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ID PMID Title PublicationDate abstract
20979564 The efficacy and safety of interleukin-1-receptor antagonist anakinra in the treatment of 2010 Dec IMPORTANCE OF THE FIELD: Systemic juvenile idiopathic arthritis (sJIA) is a debilitating childhood disease presenting with fever, rash and arthritis. Current therapy consisting mainly of corticosteroids, NSAIDs and methotrexate, can be inefficient and is often accompanied by many serious adverse events. Although an IL-1 receptor antagonist (anakinra) seems to be very efficient in case series, it is not registered for use in sJIA. Pediatric rheumatologists all over the world are having a hard time to convince insurance companies to approve off-label use of this drug for their sJIA patients. AREAS COVERED IN THIS REVIEW: Using the MeSH terms 'Arthritis Juvenile Rheumatoid' and 'Interleukin 1 Receptor Antagonist Protein', we searched MEDLINE, EMBASE and reference lists of selected articles. This review is largely based on manuscripts from 2005 to 2010 and abstracts presented at the major (pediatric) rheumatology congresses. WHAT THE READER WILL GAIN: This review summarizes the data of 140 children with sJIA treated with anakinra and enables an understanding in the benefit-risk profile of anakinra in sJIA patients. TAKE HOME MESSAGE: Anakinra has shown to be a very efficient and quick acting medicine in reducing symptoms even in therapy-resistant sJIA patients with typically poor outcomes.
20008919 Peripheral blood expression profiles of bone morphogenetic proteins, tumor necrosis factor 2010 Feb OBJECTIVE: To assess whether different forms of arthritis and disease activity could be distinguished by peripheral blood expression profiles of bone-regulatory factors including tumor necrosis factor (TNF)-superfamily [TNF-related apoptosis-inducing ligand (TRAIL), the Fas ligand (FasL), and the ligand for herpesvirus entry mediator (LIGHT)] and bone morphogenetic protein (BMP)-family members (BMP-2, BMP-4, BMP-6) as well as osteoblast differentiation gene Runx2. METHODS: Blood cells from healthy controls (n = 25) and patients at different disease stages with rheumatoid arthritis (RA; n = 49), osteoarthritis (OA; n = 17), or spondyloarthritis, including ankylosing spondylitis (AS; n = 27) or psoriatic arthritis (PsA; n = 23), were processed for quantitative polymerase chain reaction. Gene expression was assessed in comparison with control samples, correlated with clinical data of different forms of arthritis, and analyzed for discriminative efficacy between groups by receiver-operation characteristic (ROC) curves. Results were confirmed on diagnostic RA (n = 5) and AS (n = 8) samples. RESULTS: BMP-4, BMP-6, and Runx2 expressions were significantly decreased in patients with RA and OA versus controls. Patients with RA also had decreased FasL and LIGHT expression, while patients with AS had increased Runx2 expression. Negative correlation with disease activity was found for BMP-4, FasL, and Runx2 in RA and for Runx2 in PsA, while positive correlation was found for BMP-4 in PsA. Gene expression was higher in the therapy-resistant form of AS (for BMP-4, LIGHT, and Runx2) and in methotrexate-treated patients in RA (for BMP-2 and LIGHT). ROC curve analysis confirmed discrimination between groups, particularly decreased LIGHT and Runx2 for RA and increased Runx2 for AS. CONCLUSION: Our study identified BMP and Runx2 as possible biomarkers of bone metabolism in several forms of arthritis, while lower FasL and LIGHT were associated with RA. Correlation between gene expression and disease activity may be clinically useful in assessing therapeutic effectiveness and disease monitoring.
21044446 Use of methotrexate in patients with ankylosing spondylitis. 2010 Sep The disease modifying antirheumatic drug (DMARD) methotrexate (MTX) is widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). In ankylosing spondylitis (AS), the use of MTX is not recommended for the axial manifestations and may have some efficacy in the peripheral involvement. For this disease there is a lack of clinical trials, and most of the trials did not show efficacy on the axial symptoms of the disease. Furthermore, there is no evidence that MTX increases the effects or prevents the side effects of TNF-blockers if given in combination. In this paper the available data of MTX in AS will be discussed.
19190623 Certolizumab pegol--what role does this new TNF inhibitor have in the treatment of RA? 2009 Mar The efficacy and safety of a new tumor necrosis factor inhibitor, certolizumab pegol, in active rheumatoid arthritis has now been assessed in three phase III, multicenter, randomized, double-blind, placebo-controlled clinical trials. This commentary focuses on the paper by Keystone et al., in which patients were followed for the longest duration. This study, which compared two doses of subcutaneous certolizumab pegol with placebo in patients with active RA receiving methotrexate, showed no advantage of 400 mg over 200 mg certolizumab pegol over 52 weeks, after induction with 400 mg. The nature of the patients enrolled in this study, trial design and possible safety issues are discussed, as is whether this trial can teach us anything about tumor necrosis factor inhibitors in general. On the basis of the results from this study, certolizumab pegol does not represent a major addition to our armamentarium, but because of the slightly different mechanism of action and structure of this drug, and the apparently acceptable therapeutic effects over one year, it is, nevertheless, welcome.
21794580 [A comparison of leflunomide and subcutaneous methotrexate in the treatment of rheumatoid 2009 Mar OBJECTIVE: To compare, in the Spanish setting, two drugs for adults with rheumatoid artritis (RA): leflunomide and subcutaneous methotrexate (SC). The high price of methotrexate SC compared with traditional presentations of methotrexate justifies conducting an economic evaluation comparing it with leflunomide. METHODS: The analysis considered the annual costs of the drugs and their effectiveness, measured with a Number Needed to Treat (NNT) approach, considering both the ACR20 and ACR50 criteria for effectiveness. Data about efficacy and dosage were derived from the clinical trial US310, a randomized, doble-blinded controlled trial, which compared efficacy and safety of leflunomide (20mg/daily) vs placebo vs methotrexate (7.5-15mg/weekly) in 482 patients with active RA. Data about use of medical resources for drug monitoring (visits to rheumatologists and diagnostic procedures) were derived from the manufacturers' summary of product characteristics. Direct costs (drugs and monitoring) were obtained from two Spanish databases. The analysis has been performed under the Spanish National Health System perspective. RESULTS: Using the ACR20 criteria, the NNT with leflunomide and methotrexate are 4 (95% CI, 2.56-7.71) and 5 (95% CI, 3.03-14.3) respectively. Using the ACR50 criteria, NNT are 4 (95% CI, 2.72-6.54) and 7 (95% CI, 4.03-19.3). In the case of leflunomide, annual treatment costs per patient-year equals 1,793.30€; in the case of methotrexate total treatment costs amounts to 2,149.20€. CONCLUSIONS: Combining these results the cost of a controlled patient according to ACR20 would amount 7,173€ for leflunomide and 10,746€ for methotrexate SC. Results considering ACR50 are 7,173€ and 15,044€ for leflunomide and methotrexate respectively.
21437059 Long-term use of adalimumab in the treatment of moderate to severe plaque psoriasis: a rev 2010 Apr 19 Psoriasis is a chronic T-cell-mediated inflammatory disease that primarily affects the skin and joints. Patients with moderate to severe psoriasis constitute about 30% of the psoriasis population. Treatment of this group is challenging due to the long-term side effects, toxicities and inconvenience of conventional treatments such as phototherapy, methotrexate and cyclosporine. However, recent advances in our understanding of the pathogenesis of psoriasis have led to the popular use of biologics, which offer a safer, more convenient and effective targeted therapy. Adalimumab was originally approved for treating rheumatoid arthritis. Currently, adalimumab is also approved for treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy or when other systemic therapies are medically less appropriate. Since the onset of the use of biologics, there have been concerns over safety and efficacy when used as long-term therapy. This paper reviews all publications, posters and abstracts reporting original data on the efficacy and/or safety of adalimumab in patients treated for chronic plaque psoriasis for more than 1 year.
20001596 Indirect cost-effectiveness analyses of abatacept and rituximab in patients with moderate- 2010 Mar OBJECTIVE: To estimate the incremental cost per quality-adjusted life-years (QALYs) for abatacept and rituximab, in combination with methotrexate, relative to methotrexate alone in patients with active rheumatoid arthritis (RA). METHODS: A patient-level simulation model was used to depict the progression of functional disability over the lifetimes of women aged 55-64 years with active RA and inadequate response to a tumor necrosis factor (TNF)-alpha antagonist therapy. Future health-state utilities and medical care costs were based on projected values of the Health Assessment Questionnaire Disability Index (HAQ-DI). Patients were assumed to receive abatacept or rituximab in combination with methotrexate until death or therapy discontinuation due to lack of efficacy or adverse events. HAQ-DI improvement at month 6, after adjustments for control drug (methotrexate) response, was derived from two clinical trials. Costs of medical care and biologic drugs, discounted at 3% annually, were from the perspective of a US third-party payer and expressed in 2007 US dollars. RESULTS: Relative to methotrexate alone, abatacept/methotrexate and rituximab/methotrexate therapies were estimated to yield an average of 1.25 and 1.10 additional QALYs per patient, at mean incremental costs of $58,989 and $60,380, respectively. The incremental cost-utility ratio relative to methotrexate was $47,191 (95% CI $44,810-49,920) per QALY gained for abatacept/methotrexate and $54,891 (95% CI $52,274-58,073) per QALY gained for rituximab/methotrexate. At an acceptability threshold of $50,000 per QALY, the probability of cost effectiveness was 90% for abatacept and 0.0% for rituximab. CONCLUSION: Abatacept was estimated to be more cost effective than rituximab for use in RA from a US third-party payer perspective. However, head-to-head clinical trials and long-term observational data are needed to confirm these findings.
19344980 Treatments for psoriasis and the risk of malignancy. 2009 Jun BACKGROUND: There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy. OBJECTIVE: Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab. RESULTS: PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies-MTX, CsA, and MMF-may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor-alpha inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies. LIMITATIONS: The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor. CONCLUSION: Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.
19228423 Point mutation of tyrosine 759 of the IL-6 family cytokine receptor, gp130, augments colla 2009 Feb 19 BACKGROUND: Knock-in mice (gp130F759) with a Y759F point mutation in gp130, a signal transducing receptor subunit shared by members of the IL-6 cytokine family, show sustained activation of STAT3, enhanced acute-phase or immune responses, and autoimmune arthritis. We conducted a detailed analysis of collagen-induced arthritis (CIA) in gp130F759 with a DBA/1J background (D/J.gp130F759). METHODS: We backcrossed gp130F759 to C57BL/6 and DBA/1J, and compared the pathologic changes, including occurrence of arthritis, in the two distinct genetic backgrounds. We analyzed CIA in D/J.gp130F759 and investigated the effects of methotrexate (MTX) on CIA. RESULTS: C57BL/6 background gp130F759 mice, but not D/J.gp130F759, spontaneously developed polyarthritis and glomerulonephritis. On the other hand, keratitis of the eyes only developed in D/J.gp130F759, indicating the influence of genetic background on disease development in gp130F759 mice. Resistance of the DBA/1J background against spontaneous arthritis urged us to examine CIA in D/J.gp130F759. CIA in D/J.gp130F759 was more severe, with greater bone destruction, than the control mice. After collagen immunization, splenomegaly and serum levels of rheumatoid factor and anti-DNA antibody were augmented in D/J.gp130F759. Bio-Plex analysis of serum cytokines revealed increased IL-12p40 and PDGF-BB before immunization, and increased levels of IFN-gamma, IL-17, TNF-alpha, IL-9, and MIP-1beta 8 days after the booster dose. IL-6 and PDGF-BB in D/J.gp130F759 showed distinct kinetics from the other cytokines; higher levels were observed after arthritis development. MTX partially attenuated the development of arthritis and inhibited bone destruction in D/J.gp130F759, with reduction of anti-type II collagen antibody levels, suggesting that MTX mainly affects antigen-specific immune responses in CIA. CONCLUSION: The Tyr-759 point mutation of the IL-6 family cytokine receptor subunit, gp130, caused autoimmune disease, and this was also influenced by the genetic background. CIA in D/J.gp130F759 is useful for evaluating drugs in a relatively short period because sustained activation of STAT3 may enhance the disease symptoms.
20426959 [Reiter's syndrome in children: a clinical analysis of 22 cases]. 2010 Mar OBJECTIVE: To study the clinical features of Reiter's syndrome (RS) in children. METHOD: Twenty-two patients with RS were referred to our department between August 2002 and September 2008. Their clinical features were analyzed retrospectively. RESULT: Of the 22 patients, 19 were male, only 3 were female. Age ranged from 4 to 14 years, and the average was 10.7 years, most patients (20/22) were older than eight. Among their relatives, 2 had ankylosing spondylitis, 4 had undifferentiated spondyloarthropathy or presented with a history of inflammatory low back pain, and 2 had psoriasis. The season of onset of all patients was summer months from June to September every year. Ten had a history of diarrhea within 1 month preceding the symptoms of arthritis. Twenty-one had fever at the onset. Conjunctivitis occurred in 20 patients, only one was complicated with uveitis. Urethral symptoms occurred in 12 patients, and another 3 patients had abnormal results of urine analysis only. Synovitis occurred in all cases, most of whom had oligoarthritis, predominantly affecting large joints of the lower limbs in an asymmetric pattern with enthesitis occurred in 9. Balanitis circinata was common in male patients (10/19). Elevated inflammatory indicators such as white blood cell, neutrophil, platelet, erythrocyte sedimentation rate, C-reactive protein, immunoglobulins and serum complement C3 were common during the acute illness. All of the 22 cases were negative for rheumatoid factor and 16 (72.7%) were HLA-B27 positive. Nonsteroidal anti-inflammatory drugs and sulfasalazine were the mainstay of treatment. Cyclophosphamide was used in 14 patients (total doses 0.6 - 2.0 g), in 4 cases methotrexate was added. Corticosteroids were added in 4 patients and cyclosporine was given to the patient complicated with uveitis. Most patients achieved full remission within 6 months. CONCLUSION: RS is common in children with clinical features different from those in adults and a relatively good prognosis.
19749141 Inflammatory bowel disease and lymphoproliferative disorders: the dust is starting to sett 2009 Oct The risk of lymphoproliferative disorders (LDs) has become a major concern for clinicians managing patients with inflammatory bowel disease (IBD). Yet it is difficult to distinguish the possible responsibility of immunosuppressive therapy from the background risk due to the inflammatory disorder itself. LDs are clonal B or T cell proliferation showing considerable heterogeneity and the incidence has increased since the 1970s. The strongest and best-established risk factors for LDs are primary and acquired immunodeficiency (HIV, immunosuppressant), notably via defective immune surveillance of Epstein-Barr virus. In many auto-immune diseases (eg, Sjögren's syndrome), inflammatory diseases (eg, rheumatoid arthritis) or chronic suppuration (chronic pyothorax), the risk of LD is increased. In IBD patients, in general, the risk of LD seems to be similar to or very slightly higher than in the general population. The role of immunosuppressants in lymphomagenesis is difficult to individualise because other factors potentially involved are inter-linked. Concordant data suggest that thiopurine therapy is associated with a moderately increased risk of LD. Data regarding methotrexate are scarce and come from diseases other than IBD but the risk seems low. Data regarding risk of LD in IBD patients receiving anti-tumour necrosis factor alpha (TNFalpha) agents are insufficient at this time, mainly because most of the patients are co-treated with thiopurines. The recently individualised risks of hepatosplenic T cell lymphoma and fatal post-mononucleosis LD, in young male patients with IBD who are co-treated with anti-TNFalpha and thiopurines, and EBV-seronegative IBD males, respectively, are probably low but remain to be better quantified.
19569279 [Enteritis and cystitis - a cause of abdominal pain in lupus]. 2009 Apr We present a case of a 28-year-old black female patient with a previous diagnosis of overlapping syndrome of lupus and rheumatoid arthritis, treated with corticosteroids and methotrexate, who was admitted to our department due to abdominal pain with vomits and diarrhea for 15 days. On complementary evaluation elevated C-reactive protein and erythrocyte sedimentation rate, lactate dehydrogenase and amylase levels were detected, C3 was reduced, blood, faeces, peritoneal fluid and urine cultures were negative; abdominal computerized tomography disclosed jejunal thickening with parietal edema, bilateral ureterohydronephrosis and bladder parietal thickening; on endoscopy with biopsy there was chronic pangastritis and duodenitis; cystoscopy with biopsy showed chronic cystitis. Those aspects suggested lupus enteritis and cystitis which appear rarely associated and have poor prognosis. This patient was treated with high dose corticosteroids followed by azathioprine and prednisolone, with clinical and imaging improvement.
19110071 Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of 2009 Feb 19 Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report that FA and FNA ameliorate the germ cell toxicity of MTX in mice.
21044451 Use of methotrexate in patients with systemic lupus erythematosus and primary Sjögren's s 2010 Sep While there is still no convincing evidence that methotrexate is of benefit in primary Sjögren's syndrome, the SLE evidence on this rheumatology anchor drug is substantial. In fact, there are randomised controlled trials showing the benefit for methotrexate on overall SLE activity, reduction in glucocorticoid doses, and effects on lupus arthritis and lupus skin manifestations. In addition, methotrexate may be helpful in vasculitis, haematological manifestations, and perhaps kidney disease. Intrathecal methotrexate was successfully used in neuropsychiatric SLE. Taken together, using methotrexate in SLE is not only a common approach, but, at least in part, supported by evidence from clinical trials.
19693642 Drug treatment-induced downregulation of antiphospholipid antibodies in PAPS. 2009 Nov Although low-dose methotrexate (MTX) has been used to treat several autoimmune diseases like lupus erythematosus, rheumatoid arthritis, etc., it has not yet been used to treat patients with primary antiphospholipid syndrome (PAPS). Parallel to clinical follow-up of female patient with a severe form of PAPS, antiphospholipid antibodies (aPL), blood coagulation, and hematological parameters in the peripheral blood have been monitored. MTX improved ulcers, livedo reticularis, decreased aPL titers, increased platelet counts, and improved blood coagulation parameters (e.g., factor VIII) and was well tolerated. Low-dose MTX was safe and effective in the presented case with PAPS. The clinical benefit may be due to the downregulation of increased aPL titers and amelioration of disturbed coagulation parameters.
19630828 Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the card 2009 Jul While inflammation is a crucial component of atherothrombosis and patients with elevated inflammatory biomarkers such as high sensitivity C-reactive protein (hsCRP) are at increased vascular risk, it remains unknown whether inhibition of inflammation per se will lower vascular event rates. The recently completed JUPITER (N Engl J Med 2008, 359, 2195) trial demonstrates that statins reduce myocardial infarction, stroke, and all-cause mortality among healthy individuals with low cholesterol and elevated hsCRP. However, a direct test of the inflammatory hypothesis of atherothrombosis requires an agent that inhibits inflammation without impacting other components of the atherothrombotic process, and has an acceptable safety profile for a trial setting. On this basis, the cardiovascular inflammation reduction trial (CIRT) proposes to allocate 7000 stable coronary artery disease patients with persistent elevations of hsCRP to placebo or very-low-dose-methotrexate (VLDM, 10 mg weekly), a proven anti-inflammatory regimen that reduces TNFalpha, IL-6, and CRP levels and is in wide use among rheumatoid arthritis patients. If successful, CIRT would both confirm the inflammatory hypothesis of atherothrombosis and open novel approaches to the treatment and prevention of cardiovascular disorders.
20737185 Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with 2011 Feb A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.
18292102 Can clinical factors at presentation be used to predict outcome of treatment with methotre 2009 Jan PURPOSE: Methotrexate (MTX) is the first choice conventional disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis. It is not universally effective, however; although to date it is not possible to predict with any accuracy which patients will respond to treatment. The aim of this analysis was to examine whether clinical and genetic variables could be used to predict response to MTX. METHODS: Patients recruited to the Norfolk Arthritis Register (NOAR), a primary care based inception cohort of patients with inflammatory polyarthritis, were eligible for this analysis if they were commenced on MTX as their first DMARD within 3 months of their baseline visit and had at least 2 years of follow-up data. Outcome on MTX was defined as: (1) stopped for adverse events; (2) stopped for inefficacy or second DMARD added; (3) stopped for other reasons; or (4) remained on MTX monotherapy. Multiple logistic regression was used to establish which variables (including demographics, disease activity and Health Assessment Questionnaire score) predicted stopping monotherapy for inefficacy or adverse event (with those remaining on treatment taken as the referent category). The area under the Receiver Operating Characteristic curves (AUC ROC), were used to determine how accurate the model was at predicting outcome. RESULTS: 309 patients were included in this analysis. At 1 year (2 years), 34 (46) patients had stopped for adverse events and 25 (49) had either stopped monotherapy for inefficacy or had a second DMARD added. 231 (188) patients remained on MTX monotherapy. The strongest predictor of inefficacy at both time points was shared epitope positivity: odds ratios (OR) 5.8 (95% confidence intervals (CI) 1.3 to 25.6) at 1 year, OR 3.0 (95% CI 1.3 to 7.3) at 2 years. High Health Assessment Questionnaire score (OR 1.84 95% CI 1.12 to 3.01) and female gender (OR 2.2, 95% CI 0.92 to 5.28) were associated with adverse events on MTX at 1 year. However, even the most optimal combinations of the factors analysed were only weakly predictive of treatment outcome: AUC ROC for adverse events 0.68 (95% CI 0.58 to 0.78) and for inefficacy AUC ROC 0.71 (95% CI 0.6 to 0.81). CONCLUSIONS: Within this cohort, routine clinical and laboratory factors were poor at predicting outcome of treatment with MTX. Given the major therapeutic advantage to be derived from accurate prediction of treatment outcome, further studies will need to investigate novel biological and other markers.
20658239 Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthriti 2012 Jan Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.
20411808 [Case of toxoplasma encephalopathy with specific MRI findings, diagnosed by IgG avidity in 2010 Apr We report a 60-year-old woman with toxoplasma encephalopathy. She was being treated with prednisolone and methotrexate for rheumatoid arthritis that was diagnosed at the age of 40. In a preoperative examination of her left fifth finger ganglion, pericardial effusions, cardiomegaly, and a right atrial mass were detected. In addition, brain MRI showed nodular shadows in the right thalamus, bilateral globus pallidus, and left dentate nucleus of the cerebellum. T1 and T2 weighted images showed high intensities within those shadows; however, a T1 gadolinium enhancement image showed no contrast enhancement in the lesions. There were no positive neurological findings. Examination of the cerebrospinal fluid and cultivation tests showed nothing particular. The right atrial mass was subsequently diagnosed as malignant lymphoma and treated with radiation therapy. Toxoplasma gondii antibody titers were increased in both serum and cerebrospinal fluid. Based on IgG avidity index and nested PCR, we diagnosed toxoplasma encephalopathy with chronic T. gondii infection. The T. gondii gene product was also detected in cerebrospinal fluid by nested PCR. We consider that IgG avidity index and nested PCR were useful for the diagnosis of toxoplasma encephalopathy.