007 The objective of this study was to show whether the disease activity of rheumatoid arthritis (RA) patients had improved in Japan, and whether the improvement of disease activity had resulted in a better outcome of patients. In a single-institute-based prospective observational cohort of RA patients (Institute of Rheumatology, Rheumatoid Arthritis, IORRA), a total of 7512 patients were enrolled, and their information was collected biannually. A cross-sectional data set A that included all patients in each phase was analyzed. From October 2000 to April 2006, disease activity score DAS28 significantly improved from 4.15 to 3.63, and the frequency of patients in remission (DAS28 < 2.6) increased from 8.5% to 21.5%. During this period, the frequency of methotrexate users increased from 33.9% to 58.7% and the average dosage of methotrexate also increased from 5.59 mg/week to 6.94 mg/week; on the other hand, there was no increase in any adverse reaction among the methotrexate users. To investigate the relationship between longitudinal disease control and progression of disability, a longitudinal data set B that included 712 patients who completed all phases of the study from 2000 to 2006 was selected and was analyzed. The disability index JHAQ of a poorly controlled group (average DAS > 5.1) increased (+34.8%), that of a moderately controlled group (average DAS 3.2-5.1) also increased (+14.0%), but that of a well-controlled group (average DAS < 3.2) decreased (-13.0%). In conclusion, by using a prospective observational cohort IORRA in Japan, we demonstrate that RA disease activity improved from 2000 to 2006, which correlates with an increased use of methotrexate. The suppression of disease activity resulted in a better outcome for patients.
17158693 Treatment of rheumatoid arthritis. 2006 Dec 15 PURPOSE: Current and investigational treatments of rheumatoid arthritis (RA) are described. SUMMARY: The current therapies used to treat RA include nonsteroidal antiinflammatory drugs (NSAIDs), used for the management of pain and inflammation; disease-modifying antirheumatic drugs (DMARDs), used as first-line therapy for all newly diagnosed cases of RA; and biological-response modifiers, targeted agents that selectively inhibit specific molecules of the immune system. Glucocorticoids and other antirheumatic drugs are also used to treat RA. DMARDs include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. NSAIDs and glucocorticoids are effective in controlling the pain, inflammation, and stiffness related to RA. Unlike NSAIDs, they slow clinical and radiographic progression of RA. The biological-response modifiers include infliximab, etanercept, and adalimumab (inhibitors of tumor necrosis factor [TNF]-alpha); anakinra, a recombinant inhibitor of interleukin-1; abatacept, the first costimulation blocker; and rituximab, a chimeric anti-CD20 monoclonal antibody. Investigational therapies for RA include anti-interleukin-6-receptor monoclonal antibodies, new TNF-alpha inhibitors (including one for oral administration), and antibodies against proteins critical for B-cell function and survival. Data accumulated in the past decade favor early aggressive therapy for patients suspected of having RA, including early referral to a rheumatologist, new diagnostic techniques, and aggressive therapy with DMARDs, glucocorticoids, and biological agents. The benefits of this approach have been demonstrated in clinical trials. CONCLUSION: Pharmacologic treatments of RA include NSAIDs, glucocorticoids, DMARDs, and biological agents. With an improved understanding of the pathophysiology of RA and the evidence from various clinical trials with the agents, early aggressive therapy with a combination of drugs or biological agents may be warranted for the effective treatment of RA.
18597408 Automated measurement of joint space width in small joints of patients with rheumatoid art 2008 Jul OBJECTIVE: Comparison of performances of 5 (semi)automated methods in measuring joint space width (JSW) in rheumatoid arthritis. METHODS: Change in JSW was determined by 5 measurement methods on 4 radiographs per patient from 107 patients included in the COBRA trial (comparing sulfasalazine alone or in combination with methotrexate and corticosteroids). For each method the number of patients with sufficient available results was assessed (efficiency). An independent repeated measurement was carried out on a random sample of 30 patients' baseline and 1-year radiographs, to evaluate within-method reliability of change scores. Discriminatory ability (DA) of the measurement methods (between the 2 treatment arms) was compared with the DA of the Sharp-van der Heijde score (SHS) and its 2 components (erosion and JSW scores). RESULTS: The overall success rate varied widely between methods. Applying the chosen threshold of a minimum of 50% available joints with a change score per patient resulted in a success rate > 92% in 4/5 methods. Repeatability of measurements was good for most methods (intraclass correlation coefficient > or = 0.80 in 4/5 methods). Almost all measurement methods in 3 followup periods (12/14) showed a lower mean loss of JSW in patients from the intensive treatment group, although this was rarely statistically significant, confirming the known difference in structural damage. JSW as measured by the (semi)automated systems often showed higher DA than the JSW score of the SHS, but was lower than the total SHS and erosion scores. CONCLUSION: Although efficiency of the methods should be improved further, results already show good reliability and encouraging DA of most methods. Optimal information may be obtained with a combination of scoring of erosions and (semi)automated measurement of JSW.
17444583 Acute exacerbation of preexisting interstitial lung disease after administration of etaner 2007 May A 70-year-old woman with a 6-year history of seropositive rheumatoid arthritis (RA) and asymptomatic interstitial lung disease (ILD) began taking etanercept for ongoing arthritis despite treatment with methotrexate (MTX) and bucillamine. MTX was discontinued before introduction of etanercept. She developed lung injury 8 weeks after starting etanercept. Etanercept was discontinued and oral prednisolone 40 mg/day was begun, and her clinical findings gradually improved. Lung injury, although rare, is a recently noticed, potentially fatal adverse effect of all 3 licensed biological anti-tumor necrosis factor (TNF) agents. We recommend caution in the use of anti-TNF agents in elderly RA patients with preexisting ILD.
16923515 EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis r 2006 Aug A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.
16783865 Most rheumatologists are conservative in active rheumatoid arthritis despite methotrexate 2006 Jul OBJECTIVE: To evaluate the proportion of patients with rheumatoid arthritis (RA) visiting office-based rheumatologists for persistently active RA despite past or current methotrexate (MTX) treatment, and to describe the management of these patients in France in 2003. METHODS: All French rheumatologists were invited to participate in a cross-sectional postal survey. During a predetermined week, they were to include the first 2 patients seen for RA with a history of past or current MTX treatment. Adequacy of current treatment was assessed based on the 28-joint Disease Activity Score 28 (DAS28) and on current MTX and corticosteroid regimens. RESULTS: Of the 1800 French rheumatologists, 492 returned 838 assessable patient questionnaires. Mean patient age was 58 years and mean time since RA diagnosis was 10 years; 77% of patients were currently taking MTX, and 51% a corticosteroid. High dosages were noted for MTX (> 15 mg/week) in 20% of patients and for corticosteroid therapy (> 10 mg/day) in 5%. Nevertheless, 41% of patients had active RA (DAS28 score 3.2 to 5.1) and 7% had very active RA (DAS28 score > 5.1). The treatment was left unchanged in 78% of patients, and biological therapy was contemplated in only 16% of patients. CONCLUSION: Although half of MTX-treated patients with RA visiting office-based rheumatologists had active or very active disease, a change in treatment was rarely considered.
17404474 [New therapeutic strategy of rheumatoid arthritis to reach the goal of suppression of join 2007 Apr Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. The pathogenesis of RA is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now defined in more detail. Previous therapy, slow acting disease-modifying antirheumatic drugs (DMARDs) as with low-dose methotrexate (MTX) were accepted for RA and lead to a significant improvement of disease symptoms, however were unable to stop joint destruction. Recently therapeutic strategies using biologics including infliximab and etaner-cept are effective for treating RA disease activity and reduce joint destruction. Moreover it has been shown that disability and joint destruction occur early in the course of RA and progress rapidly. These findings support the hypothesis "window of opportunity for therapeutic intervention in RA" , and the aggressive therapy early in the course of RA is expected to result in the induction of remission or, perhaps most important, a chance of cure.
18823645 Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid ar 2009 Oct OBJECTIVE: To evaluate the effect of antitumor necrosis factor-alpha monoclonal antibody infliximab treatment on anemia in patients with rheumatoid arthritis (RA). METHODS: Data from patients with RA who received infliximab or placebo in the multicenter, placebo-controlled, double-blind, randomized ATTRACT, ASPIRE, and START studies were included in this post-hoc, pooled analysis. Infliximab (3 to 10 mg/kg) was administered every 4 or 8 weeks, and all patients received stable doses of methotrexate (MTX). We determined the percentage of anemic patients (baseline hemoglobin level <12 g/dL) who had an increase from baseline in hemoglobin level greater than or equal to 1 or 2 g/dL or achieved normal hemoglobin level at week 22. The association of improvement in anemia with improvement in clinical parameters was also evaluated. RESULTS: Among patients with anemia at baseline, infliximab plus MTX treatment produced a significantly greater mean (standard deviation) increase in hemoglobin level from baseline to week 22 (0.74 [1.12], P < 0.0001) than placebo plus MTX (0.30 [0.92]). Significantly (P < 0.001) greater proportions of anemic patients treated with infliximab plus MTX had either at least a 1 g/dL (40%) or at least a 2 g/dL (12%) increase in hemoglobin level from baseline to week 22 or achieved normal hemoglobin level (43%) when compared with placebo plus MTX (19, 5, and 28%, respectively). Greater improvement in hemoglobin level among infliximab plus MTX-treated patients was consistently observed across subgroups and in patients without clinical response (American College of Rheumatology 20% response criteria) at week 22. Multiple regression analysis indicated that the effect of infliximab plus MTX on anemia was independent of improvement in disease activity. CONCLUSION: Treatment with infliximab plus MTX significantly improved hemoglobin level among anemic RA patients when compared with treatment with placebo plus MTX, even after adjusting for improvement in disease activity.
17379860 Gene expression profiling of rheumatoid arthritis synovial cells treated with antirheumati 2007 Apr Nonbiological therapeutics are frequently used for the treatment of patients with rheumatoid arthritis (RA). Because the mechanisms of action of these therapeutics are unclear, the authors aimed to elucidate the molecular effects of typical antirheumatic drugs on the expression profile of RA-related genes expressed in activated synovial fibroblasts. For reasons of standardization and comparability, immortalized synovial fibroblasts derived from RA (RASF) and normal donors (NDSF) were treated with methotrexate, prednisolone, or diclofenac and used for gene expression profiling with oligonucleotide microarrays. The cytotoxicity of the antirheumatic drugs was tested in different concentrations by MTS tetrazolium assay. Genes that were differentially expressed in RASF compared to NDSF and reverted by treatment with antirheumatic drugs were verified by semiquantitative polymerase chain reaction and by chemiluminescent enzyme immunoassay. Treatment with methotrexate resulted in the reversion of the RA-related expression profile of genes associated with growth and apoptosis including insulin-like growth factor binding protein 3, retinoic acid induced 3, and caveolin 2 as well as in the re-expression of the cell adhesion molecule integrin alpha6. Prednisolone reverted the RA-related profile of genes that are known from inflammation and suppressed interleukins 1beta and 8. Low or high doses of diclofenac had no effect on the expression profile of genes related to RA in synovial fibroblasts. These data give the first insight into the mechanisms of action of common antirheumatic drugs used for the treatment of arthritides. Synovial fibroblasts reflect the disease-related pathophysiology and are useful tools for screening putative antirheumatic compounds.
17065108 Purine metabolism and clinical status of patients with rheumatoid arthritis treated with d 2006 The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.
17165000 Efficacy profile of bucillamine in rheumatoid arthritis patients in a large observational 2006 Bucillamine (Buc) is a disease-modifying antirheumatic drug (DMARD) developed in Japan, which has been used as one of the first-line DMARDs for the treatment of rheumatoid arthritis (RA) in Japan. However, direct comparison of this drug with standard DMARDs including sulfasalazine (SASP) and methotrexate (MTX) has been scarcely reported. We therefore tried to evaluate the clinical efficacy of Buc by analyzing the database from the long-term observational cohort study IORRA (previously known as J-ARAMIS). The cross-sectional analysis revealed that responses to Buc treatment were better in males, patients with shorter duration of illness, and those who were rheumatoid factor-negative. In the longitudinal analysis, although there was no marked difference among the baseline variables of patients with Buc, SASP, and MTX, the percentage of patients exhibiting moderate or good response to treatment, as rated using the European League Against Rheumatism improvement criteria, was higher in the Buc group (41.0%) than in the MTX (32.6%) and SASP groups (25.6%). These data support Buc as a candidate for being a first-line drug for the treatment of patients with RA.
17058552 Rheumatoid arthritis: new developments in biologic therapy. 2006 Jun With the development of biologic agents our therapeutic approach to rheumatoid arthritis (RA) and inflammatory diseases in general, has dramatically changed within the last few years. Biologic technically means a substance as the product of biologic system and functionally as an agent that targets specific biologic molecule. Recently a number of endogenous antigens have been identified and these are known to activate CD4+ T cells leading to production of cytokines [interleukin (IL)-1, IL-6] and tumour necrosis factor (TNF)-alpha and immunoglobulins like rheumatoid factor and expression of osteoprotegerin ligands that stimulate osteogenesis leading to joint distruction. Rheumatologists and other practitioners are facing a remarkable wave of new therapies for RA like infliximab, adalimumab, atlizumab, etanercept, anakinra, prosorbacolumn, anti-IL-6 agents, IL-10 and inferferon-r. To date combination therapy of methotrexate plus a single biologic has been widely studied with synergistic effect. Etanercept and infliximab are two biologics available in India.
16881109 Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients wi 2006 Aug OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. CONCLUSION: Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease.
19014871 DMARDS and infections in rheumatoid arthritis. 2008 Dec Patients with rheumatoid arthritis (RA) has an increased infections risk and morbidity and mortality related to infections. This increased risk may occur due to the disease itself with intrinsic cellular immunity alterations or as a results of drugs used to control the disease. The potential risk of infections related to conventional disease modifying anti-rheumatic drugs (DMARDs) is not completely clarified. Methotrexate (MTX) may increase the infectious risk, but its positive effect on disease activity results in a reduction of further risk factors for infections. Data about the increased risk of pneumonia or reactivation of silent infection remain controversial. Leflunomide (LEF) seems safe in controlled trial even if it has been associated with the onset of infections requiring hospitalization, such as pneumonia. Data about other DMARDs are scanty and the main cause of interruption of therapy is related to toxicity different from infection. Beside the general positive profile of DMARDs as for infectious risk, a careful use and tight control of the patients is recommended.