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ID PMID Title PublicationDate abstract
18675138 [What's new in medicine in 2007?]. 2007 Dec What's new in medicine in 2007? Find out what has changed in medicine in 2007 in the field of inflammatory and autoimmune diseases. The year has been productive with many fundamental advances. 2007 was the year of genetics in autoimmune diseases (rheumatoid arthritis, lupus, scleroderma, vascularities, etc.), coming notably from work by the WTCCC. The comprehension of inflammatory diseases is based on increasingly detailed knowledge of epigenetic regulation and posttranscriptional mechanisms. The small RNA play a fundamental role and potentially offer many therapeutic applications.Sex and stress play a role in the appearance of inflammatory diseases. The mechanisms are progressively being better understood.More and more illnesses have autoimmune mechanisms, such as emphysema in the ex-smoker or pustulosis palmaris et plantaris. The revolution in biological therapies is continuing to grow. Medications that modulate innate immunity are being evaluated in inflammatory, allergic, and neoplastic diseases. Other, sometimes surprising options such as arsenic are now possible.
18240241 The HLA-DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in A 2008 Feb OBJECTIVE: To determine whether shared epitope (SE)-containing HLA-DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population. METHODS: In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry. RESULTS: The frequency of SE-containing HLA-DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA-DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody-positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody-negative RA (P = 0.01, by chi-square test). CONCLUSION: HLA-DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which approximately 50-70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.
16431346 BiP regulates autoimmune inflammation and tissue damage. 2006 Feb The endoplasmic reticulum chaperone BiP, in addition to its many important intracellular functions, has anti-inflammatory and immunomodulatory properties when present in the extracellular environment by the stimulation of an anti-inflammatory gene programme from human monocytes and by the development of T-cells that secrete regulatory cytokines such as interleukin-10 and interleukin-4. It can both prevent as well as treat ongoing collagen-induced arthritis. It is, therefore, a potential new biologic therapy for rheumatoid arthritis.
16900557 Using mixed treatment comparisons and meta-regression to perform indirect comparisons to e 2007 Mar 15 Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of the same treatment for a disease being tested in a number of studies, a number of different interventions are considered. Meta-regression is also a generalization of meta-analysis where an attempt is made to explain the heterogeneity between the treatment effects in the studies by regressing on study-level covariables. Our focus is where there are several different treatments considered in a number of randomized controlled trials in a specific disease, the same treatment can be applied in several arms within a study, and where differences in efficacy can be explained by differences in the study settings. We develop methods for simultaneously comparing several treatments and adjusting for study-level covariables by combining ideas from MTC and meta-regression. We use a case study from rheumatoid arthritis. We identified relevant trials of biologic verses standard therapy or placebo and extracted the doses, comparators and patient baseline characteristics. Efficacy is measured using the log odds ratio of achieving six-month ACR50 responder status. A random-effects meta-regression model is fitted which adjusts the log odds ratio for study-level prognostic factors. A different random-effect distribution on the log odds ratios is allowed for each different treatment. The odds ratio is found as a function of the prognostic factors for each treatment. The apparent differences in the randomized trials between tumour necrosis factor alpha (TNF- alpha) antagonists are explained by differences in prognostic factors and the analysis suggests that these drugs as a class are not different from each other.
16257399 Review: Collagen markers in early arthritic diseases. 2006 Mar In arthritic diseases e.g. osteoarthritis (OA) and rheumatoid arthritis (RA), the stability of the collagen type II (CII) fibers, a major component of articular cartilage, is compromised with extensive proteolytic breakdown leading to cartilage erosion and joint deterioration. A clinical need for molecular markers that give instantaneous measure of rate of joint deterioration has developed, as other measurements e.g. arthroscopy, and joint space narrowing are insensitive to small changes in disease status over short periods of time. Owing to its exclusive presence in cartilaginous tissues, markers of CII synthesis and degradation have been extensively studied. Assays that measure these markers in biological fluids e.g. synovial fluid (SF), serum, and urine have been developed and applied to detect early disease onset, monitor disease progression, and response to anti-arthritic drugs. CII synthesis markers include the procollagen type II C-propeptide (PIICP) and the procollagen type IIA N-propeptide (PIIANP). CII degradation markers include CII C-telopeptide (CII-X), CII neoepitope (TIINE), helix II, C2C, CNBr 9.7, Coll 2-1, and Coll 2-1 NO(2). Most of these markers differentiate between early stages of OA, RA and reference controls. The best correlations with structural changes occur when measurements are made in SF while serum measurement frequently did not correlate with structural changes. Although the selection of an optimal marker or a set of markers is still problematic, few markers are of considerable utility in early detection and monitoring of arthritic diseases. The current challenge is to improve the discriminatory power of these markers so they can be used to guide therapeutic decisions.
17517474 One day at a time: The impact of daily satisfaction with spouse responses on pain, negativ 2007 Sep The majority of research on pain catastrophizing has focused on its negative consequences for adjustment to chronic pain, with few investigations of factors that influence catastrophizing or its detrimental effects. Using a daily process methodology, the current study examined, first, the extent to which a supportive social environment plays a role in reduced catastrophizing, and second, the extent to which support might protect against the detrimental effects of catastrophizing on well-being. Sixty-nine married individuals with rheumatoid arthritis took part in an initial background interview, followed by twice daily telephone interviews (regarding pain intensity, negative affect, catastrophizing and satisfaction with spouse responses) for 1 week. Multi-level modeling indicated several pathways through which satisfaction with spouse responses disrupts the vicious cycle of pain, negative affect and catastrophizing. Consistent with past research, catastrophizing was associated with increases in pain and negative affect. However, when individuals reported increases in satisfaction with spouse responses they were less likely to experience increases in negative affect due to catastrophizing. Satisfaction with spouse responses also reduced the likelihood of feeling overwhelmed and helpless in dealing with daily pain. The relationship between pain and catastrophizing was attenuated in the context of increases in satisfaction with spouse responses. Negative affect was associated with increases in catastrophizing, but only when individuals reported decreases in satisfaction with spouse responses. Overall, findings were consistent with a model in which satisfaction with spouse responses serves as a coping resource, and suggests the importance of involving close others in treatments to reduce pain and catastrophizing.
17073674 Dissecting the genetic basis of rheumatoid arthritis in mouse models. 2006 Rheumatoid Arthritis, RA, is a common polygenic multi-factorial chronic inflammatory disorder that involves complex interactions between genetic and environmental factors. Despite major advances, the aetiology of the disease is still not completely understood. In this post-genome era, the sequencing of the human and some murine genomes as well as advances in global screening technologies offer an opportunity to accelerate the search for new pathological pathways and to identify new therapeutic targets. Animal models of RA offer an opportunity to dissect the genetic basis of disease in a simplified genome and controlled environment with the aim of identifying new pathological pathways and thus new therapeutic targets. Linkage analysis in the mouse model has identified more than 60 Loci, controlling disease phenotypes, immune response and cytokines. This indicates that gene variations among inbred mice strains affect the disease and that those polymorphic genes could be potential therapeutic targets. However, progress in identification of susceptibility genes in mouse models is slow. The progress is hampered by the complexity of disease as well as the traditional genetic dissection strategies. In this post-genome era, the sequencing of the human and some murine genomes as well as advances in global screening technologies offer an opportunity to accelerate the progress.
18521991 Celecoxib: still around, unfortunately. 2008 Apr In France, the Transparency Committee has now given celecoxib their lowest rating for "medical benefits", i.e. no medical advantage. So when will the regulatory agencies finally decide to withdraw it from the market?
16409309 Access to tumour necrosis factor inhibitors for rheumatoid arthritis treatment under the A 2006 Jan BACKGROUND: Access to tumour necrosis factor inhibitors (TNFI) for the treatment of rheumatoid arthritis under the Australian Pharmaceutical Benefits Scheme (PBS) is governed by a set of arrangements, operational from August 2003. Patients must meet strict criteria for both starting and continuing TNFI. Examination of utilization data is important for assessing the broader implications of arrangements for access to expensive pharmaceuticals under schemes such as the PBS. AIM: To examine the uptake of TNFI over the first year of subsidized availability of etanercept under the PBS, and to compare these data to the predicted utilization and expenditure. METHODS: Collection and analysis of prescription and expenditure data for the three listed TNFI: etanercept, infliximab and adalimumab processed under the PBS for the period August 2003 to July 2004. RESULTS: A total of 8,053 prescriptions for TNFI was reimbursed at a total cost of 15.2 m Australian dollars. The total PBS expenditure on etanercept was just over 14 m Australian dollars, 14% of the predicted annual expenditure. The relative per capita uptake of etanercept was highest in the Australian Capital Territory and lowest in the Northern Territory. More than 50% of prescriptions for etanercept were for concessional patients (7.3 m Australian dollars). CONCLUSION: Prescription rates and expenditure on etanercept were substantially below those forecast over the first year. There are opportunities to adjust the PBS restrictions for subsidized access to TNFI to benefit more patients.
17610723 An audit of influenza and pneumococcal vaccination in rheumatology outpatients. 2007 Jul 4 BACKGROUND: Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. METHOD: We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. RESULTS: Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p < 0.001) or streptococcus pneumoniae (28% vs 64%, p = 0.001). The presence of additional risk factors was confirmed as significant in determining vaccination status by logistic regression for both influenza (OR 10.89, p < 0.001) and streptococcus pneumoniae (OR 4.55, p = 0.002). The diagnosis of rheumatoid arthritis was also found to be a significant factor for pneumococcal vaccination (OR 5.1, p = 0.002). There was a negative trend suggesting that patients on major immunosuppressants are less likely to be immunised against pneumococcal antigen (OR 0.35, p = 0.067). CONCLUSION: Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.
16343797 Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: a ca 2006 A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20+, and a portion of them was CD30+. The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein-Barr virus-encoded small RNA-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.
17195208 Dissecting the heterogeneity of rheumatoid arthritis through linkage analysis of quantitat 2007 Jan OBJECTIVE: To dissect the heterogeneity of rheumatoid arthritis (RA) through linkage analysis of quantitative traits, specifically, IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibody titers. METHODS: Subjects, 1,002 RA patients from 491 multiplex families recruited by the North American RA Consortium, were typed for 379 microsatellite markers. Anti-CCP titers were determined based on a second-generation enzyme-linked immunosorbent assay, and IgM-RF levels were quantified by immunonephelometry. We used the Merlin statistical package to perform nonparametric quantitative trait linkage analysis. RESULTS: For each of the quantitative traits, evidence of linkage, with logarithm of odds (LOD) scores of >1.0, was found in 9 regions. For both traits, the strongest evidence of linkage was for marker D6S1629 on chromosome 6p (LOD 14.02 for anti-CCP and LOD 12.09 for RF). Six other regions with LOD scores of >1.0 overlapped between the 2 traits, on chromosomes 1p21.1, 5q15, 8p23.1, 16p12.1, 16q23.1, and 18q21.31. Evidence of linkage to anti-CCP titer but not to RF titer was found in 2 regions (chromosomes 9p21.3 and 10q21.1), and evidence of linkage to RF titer but not to anti-CCP titer was found in 2 regions (chromosomes 5p15.2 and 1q42.3). Several covariates were significantly associated with 1 or both traits, and linkage analysis exploring the covariate effects revealed striking effects of sex in modulating linkage signals for several chromosomal regions. For example, sex had a striking impact on the linkage results for both quantitative traits on chromosome 6p (P = 0.0007 for anti-CCP titer and P = 0.0012 for RF titer), suggesting a sex-HLA region interaction. CONCLUSION: Analysis of quantitative components of RA is a promising approach for dissecting the genetic heterogeneity of this complex disorder. These results highlight the potential importance of sex or other covariates that may modulate some of the genetic effects that influence the risk of specific disease manifestations.
18438851 Triple therapy in early active rheumatoid arthritis: a randomized, single-blind, controlle 2008 May OBJECTIVE: The Tight Control of Rheumatoid Arthritis study previously demonstrated that an intensive step-up disease-modifying antirheumatic drug (DMARD) treatment strategy targeting persistent disease activity was superior to routine care in the management of early rheumatoid arthritis (RA). We undertook this study to test the hypothesis that early parallel triple therapy achieves better outcomes than step-up therapy within an intensive disease management regimen. METHODS: Ninety-six patients with early RA (mean disease duration 11.5 months) were randomized to receive step-up therapy (sulfasalazine [SSZ] monotherapy, then after 3 months, methotrexate [MTX] was added, and when the maximum tolerated dosage of MTX was reached, hydroxychloroquine [HCQ] was added) or parallel triple therapy (SSZ/MTX/HCQ). All patients were assessed monthly for 12 months. If their disease activity score in 28 joints (DAS28) was > or =3.2, the dosage of DMARDs was increased according to protocol, and swollen joints were injected with triamcinolone acetonide (maximum dosage 80 mg per month). A metrologist who was blinded to the treatment allocation performed assessments every 3 months. The primary outcome measure was the mean decrease in the DAS28 score at 12 months. RESULTS: Both groups showed substantial improvements in disease activity and functional outcome. At 12 months, the mean decrease in the DAS28 score was -4.0 (step-up therapy group) versus -3.3 (parallel therapy group) (P = 0.163). No significant differences in the percentages of patients with DAS28 remission (step-up therapy group 45% versus parallel triple therapy group 33%), DAS28 good response (60% versus 41%, respectively), or American College of Rheumatology criteria for 20% improvement (ACR20) (77% versus 76%, respectively), ACR50 (60% versus 51%, respectively), or ACR70 (30% versus 20%, respectively) responses were seen. Radiologic progression was similar in both groups. CONCLUSION: This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy.
19035426 Ability of oblique foot radiographs to detect erosions in early arthritis: results in the 2008 Dec 15 OBJECTIVE: To assess the usefulness of using oblique foot radiographs in addition to posteroanterior radiographs of the hands and feet for detecting erosions in patients with recent-onset arthritis. METHODS: We included 813 patients from the prospective French ESPOIR cohort with arthritis of <6 months' duration and >or=2 swollen joints. Baseline standardized posteroanterior radiographs of the hands and feet and oblique radiographs of the feet were assessed by 2 blinded readers for erosions typical for rheumatoid arthritis (ETRA) and the Sharp score as modified by van der Heijde. RESULTS: A total of 715 complete sets were available. Mean +/- SD total Sharp scores were 3.6 +/- 6.6, 2.5 +/- 6.3, and 1.8 +/- 5 for the hand and wrist, foot, and oblique foot, respectively. ETRA were visible in 160 (22.4%) of 715 patients (95% confidence interval [95% CI] 19.4-25.6). They were seen on hand radiographs in 86 (53.7%) of 160 patients (95% CI 45.7-61.6), on posteroanterior foot radiographs in 91 (56.9%) of 160 patients (95% CI 48.8-64.6), and on oblique foot radiographs in 84 (52.5%) of 160 patients (95% CI 44.5-60.4). ETRA were visible at the feet, but not at the hands, in 74 (46%) of 160 patients (95% CI 38.4-54.3), among whom 22 (30%) had erosions only on the posteroanterior view, 16 (21%) only on the oblique view, and 36 (48.6%) on both. CONCLUSION: ETRA were found in 22.4% of patients. Adding an oblique foot radiograph identified 16 (10%) of 160 additional patients (95% CI 6-16), compared with 27.5% and 13.8% identified by adding posteroanterior radiographs of the hands and feet, respectively.
16406300 Serum insulin-like growth factor-axis and matrix metalloproteinases in patients with rheum 2006 May BACKGROUND: Insulin-like growth factor (IGF)-I plays an important role for maintaining cardiac functions. We clarified the unknown role of IGF-axis in rheumatic heart disease (RHD). METHOD: Interleukin (IL)-10, growth hormone (GH), IGF, IGF binding protein (IGFBP)-3 and matrix metalloproteinase (MMP) were measured by ELISA and zymography in 30 age range-matched normal subjects (control), 36 patients with acute phase of rheumatoid arthritis (RA) with positive rheumatoid factor (RF) and C-reactive protein (CRP), and in 43 patients with RHD with negative RF and CRP. RESULT: Compared with normal subjects, increased IL-10 level and decreased GH were found in RA group whereas unchanged IL-10 and decreased GH were found in RHD group. Compared with age range-matched normal subjects, decreased IGFBP-3, MMP-9 levels, unchanged IGF-I were found in RA group whereas decreased IGF-I levels, unchanged IGFBP3 and increased MMP-9 at age>30 years were found in RHD group. IGF-II was not changed in RA and RHD groups. CONCLUSION: These findings may imply that during inflammatory phase, the levels of anti-inflammation was high and total IGF-I and IGF bioavailability were maintained in patients with RA. Our findings in RHD may speculate that the long-term reduction of GH and IGF-I as well as the compensating effects of upregulated MMP-9 activity may be partially involved in the long-term pathogenesis from RHD to heart failure. Decreased GH, decreased IGF-I and increased MMP-9 activities may be possible diagnostic markers in RHD for developing heart failure.
16868975 Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients wi 2006 Aug OBJECTIVE: Women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis. METHODS: One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL. RESULTS: SLE patients had more proinflammatory HDL (mean +/- SD score 1.02 +/- 0.57, versus 0.68 +/- 0.28 in controls [P < 0.0001] and 0.81 +/- 0.22 in RA patients [P = 0.001 versus SLE patients]). A higher proportion of SLE patients had proinflammatory HDL: 44.7% of SLE patients versus 4.1% of controls and 20.1% of RA patients had scores >1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001). CONCLUSION: HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.
18405372 Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from 2008 Apr 11 BACKGROUND: Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. METHODS: Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. RESULTS: Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. CONCLUSION: Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.
18388524 Biologic therapy for early rheumatoid arthritis: the latest evidence. 2008 May PURPOSE OF REVIEW: To describe current therapeutic trials with biologic agents for early rheumatoid arthritis, analyzing clinical and radiographic outcomes. RECENT FINDINGS: The use of tumor necrosis factor-alpha inhibitors in combination with disease-modifying antirheumatic drugs early after the diagnosis of aggressive rheumatoid arthritis seems to provide increased clinical benefit over methotrexate or tumor necrosis factor-alpha inhibitors as monotherapy, with better outcomes in terms of faster and more extensive clinical improvement. There also seems to be an increased likelihood of low-disease activity in some cases even after tapering therapy. Control of radiographic progression appears to be most effective among early rheumatoid arthritis patients treated with combination tumor necrosis factor-alpha inhibitors and methotrexate, although radiographic outcomes are better with tumor necrosis factor-alpha inhibitor monotherapy than with methotrexate alone. SUMMARY: The addition of antitumor necrosis factor-alpha agents to traditional disease-modifying antirheumatic drugs in early rheumatoid arthritis is a novel strategy which follows the principle of early and aggressive therapeutic intervention. Results from recent trials show greater levels of disease control. The impact on long-term safety and cost-efficacy are factors which will need to be better characterized over time.
17711866 Methotrexate combined with isoniazid treatment for latent tuberculosis is well tolerated i 2008 Apr OBJECTIVES: Reactivation of Mycobacterium tuberculosis (TB) is a significant problem with all available tumour necrosis factor (TNF) antagonists when used to treat rheumatoid arthritis (RA), psoriatic arthritis, psoriasis and other inflammatory diseases. Concerns have been raised regarding the appropriate management of patients with latent TB (LTB) exposure (or active TB infection) before initiating TNF antagonists as the safety data of combined treatment with two potentially hepatotoxic medications, methotrexate (MTX) and isoniazid (INH), is lacking. The goal of this study was to investigate the toxicity of MTX and INH treatment in patients with RA before initiating TNF antagonists. METHODS: To investigate the toxicity of MTX and INH treatment in patients with RA we performed a retrospective chart review of patients seen at the Bellevue Hospital Arthritis Clinic in New York City between 2002 and 2006. Forty-four patients who were concomitantly treated with both drugs were included. The primary outcome investigated was increase in liver function tests (LFT). RESULTS: Transient increases in LFT were seen in 11% of patients, but in no case was this more than twice the upper limit of normal values. All abnormal LFT resolved spontaneously without intervention. In addition, no patient has developed signs or symptoms of TB reactivation. CONCLUSIONS: The use of INH for LTB was well tolerated in patients with RA on a background regimen of MTX. While the risks and benefits of all treatment must always be considered, in our experience the additive risk of INH to MTX in terms of hepatotoxicity was low. None the less it is prudent to follow LFT closely on patients taking this combination.
17633096 [2-year complete remission after withdrawal of methotrexate in a rectal methotrexate-assoc 2007 Jun A 71-year-old man, who had been receiving methotrexate (MTX) and prednisolone for the treatment of rheumatoid arthritis, was admitted to our hospital in August of 2004 with rectal hemorrhage. Histological examination of an ulcerative lesion of the rectum revealed diffuse large B-cell lymphoma (DLBCL). Chemotherapy with the CHOP regimen with dose reduction following cessation of MTX was initiated. However, the patient experienced septic shock secondary to febrile neutropenia and was then followed up without chemotherapy. The DLBCL rectal lesion regressed spontaneously thereafter and had resolved completely without treatment 2 years after the initial presentation, suggesting that the withdrawal of MTX led to regression of the DLBCL. The DLBCL in our patient is compatible with MTX-associated lymphoproliferative disorders. Immunoglobulin gene rearrangement and Epstein-Barr virus (EBV) infection found in tumor cells indicated that the EBV was involved in the monoclonal proliferation of B-cells in this patient whose immune function was suppressed by MTX therapy.