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16030080 A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic 2005 Nov INTRODUCTION: Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to treat rheumatoid arthritis (RA). Early trials showed their toxicity while recent trials suggest superior efficacy. Trials of DMARD combinations have enrolled different types of patient (early or established RA), used different designs (step-up, parallel or step-down) and utilized a range of outcome measures. We undertook a systematic review of combination DMARD therapy for RA and carried out a meta-analysis to evaluate the evidence for efficacy and toxicity. METHOD: Medline, PubMed and EmBase were searched using MESH headlines 'arthritis, rheumatoid', 'drug therapy, combination' and 'randomized controlled trial' (RCT) for papers published from 1975 to April 2004. References from published articles were also searched. Three independent assessors evaluated abstracts and selected trials for detailed examination. Trials were excluded if their quality was poor, were not published in English or studied DMARDs not licensed to treat RA. Two independent assessors extracted data. Efficacy was assessed by the numbers of patients withdrawn due to lack of efficacy. Toxicity was assessed by the numbers of patients withdrawn due to adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were calculated and meta-analysis was carried out based on a random effects model. Sensitivity analyses evaluated different treatment combinations, trial designs, study populations and outcome measures. RESULTS: Fifty-three potentially relevant RCTs were identified. Twelve were excluded due to: using unlicensed DMARDs (n = 3); reporting in journal supplements of RCTs already included (n = 2); follow-up of an earlier RCT, report of biological outcomes or pharmacokinetics (n = 5); and non-English language publications (n = 2). Forty-one RCTs were evaluated in detail and another five excluded (three open-labelled studies and two with high patient attrition); 36 studies were included in the meta-analysis. These comprised 13 step-up, 16 parallel and 7 step-down trials. Nine assessed early RA and 27 established RA. Seven added steroids to DMARD monotherapy and one study added steroids to DMARD combinations. Six assessed methotrexate (MTX) plus tumour necrosis factor (TNF) inhibitors. Overall, combination DMARD therapy was more effective than monotherapy (RR 0.35; 95% CI 0.28, 0.45) although the risk of toxicity was also slightly higher (RR 1.37; 95% CI 1.16, 1.62). Combinations of MTX with TNF inhibitors and MTX with sulphasalazine or anti-malarials showed good efficacy/toxicity ratios. CONCLUSIONS: DMARD combinations vary in their efficacy/toxicity ratio. MTX plus sulphasalazine and/or anti-malarials and MTX plus TNF inhibitors have particularly favourable benefit/risk ratios.
16366417 Methotrexate-induced acute lung injury in a patient with rheumatoid arthritis. 2005 Methotrexate (MTX)-induced acute lung injury developed in a female patient with rheumatoid arthritis. She was successfully treated with high-dose glucocorticoid therapy. During her hospital stay, the serum concentration of surfactant protein (SP)-D, which was markedly elevated on admission, was finally normalized and the disease resolved. However, the serum concentration of Klebs von den Lungen (KL)-6 remained high. Although the mechanisms of lung injury by MTX have not been well defined, serial measurements of serum SPD might be useful for the clinical evaluation of drug-induced acute lung injury.
16398426 [Analysis on symptomatic factors of rheumatoid arthritis and its correlation with therapeu 2005 Dec OBJECTIVE: To analyze the symptomatic factors of rheumatoid arthritis (RA), and to explore the correlations between these factors and the efficacy of TCM herbal and western medicinal therapies. METHODS: Four hundred and thirteen patients with confirmed diagnosis as active RA came from 9 clinical centers were randomly divided into the Western medicine (WM) treated group (n=204) and the traditional herbal medicine (CM) treated group (n=209). The scheme of WM therapy included administration of voltaren extended action tablet, methotrexate and sulfasalazine. That of CM therapy included basic treatment and medication by syndrome differentiation. Eighteen items of often seen symptoms of the patients were collected before and after treatment. The therapeutic effect was evaluated by the American College of Rheumatology 20% improvement (ACR 20) and all data were analyzed using SAS 8.2 statistical software package. The category of symptoms was analyzed by factor analysis. The correlation of changes of various common factors with the therapeutic efficacy were analyzed by one-way ANOVA test. RESULTS: Four common factors were obtained from the 18 items of symptoms, which could better reflect respectively the local status of arthritis, and symptoms of Cold-syndrome, Asthenia-syndrome and Heat-syndrome in traditional Chinese medicine (TCM). Both CM and WM therapies showed consistent effect on the common factors that reflects the state of RA, but CM therapy showed superior effect on the common factors to improve Asthenia-syndrome to that of WM therapy. CONCLUSION: Factor analysis could be used to categorize and study the important factor symptoms in the syndrome differentiation of TCM, and the results of factor analysis were in accord with the category of TCM syndrome differentiation. The exploration on the correlation of common factor and therapeutic efficacy could better exhibit the characteristics of TCM efficacy.
17114190 A randomised, double-blind, placebo-controlled trial of a recombinant version of human alp 2007 May BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.
16267598 The incidence of Proteus mirabilis infection increases in patients on treatment but does n 2006 Jul The aim of this study is to determine whether treatment increases the levels of anti-Proteus antibodies (APA) in patients with rheumatoid arthritis (RA). The blood samples of 32 patients suffering from RA who were recruited in our previous study and continued to participate in our follow-up study were collected after 1 year. Their first and follow-up samples were analysed for the presence of IgG isotype and total immunoglobulins (IgG+IgA+IgM) against Proteus mirabalis (PM) using enzyme-linked immunosorbent assay with two kinds of antigen preparations: whole bacteria and sodium dodecyl sulphate (SDS) lysed bacterial extract. All patients were treated with methotrexate and hydroxychloroquine with adequate dose of non-steroidal anti-inflammatory drug. After 1 year, 11 patients were in clinical remission [erythrocyte sedimentation rate (ESR) less than 30 mm/h and C-reactive protein (CRP) less than or equal to 10 mg/l], while the rest of the 21 were in the state of active disease. Correlation and Student's t test were used for statistical analysis. APA titres were significantly elevated in patients after 1 year of therapy. However, the rise was not different between patients who were in clinical remission and those in the state of active disease. APA titre increases in the treatment of RA, and the probable mechanisms are discussed.
16760833 [Cutaneous vasculitis with necrotic ulcers in rheumatoid arthritis: treatment with anti-TN 2006 May INTRODUCTION: Anti-TNFalpha has occasionally been used in the treatment of recalcitrant forms of systemic vasculitis such as Behçet's disease, Wegener's granulomatosis and Churg-Strauss syndrome. We report on the outcome of treatment in rheumatoid arthritis patients with cutaneous vasculitis lesions on anti-TNFalpha. OBSERVATIONS: Two patients with rheumatoid arthritis present for several years had necrotic ulcers of the lower limbs due to cutaneous vasculitis. After the failure of various immunosuppressive drugs (cyclophosphamide, azathioprine, methotrexate), the two patients were treated with anti-TNFalpha: infliximab in the first case and adalimumab in the second. Cutaneous ulcers healed within two to four months of the start of anti-TNFalpha treatment. Despite ongoing anti-TNFalpha treatment, these cutaneous ulcers relapsed four to six months after complete healing. CONCLUSION: Initially spectacular healing of cutaneous vasculitis ulcers under anti-TNF alpha treatment followed by relapse after several months of treatment is suggestive of an escape mechanism.
16013933 [Infliximab in rheumatoid arthritis-use in a third level hospital]. 2005 Mar OBJECTIVES: To study the conditions of infliximab use in rheumatoid arthritis, as well as the effectiveness and adverse effects of this therapy, and to perform an economic assessment of infliximab therapy in a third-level hospital. MATERIAL AND METHODS: A retrospective study was performed including patients treated with infliximab from January 2001 to March 2003. RESULTS: Twenty-five percent of patients received doses greater than 3 mg/kg, and 12% of them at intervals shorter than 8 weeks; 78% also received methotrexate concurrently. Adverse effects reported were similar in type to those described in the pro-duct's data sheet. Regarding therapy effectiveness, objective para-meters were seen to improve, less so the remaining parameters. Therapy cost was 5.6% of day hospital costs. CONCLUSIONS: Anti-TNF drugs are a relevant alternative in the treatment of rheumatoid arthritis because of their effectiveness-safety profile, but understanding their frame of use and following recommendations issued by scientific societies are important considerations.
16570441 [Clinical observation on treatment of rheumatoid arthritis with cake-separated mild moxibu 2006 Mar OBJECTIVE: To observe the effect-increasing action of cake-separated mild moxibustion on rheumatoid arthritis (RA), and to probe a new method for RA. METHODS: Sixty cases were randomly divided into 2 groups. The control group (n=30) were treated with oral administration of methotrexate (MTX) as basic treatment, and non-steroid anti-inflammatory agents (NSAIDs) according to conditions of the patient. The treatment group (n=30) were treated with the same treatment as the control group, and Fuzi case-separated moxibustion at Guanyuan (CV 4) and Zusanli (ST 36) was added. They were treated for 3 months. RESULTS: After treatment of 3 months, the total effective rate was 83.3% in the treatment group, which was higher than 60.0% in the control group (P < 0.05); there were significant differences before and after treatment in all indexes in the two groups (P < 0.05 or P < 0.01); the ratio of the patients who completely withdrew NSAIDs in the treatment group was significantly higher than that in the control group (P < 0.05); the rate of adverse reaction in the treatment group was significantly lower than that in the control group (P < 0.05). CONCLUSION: Fuzi cake-separated mild moxibustion can increase clinical therapeutic effect on RA and reduce dosage of NSAIDs.
16265689 Staphylococcus aureus in patients with rheumatoid arthritis under conventional and anti-tu 2005 Nov OBJECTIVE: To compare the prevalence of nasal and oral Staphylococcus aureus in patients with rheumatoid arthritis (RA) with the prevalence in controls with other rheumatic diseases, and to determine predictors of S. aureus carriage and the influence of treatment with anti-tumor necrosis factor-a (anti-TNF-alpha) agents. METHODS: Eighty-one patients with RA and 83 other control patients of 2 outpatient rheumatology clinics were cultured for nasal and oral carriage of S. aureus. Quantitative nasal cultures for S. aureus were performed from swabs of the anterior nares, the posterior pharynx, and the soft palate. Information on medications, medical conditions, and risk factors for S. aureus carriage was collected from all participants by a questionnaire and confirmed by chart review. RESULTS: The S. aureus carriage rate (nasal and/or oral colonization) was 34.6% among RA patients and 32.5% among controls (p = 0.87). Being treated with an anti-TNF-alpha agent plus methotrexate (MTX) was the only independent predictor of S. aureus carriage (OR 3.24, 95% CI 1.16-9.05, p = 0.025). The S. aureus carriage rate among RA patients treated with an anti-TNF-alpha agent plus MTX was 60% (9/15) versus 23.1% (3/13) in RA patients treated with an anti-TNF-alpha agent only (p = 0.049). All S. aureus isolates were susceptible to oxacillin. CONCLUSION: The S. aureus carriage rate among patients with RA was not higher than among controls. Treatment with anti-TNF-alpha agents was not associated with an increased S. aureus carriage rate. However, treatment with an anti-TNF-alpha agent plus MTX may predispose patients to S. aureus carriage.
16645972 Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. 2006 May OBJECTIVE: Spontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease-modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population-based epidemiologic study. METHODS: A cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case-control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use. RESULTS: There were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1-3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4-3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2-5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD. CONCLUSION: The reports of ILD associated with leflunomide use are likely the result of channeling of high-risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.
15751034 A de novo, apparently balanced reciprocal translocation in a child with developmental dela 2005 Apr BACKGROUND: Methotrexate is a proven teratogen and its use periconceptually is strongly advised against. Concerns about possible chromosomal effects in the offspring of women treated with this agent have been raised, but they have not been reported. In vivo and in vitro studies have supported this possibility, however. CASE: A 32-year-old primigravida was treated with low-dose methotrexate for rheumatoid arthritis from prior to conception until six weeks postconception. Her child was born without congenital malformations but subsequently developed seizures and was diagnosed with developmental delay. He was found to have a de novo, apparently balanced, reciprocal translocation between chromosomes 5 and 20 (46,XY,t(5:20)(q15;p12)). Other investigations failed to reveal another cause for his developmental delay. CONCLUSIONS: The possible association between maternal methotrexate exposure and a de novo chromosomal anomaly in an offspring supports the recommendation that women should be advised to cease taking this drug for at least six months prior to conception.
17134602 [Rituximab (MabThera) as treatment of active rheumatoid arthritis]. 2006 Nov 20 Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with a two-week interval and in combination with methotrexate. Mild to moderate side-effects are frequent, particularly during the first infusion, but long-term side-effects are generally rare, although pulmonary events and reactivation of viral infections of the liver is of concern.
16126800 An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 exp 2006 Apr OBJECTIVE: To explore the safety, efficacy, and lymphocyte activation of a triple therapeutic regimen with infliximab, methotrexate (MTX), and ciclosporin A (CsA) by an open label, pilot study. PATIENTS AND METHODS: 19 patients (mean age 52.9 years) with active rheumatoid arthritis (mean DAS28 7.3) after a mean of 16.8 infliximab infusions and dose adjustments of both infliximab and MTX were enrolled. CsA was added to a stable therapeutic regimen. Disease activity was evaluated by the DAS28. Lymphocyte activation was evaluated by assessing CD25 expression on peripheral blood mononuclear cells (PBMCs). Primary end points were safety and efficacy according to the EULAR response criteria at 24 weeks. RESULTS: Eight patients (42%) discontinued treatment: adverse events (3), inefficacy (2) or non-compliance (2). One patient had a stroke and died. 5/11 (45%) patients who completed 24 weeks' treatment were moderate responders. CD25 expression, both on unstimulated and phytohaemagglutinin stimulated PBMCs in five patients assessed, was reduced (mean (SD) values from 37 (34)% to 15 (10)% and from 50 (15)% to 29 (20)%, respectively). CONCLUSION: In this group of patients with refractory, highly active disease, addition of CsA reduced lymphocyte activation, and resulted in a modest response and a high rate of discontinuation. In such patients, other new approaches need to be explored.
15789884 The ability of disease modifying antirheumatic drugs to induce and maintain improvement in 2005 Jan OBJECTIVE: The effectiveness of the disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), bucillamine (BUC), salazosulphapyridine (SASP) and gold sodium thiomalate (GST) over two courses of treatment with a follow-up period of at least 12 months was evaluated in 425 patients with rheumatoid arthritis. METHODS: Clinical efficacy was evaluated on the basis of the numbers of painful and swollen joints, morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels before and after treatment. Results were evaluated on the basis of the survival rate (Kaplan-Meier method) and the incidence and types of adverse drug reactions (ADR) following single and combined therapies. RESULTS: In the first course of treatment, the survival rates for MTX, GST, BUC and SASP were 52.3%, 40.4%, 33.0% and 24.8%, respectively. The rates of development of ADR were 22.9%, 23.5%, 26.3% and 30.0% for BUC, SASP, GST and MTX, respectively. In the second course, the survival rates for MTX, BUC and SASP were 36.6%, 14.1% and 10%, respectively. CONCLUSION: DMARDs used in the first course of treatment improved the clinical parameters until the 6th month after initiation of treatment. Combination treatments showed some effectiveness, but because of the high incidence of ADR the survival rate was low. DMARDs used in the second course of treatment were not efficacious and there was no improvement in the survival rate compared to the first course of treatment.
16264061 Optic neuritis with concurrent etanercept and isoniazid therapy. 2005 Dec OBJECTIVE: To report a case of optic neuritis associated with concurrent etanercept and isoniazid therapy. CASE SUMMARY: A 55-year-old man diagnosed as having rheumatoid arthritis had received treatment with nonsteroidal antiinflammatory drugs, sulfasalazine, oral methotrexate, leflunomide, and deflazacort. Four months prior to admission, he had a Disease Activity Score of 6.06; treatment with etanercept was considered. Three months prior to admission, because of evidence of latent tuberculosis, isoniazid 300 mg once daily and pyridoxine 50 mg once daily were prescribed. Treatment with subcutaneous etanercept 25 mg twice weekly was started 5 days after isoniazid was initiated. Two weeks prior to admission, the patient developed blurred vision in his left eye. Ten days later, his vision worsened and he was hospitalized. The visual acuity in both eyes was 0.7, and a campimetric examination was compatible with optic neuritis. Magnetic resonance imaging of the brain revealed lesions suggesting demyelinating lesions. The clinical course was consistent with bilateral optic neuritis. Etanercept was stopped, and isoniazid was replaced with rifampin 600 mg once daily. The patient was treated with intravenous methylprednisolone hemisuccinate 1 g/day for 5 days followed by oral prednisolone, resulting in a minor subjective improvement in left eye visual acuity. He then received oral prednisone for 3 weeks, slowly tapering to discontinuation. DISCUSSION: No physiologic factors could have predisposed this patient to develop optic neuritis. He was not diagnosed with a demyelinating disease or underlying systemic condition. The optic neuritis was unlikely to be an early manifestation of multiple sclerosis based on the clinical course and the negative results of the imaging tests. Furthermore, there was a close temporal correlation between the drug exposure and the onset of symptoms. After discontinuation of etanercept and isoniazid therapy, the patient's general condition improved. Use of the Naranjo probability scale indicated a possible relationship between optic neuritis and combined etanercept-isoniazid therapy. CONCLUSIONS: Patients initiated on etanercept and isoniazid should be closely monitored for the development of adverse neurologic signs and effects. If optic neuritis is determined, etanercept and isoniazid should be discontinued immediately.
16342095 Pattern of infliximab utilization in rheumatoid arthritis patients at an academic medical 2005 Dec 15 OBJECTIVE: To investigate the pattern of use of infliximab with an emphasis on treatment escalation and the durability of infliximab use in the management of rheumatoid arthritis (RA) in an academic setting. METHODS: We conducted a retrospective review of pharmacy and medical records of 183 patients with RA who received at least 1 infliximab infusion at the infusion centers of the Brigham and Women's Hospital. Treatment escalation was defined as an increase in the dosage of infliximab to >3 mg/kg and/or a decrease in the dosing interval to <7 weeks between infusions. RESULTS: A total of 183 patients with RA received infliximab infusions for a mean +/- SD duration of 58.2 +/- 56.6 weeks. Infliximab was discontinued in 48% of the patients during the first year of therapy and in 67% of the patients overall. A total of 126 patients had a treatment escalation, including 25 patients with a dose increase, 35 patients with a decrease in the interval, and 66 patients with both. Infliximab treatment was associated with a decrease in corticosteroid and methotrexate doses. Patients who had a treatment escalation were more likely to continue infliximab infusions compared with patients without a treatment escalation (odds ratio 2.0, 95% confidence interval 1.0-4.1). CONCLUSION: The use of infliximab may be an effective treatment for RA; however, a substantial number of patients will discontinue its use. Treatment escalation is commonly used in the management of RA with infliximab and is associated with longer duration of infliximab use.
16652418 Safety of infliximab used in combination with leflunomide or azathioprine in daily clinica 2006 May OBJECTIVE: To investigate the safety of infliximab (INF) combination therapy with leflunomide (LEF) or azathioprine (AZA) in patients with rheumatoid arthritis (RA). METHOD: A standardized questionnaire on the use of INF in combination with LEF or AZA was mailed to hospital physicians and collected over a 2 month period. Adverse events (AE) and the reasons for withdrawal of combination therapy were analyzed. RESULTS: Data on 225 patients with RA were collected retrospectively. INF was used in combination with LEF in 171 patients and with AZA in 54. The duration of INF exposure was similar in both groups (mean 8.8 mo). AE were reported in 75 patients (33.3%), 60 LEF/INF (35%) and 15 AZA/INF combinations (27.8%) (p=nonsignificant). No unexpected AE were observed. The main AE were infections (6.2%), cytopenia (5.8%), hepatotoxicity (5.8%), reactions to infusion (5.3%), and skin reactions (4%). At the time the questionnaires were sent out, 161 patients were continuing combination therapies. The main reasons for drug withdrawal were AE (53 patients, 23.5%), inefficacy (10 patients, 4%), and one temporary discontinuation for surgery. CONCLUSION: Our study suggests that INF used in combination with LEF or AZA could be an alternative to methotrexate/INF combinations.
16906016 HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. 2006 Sep OBJECTIVE: Methotrexate (MTX) represents the antirheumatic drug mainly used in rheumatoid arthritis (RA). HLA-G antigens are inducible nonclassical major histocompatibility complex class Ib molecules important for maintaining anti-inflammatory conditions. The HLA-G gene is characterized by a deletion/insertion polymorphism of 14 bp that controls specific mRNA stability and protein levels. It has been reported that MTX therapy mediates an increase of interleukin-10-producing cells. This cytokine up-regulates HLA-G expression. For this, we tested the hypothesis of an MTX-mediated HLA-G production and the possible relationship with the HLA-G 14-bp polymorphism. METHODS: Peripheral blood mononuclear cells from healthy individuals and non-MTX-treated RA patients were activated with different MTX concentrations, and soluble HLA-G (sHLA-G) and interleukin-10 production was investigated by specific immunoenzymatic assay. HLA-G 14-bp polymorphism genotyping was performed in healthy individuals and RA patients, defined as 'responders' and 'nonresponders' to the MTX therapy. RESULTS: MTX activation induces the production of sHLA-G molecules. A significant association was observed between the highest sHLA-G1 concentrations and the -14/-14 bp genotype. The analysis of the HLA-G 14-bp polymorphism in MTX-treated RA patients has confirmed an increase of the -14/-14 bp genotype in the responder group (chi=6.12, P=0.02; chi test) (odds ratio=2.46 (95% confidence interval, 1.26-4.84) P=0.009; logistic regression model). CONCLUSION: Our results propose that the MTX induces the production of the anti-inflammatory sHLA-G molecules that concur with the therapy response. Furthermore, the association between -14/-14 bp genotype and MTX clinical outcome proposes this polymorphism as a therapy marker in the early phases of the disease.
16626993 Methotrexate therapy for rheumatoid arthritis: clinical practice guidelines based on publi 2006 Jul OBJECTIVES: To develop clinical practice guidelines for the use of methotrexate in rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing recommendations. Evidence providing answers to the five questions was sought in the Cochrane databases, PubMed, and proceedings of meetings of the French Society for Rheumatology, European League Against Rheumatism, and American College of Rheumatology. Using this evidence, a group of rheumatologists developed and validated the recommendations. For each recommendation, the level of evidence and the extent of agreement among experts were specified. RESULTS: The recommendations were as follows: 1: The starting dosage for methotrexate in patients with RA should not be less than 10 mg/week and should be determined based on disease severity and patient-related factors; 2: When a patient with RA shows an inadequate response to methotrexate, the dosage should be increased at intervals of 6 weeks, up to 20 mg/week, according to tolerance and patient-related factors; 3: When starting methotrexate treatment in a patient with RA, preference should be given to the oral route. A switch to the intramuscular or subcutaneous route should be considered in patients with poor compliance, inadequate effectiveness, or gastrointestinal side effects; 4: At present, there is no evidence indicating that a change in methotrexate dosage is in order when a TNF antagonist is given concomitantly; 5: The investigations that are mandatory before starting methotrexate therapy in a patient with RA consist of a full blood cell count, serum transaminase levels, serum creatinine with computation of creatinine clearance, and a chest radiograph. In addition, serological tests for the hepatitis viruses B and C and a serum albumin assay are recommended. In patients with a history of respiratory disease or current respiratory symptoms, lung function tests with determination of the diffusing capacity for carbon monoxide are recommended; 6: Investigations that are mandatory for monitoring methotrexate therapy in patients with RA consist of full blood cell counts and serum transaminase and creatinine assays. These tests should be obtained at least once a month for the first 3 months then every 4-12 weeks; 7: Folate supplementation can be given routinely to patients treated with methotrexate for RA. In practice, a minimal dosage of 5 mg of folic acid once a week, at a distance from the methotrexate dose, is appropriate; 8: In the event of respiratory symptoms possibly related to methotrexate toxicity, the drug must be stopped and symptom severity evaluated. Should evidence of serious disease be found, the patient should be admitted immediately or advice from a pulmonologist should be obtained immediately. CONCLUSION: Recommendations about methotrexate therapy for RA were developed. These recommendations should help to improve practice uniformity and, ultimately, to improve the management of RA.
16856547 [Therapeutic agents for rheumatoid arthritis: infliximab (a chimeric human IgG 1 monoclona 2006 Jul Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The agents, interfering specifically with the cytokine, have been produced to ameliorate disease activity of RA. There are only two reagents available in the Japanese market. Infliximab, a chimeric (mouse/human) IgG 1 monoclonal antibody to TNF-alpha, shows better efficacy in the combination with methotrexate (MTX) which reduces antichimeric molecule antibody responses in the RA therapy. Etanercept is a soluble form of human TNF type II receptor linked to an IgG 1-Fc moietry. Both TNF-alpha antagonists demonstrated excellent clinical efficacy and the addition of MTX at the early phase from the onset protected bone destruction. Infections are most frequent in their adverse effects.