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ID PMID Title PublicationDate abstract
19432131 [Indications for and use of biologics in early rheumatoid arthritis based on the evidence] 2009 May Given the recent consensus that main goal of therapy for rheumatoid arthritis (RA) is remission, it is extensively studied how to get remission effectively and early. Initial treatment with biologics along with methotrexate (MTX) has been shown to achieve clinical remission much greater than that with MTX alone, suggesting that early intervention with biologics plus MTX should be seriously considered. In this regard, personalized strategy to start biologics in individual patients based on the disease activity and prognosis factors has been proposed. In this review, indication and use of biologics in early RA are discussed by showing the clinical studies published in the literature.
20889601 Disease activity, physical function, and radiographic progression after longterm therapy w 2010 Nov OBJECTIVE: To evaluate the efficacy and safety of initial combination treatment with adalimumab (ADA) and methotrexate (MTX) versus monotherapy with ADA or MTX during an open-label extension of PREMIER. METHODS: Patients with early rheumatoid arthritis (RA) received blinded ADA plus MTX, ADA alone, or MTX alone for 2 years in PREMIER. At Year 2, patients could enroll in an open-label extension and receive ADA monotherapy; MTX could be added at the investigator's discretion. Longterm efficacy results are presented as observed data. RESULTS: In the open-label period, 497 of the original 799 randomized patients had ≥ 1 dose of ADA (by original randomization: ADA plus MTX, n = 183; ADA, n = 159; MTX, n = 155). In the completers cohort [patients with available Year-5 ACR responses and modified total Sharp scores (mTSS)], the Year-5 mean change from baseline in mTSS for the ADA+MTX arm (n = 124) was 2.9, compared with 8.7 and 9.7 in the ADA (n = 115) and MTX (n = 115) arms. Comprehensive disease remission, defined as the combination of DAS28 remission, normal function (Health Assessment Questionnaire ≤ 0.5), and radiographic nonprogression (ΔmTSS ≤ 0.5), was achieved by more patients in the initial ADA+MTX arm (35%) than in the ADA (13%) or MTX (14%) arms. CONCLUSION: Initial combination treatment with ADA plus MTX, followed by open-label ADA, led to better longterm clinical, functional, and radiographic outcomes than either initial ADA or MTX monotherapy during 5 years of treatment.
20732649 Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and 2010 Aug CP-690,550 is an orally active and selective inhibitor of the janus kinase (JAK) molecules. The molecular pathways through which the JAK moieties function are described along with the clinical mechanisms associated with their inhibition. Animal models of JAK inhibition are reviewed as a background for the possible inhibition of JAK in humans. The pharmacokinetics of CP-690,550 in humans is described, and the Phase IIA and IIB trials are reviewed in some detail. These trials were dose-ranging and showed a general dose response with relatively robust American College of Rheumatology 20 (ACR20) responses. A proof-of-concept 6-week trial in which CP-690,550 was given as monotherapy was associated with highly efficacious responses at the mid and higher twice-daily dose ranges employed. A subsequent 24 week dose-ranging trial in which CP-690,550 was administered in combination with methotrexate showed ACR20 responses, which were also statistically significant versus placebo interventions. CP-690,550 treatment was associated with side effects, which included headache and nausea. Infections were more common versus placebo as were elevations in transaminase enzymes when administered in combination with methotrexate, and increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. Decreases in haemoglobin and white blood cell (WBC) counts were also observed along with small increases in serum creatinine. Occasional significant decreases of haemoglobin (>2 g dl(-1)) were observed, although decreases of WBC to less than 1000 per mm(3) were not seen. Plans for long-term follow-up of the described trials are described along with the features of five presently ongoing Phase III trials of the CP-690,550 janus kinase (JAK) inhibitor. Future directions include completion and publication of these trials along with study of JAK inhibition for other indications.
20391513 Denosumab-mediated increase in hand bone mineral density associated with decreased progres 2010 Apr OBJECTIVE: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. METHODS: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). RESULTS: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. CONCLUSION: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.
20430577 Response times follow lognormal or gamma distribution in arthritis patients. 2010 Dec OBJECTIVE: This study evaluated the statistical distribution of time to treatment response in patients with rheumatic diseases. STUDY DESIGN AND SETTING: The study used a secondary data analysis design. Data from the trial of etanercept and methotrexate with radiographic patient outcomes were used to model the response times for etanercept (ETN), methotrexate (MTX), and combined ETN+MTX in patients with rheumatoid arthritis. The German etanercept registry was used to evaluate the response time distributions in patients with juvenile idiopathic arthritis. RESULTS: For MTX, the lognormal distribution was considered to be the best model for the outcome American College of Rheumatology (ACR20), lognormal, generalized gamma, and log-logistic distributions for ACR50, and lognormal and generalized gamma for ACR70. For ETN, the lognormal model was best for ACR20, the generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For combined treatment, the best model was the log-logistic distribution for ACR20, generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For the German etanercept registry, the lognormal distribution was the best model for all three outcomes of pediatric ACR30, ACR50, and ACR70 without interval censoring. CONCLUSION: Study designs might be more efficient if the response distributions are taken into consideration during planning.
19741011 Evaluation of two strategies (initial methotrexate monotherapy vs its combination with ada 2009 Nov OBJECTIVES: In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status. METHODS: Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28(ESR)) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR) <3.2). RESULTS: From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups. CONCLUSIONS: Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.
18979150 Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with 2009 We investigated the clinical efficacy and safety of tocilizumab (a humanized anti-IL-6 receptor antibody) monotherapy in active rheumatoid arthritis (RA) patients with an inadequate response to low dose methotrexate (MTX). In a multicenter, double-blind, randomized, controlled trial, 125 patients were allocated to receive either tocilizumab 8 mg/kg every 4 weeks plus MTX placebo (tocilizumab group) or tocilizumab placebo plus MTX 8 mg/week (control group) for 24 weeks. The clinical responses were measured using the American College of Rheumatology (ACR) criteria and the Disease Activity Score in 28 joints. Serum vascular endothelial growth factor (VEGF) levels were also monitored. At week 24, 25.0% in the control group and 80.3% in the tocilizumab group achieved ACR20 response. The tocilizumab group showed superior ACR response criteria over control at all time points. Additionally, serum VEGF levels were significantly decreased by tocilizumab treatment. The overall incidences of adverse events (AEs) were 72 and 92% (serious AEs: 4.7 and 6.6%; serious infections: 1.6 and 3.3%) in the control and the tocilizumab groups, respectively. All serious adverse events improved by adequate treatment. Tocilizumab monotherapy was well tolerated and provided an excellent clinical benefit in active RA patients with an inadequate response to low dose MTX.
19074177 Evaluation of different methods used to assess disease activity in rheumatoid arthritis: a 2009 Apr OBJECTIVES: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. METHODS: 424 active (abatacept approximately 10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. METHOD: of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28 or=2). More stringent criteria (at least ACR50/LDAS), faster onset (3 visits) of ACR50/LDAS best reflected patient satisfaction (positive LR >10). CONCLUSIONS: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.
21044433 Optimal administration and dosage of methotrexate. 2010 Sep Methotrexate (MTX) has been used for the treatment of rheumatic diseases, especially rheumatoid arthritis (RA), for some decades now. Although it had been known from pharmacokinetic studies for quite some time already that the bioavailability of MTX is superior when administered parenterally rather than orally, this had never been formally proven to be clinically relevant. In a recent randomised clinical trial, the two ways of administration have been directly compared. The fact that the patient group that received MTX s.c. had better clinical outcome than the oral group can be considered as proof that this hypothesis has now been confirmed. Although this result does not mean that every patient will be in need of parenteral administration of MTX, it suggests that very active patients and those with a worse prognosis may have more benefit from this strategy.
20383728 Contribution of HLA-DRB1*04 alleles and anti-cyclic citrullinated antibodies to developmen 2010 Dec This study was intended to evaluate HLA-DRB1 alleles and antibodies against anti-cyclic citrullinated peptides (anti-CCP Abs) for their value in predicting patient responses to treatment with disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). The subjects were 124 Japanese patients who had received their first treatment with DMARDs, usually methotrexate, within 1 year of disease onset and who had been followed-up for 2 years subsequently. Approximately 40% of patients developed DMARD resistance and accordingly required anti-tumor necrosis factor α (TNFα) therapy during the 2-year period. DMARD resistance was strongly associated with the carriage of SE-positive HLA-DRB1*04 alleles, especially the *0405 allele (OR, 3.92; 95%CI, 1.83-8.41; p = 0.0003). In contrast, the SE-positive allele HLA-DRB1*0101 was less potent in contributing to DMARD resistance. The rate of anti-CCP Ab-positive patients was significantly higher in the DMARD-resistant group (OR, 6.62; 95%CI, 1.45-30.24; p = 0.008). Multivariate logistic regression analysis confirmed the strong association of DMARD resistance with the presence of SE-positive *04 alleles (OR, 2.89; 95%CI, 1.28-6.53; p = 0.011) and anti-CCP Abs (OR, 6.31; 95%CI, 1.23-32.34; p = 0.027), yielding an area under the receiver operating characteristic curve of 0.76 (95% CI, 0.68-0.84; p = 0.000). After stratification, the highest rate of DMARD resistance was observed in patients having both SE-positive *04 alleles and anti-CCP Abs. These observations show that the presence of SE-positive *04 alleles in combination with anti-CCP Abs is the strongest predictor for development of DMARD resistance and eventual need of anti-TNFα agents in patients with early RA.
20665252 Epstein-Barr virus-infected subcutaneous panniculitis-like T-cell lymphoma associated with 2010 Sep Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in patients treated with MTX. We report a case of Epstein-Barr virus (EBV)-positive subcutaneous panniculitis-like T-cell lymphoma (SPTCL) in a 60-year-old Japanese man treated with MTX for rheumatoid arthritis (RA). SPTCL is a rare cytotoxic T-cell lymphoma characterized by involvement of subcutaneous fat mimicking panniculitis. The patient, who had been on MTX therapy for RA, manifested high fever and lumbago. Physical examination showed multiple subcutaneous nodules on the trunk including axillary and inguinal regions. Biopsy of the inguinal nodule showed profuse infiltration of CD8(+) T-cell lymphoma cells in the subcutaneous adipose tissues. A diagnosis of SPTCL was made according to the diagnostic criteria of World Health Organization classification. EBV-encoded small RNA in situ hybridization revealed that the lymphoma cells contained EBV genome. The cells were positive for EBV latent membrane protein 1, but not for EBNA2. After discontinuation of MTX, the nodules regressed spontaneously. Studies have reported that most MTX-LPDs are B-cell type lymphomas and Hodgkin lymphoma. To the best of our knowledge, EBV-positive SPTCL has not been reported in patients receiving MTX. Our case emphasizes the importance of clinical and virological characterization of MTX-associated SPTCL.
18593759 Radiographic changes in rheumatoid arthritis patients attaining different disease activity 2009 Jun OBJECTIVE: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. METHODS: Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (< or =3.3), low (>3.3 to < or =11), moderate (>11 to < or =26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. RESULTS: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. CONCLUSION: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.
20382605 The effect of anti-tumor necrosis factor (TNF)-alpha therapy with etanercept on endothelia 2010 Apr OBJECTIVE: To investigate the effects of tumor necrosis factor (TNF)- alpha antagonism with etanercept (ENC) on endothelial functions in patients with active rheumatoid arthritis (RA). METHODS: A total of 21 patients with RA were enrolled in this prospective study. Eleven of them (8 women, 3 men mean age 47.0+/-10.1 years) with high disease activity despite the conventional treatment were assigned to Group 1 and were given ENC treatment twice a week (25 mg SC injection) for 12 weeks. Ten patients with RA (8 women, 2 men mean age 55.0+/-6.4 years) under conventional methotrexate and prednisone therapy were assigned as Control group (Group 2). Endothelium-dependent and -independent vasodilator responses of the brachial artery were assessed by high-resolution ultrasound. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured at baseline and at the post treatment period. Mann-Whitney U and Wilcoxon tests were used to compare the data and correlation analysis was performed using Pearson correlation test. RESULTS: Endothelium-dependent vasodilatation improved from 5.2+/-0.8% to 7.9+/-1.3% (p=0.04) in ENC group, while no significant change was observed in the control group (from 6.6+/-1.1% to 7.0+/-1.8% p=0.67). No significant changes were found in endothelium-independent vasodilatation and baseline brachial artery diameters in both groups. A significant reduction in ESR and CRP were observed in patients receiving ENC (from 16.2+/-6.8 to 9.2+/-5.1 mm/h, p=0.003 and from 14.68+/-3.4 to 9.25+/-3.7 mg/L, p=0.003, respectively). CONCLUSION: Treatment with ENC for 12 weeks significantly improved endothelial function in patients with active RA compared to those under conventional therapy. The findings of the present study support the hypothesis that the use of TNF-alpha blockers in patients with active RA may reduce the high incidence of cardiovascular complications.
19772799 Methotrexate information booklet study 2008. 2009 Jul INTRODUCTION: I n order to assess the value of using the methotrexate information booklet, we conducted a single blind prospective controlled trial of the patients attending two rheumatology services. METHODS: The active-arm (n=40) used the MTX information booklet for the patients' education and the control-arm (n=38) did not. Patients' interviews were conducted over a 6-month period using an MTX-questionnaire. RESULTS: The entire active-arm patients (100%) were taking folic-acid and 32 (80%) knew the reason why they were taking folic-acid vs. [30 (79%) and 10 (26%) in the control-arm]. In the active-arm 35 (88%) knew the reason for their monthly blood tests vs. 18 (47%) in the control-arm. The entire active-arm was aware of the need for contraception use and MTX-side effects vs. 23 (60%) and 15 (40%) in the control-arm respectively. CONCLUSIONS: The use of the MTX information booklet in our cohort improved their understanding of the treatment.
19652507 Erythrocyte methotrexate-polyglutamate assay using fluorescence polarization immunoassay t 2009 Aug Methotrexate (MTX), i.e., MTX-polygluatmate 1 (MTX-PG(1)), exerts its antirheumatic effects mainly by < or = 6 (MTX-PG(2-7)) via folypolyglutamyl synthase in cells. The authors developed a new method using fluorescence polarization immunoassay to determine MTX-PG(1-7) concentrations in erythrocytes (RBC). MTX-PG(2-7) in RBC of rheumatoid arthritis (RA) patients receiving MTX was converted to MTX in the presence of plasma gamma-glutamyl hydrolase and mercaptoethanol at 37 degrees C. The MTX in RBC was extracted in a perchloric acid deproteinization step then on a solid-phase extraction column. The concentration of MTX was measured by TDX analyzer. The mean MTX recovery rate was 76.1% (n=8). The intraday and interday coefficients of variation were <11.3% (n=8) and <12.4% (n=3), respectively, at low and high concentrations (30-300 nmol/l). The calibration curve was linear over the range 30-300 nmol/l. The total concentration of MTX-PGs (mean+/-S.D.) in RBC obtained from 95 Japanese RA patient blood samples was 97.3+/-8.1 nmol/l for the MTX dose of 0.13+/-0.05 mg/week/kg. This newly developed method for the quantification of MTX-PGs in RBC is sensitive and accurate and can be applied for routine monitoring of MTX therapy in RA patients.
20617749 [The goal for the treatment of rheumatoid arthritis should be remission]. 2010 Early diagnosis is the cornerstone for a successful treatment of rheumatoid arthritis. The Finnish way is to start early using the combination of three disease modifying drugs (methotrexate, sulphasalazine, hydroxychloroquine) and a low dose of glucocorticoid (FIN-RACo strategy) aiming at remission. A tight control of disease activity and flexible adjustment of drug therapy are needed using local joint injections, as well. In severe disease with insufficient treatment response, the new biologicals are indicated before marked joint damages occur.
19549290 Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open- 2009 INTRODUCTION: Since current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA. METHODS: This was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12. RESULTS: Improvement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency and tolerability trends. CONCLUSIONS: Treatment with masitinib improved DMARD-refractory active RA. Following an initial high incidence of mostly mild to moderate side effects during the first 12 weeks of treatment, masitinib appears to be generally well tolerated. This, together with evidence of a sustainable efficacy response, suggests that masitinib is suitable for long-term treatment regimens. Since this was the first study of masitinib in a nononcologic pathology, the relatively high patient withdrawal rate observed can be partly attributed to a highly cautious response to adverse events. There is sufficient compelling evidence to warrant further placebo-controlled investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00831922.
20416859 [Lipid profile and cardiovascular risk in patients with rheumatoid arthritis: Effect of th 2010 Sep The increased mortality in patients with rheumathoid arthritis (RA) is mainly due to high incidence of cardiovascular (CV) disease. CV morbidity and mortality in RA can be explained by several mechanisms: (1) chronic inflammation, (2) enhanced prevalence of traditional CV risk factors including atherogenic dyslipoproteinemia, (3) a lower use of evidence-based therapy such as statins and (4) chronic treatment for RA such as glucocorticoids. It is difficult to distinguish between the role of pharmacological treatment per se and the severity or duration of the disease since these two parameters are closely interrelated. RA likely influences lipoprotein metabolism leading to quantitative and qualitative alteration of low-density lipoproteins (LDL) and of high-density lipoproteins. Glucocorticoids alter carbohydrate and lipid metabolism. However, by reducing the inflammation level, the net effect on lipid parameters and on the CV risk may be favorable. Data from open follow-up studies would suggest that methotrexate use is associated with a beneficial effect on lipid parameters and with a reduction in the incidence of CV disease. Anti-TNF agents increase LDL-cholesterol in some but not all studies; however the use of anti-TNF agents likely reduce CV risk in patients with RA. The influence of recently developed compounds, anti-CD20, CTLA-4 Ig or anti-IL6 is not well documented. Anti-IL6 seem to increase total and LDL-cholesterol; however these changes are associated with an improvement in the TC/HDL-C ratio.
20921970 A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in e 2012 Apr Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.
20074482 The economic burden of biological therapy in rheumatoid arthritis in clinical practice: co 2009 Oct Rheumatoid arthritis (RA), with a prevalence of 0.46%, is found in about 272,004 patients in Italy. The socioeconomic cost of rheumatoid arthritis in Italy in 2002 has been estimated at Euro 1,600 million. Cost-effectiveness evaluations have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. Many cost-effective studies have been based on the variation of Health Assessment Questionnaire (HAQ) in clinical trials. The objective of this study is to perform a cost-effective analysis of 86 patients with rheumatoid arthritis in therapy with adalimumab 40 mg every other week and etanercept 50 mg/week for two years in a population of patients observed in clinical practice. The group of patients in therapy with adalimumab had also taken methotrexate, mean dose 12.4+/-2.5 mg/week (22 patients) or leflunomide 20 mg/day (16 patients). The group of patients in therapy with etanercept had also taken methotrexate, mean dose 11.7+/-2.6 mg/week (24 patients) or leflunomide 20 mg/day (24 patients). Incremental costs and QALYs (quality adjusted life years) gains are calculated compared with baseline, assuming that without biologic treatment patients would remain at the baseline level through the year. Conversion HAQ scores to utility were based on the Bansback algorithm. The results after two years showed: in the group methotrexate+adalimumab the QALY gained was 0.62+/-0.15 with a treatment cost of Euro 26,517.62 and a QALY/cost of Euro 42,521.13. In the group methotrexate + etanercept the QALY gained was 0.64+/-0.26 with a treatment cost of Euro 25,020.96 and a QALY/cost of Euro 39,171.76. The result of using etanercept in association with methotrexate is cost-effectiveness with a QALY gained under the acceptable threshold of Euro 50,000. These are important data for discussion from an economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.