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ID PMID Title PublicationDate abstract
21875874 Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monothera 2011 Dec OBJECTIVES: To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed. METHODS: Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified. RESULTS: Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX. CONCLUSIONS: Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.
21983397 [Systemic autoimmune disorders and pregnancy]. 2011 Oct 23 The coincidence of systemic autoimmune diseases and pregnancy may modify the outcome of the disease and the pregnancy due to the background immunologic and hormonal processes. The great majority of patients with autoimmune diseases are young females in their reproductive years, willing to have babies. Consequently, we have to prepare for this special situation. Our concept on childbearing in autoimmune women has changed within the last 30 years. Earlier, systemic lupus erythematosus flared in about 50% of patients during pregnancy, but the flare rate has significantly decreased recently. This improvement can be attributed to increased attention to low diseases activity at the time of conception, which might reduce to the half of the risk for flare. Tight control of patients and appropriate use of corticosteroids also contribute to the better results. The adequate use of anti-thrombotic agents resulted in a significant amelioration of pregnancy outcome in antiphospholipid syndrome. The earlier use of methotrexate and the introduction of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis have changed the natural characteristics of the disease. The increase in remission rate indirectly has beneficial effect on the number of planned and carried out pregnancies. Authors review the connection between systemic autoimmune disorders and pregnancy as well as the possibilities of medical treatment of such diseases during pregnancy.
23256105 Incidence of influenza-like illness into a cohort of patients affected by chronic inflamma 2012 Dec 11 This study aimed to evaluate the incidence of influenza-like illness (ILI), from October 2009 to May 2010, in a group of patients suffering from chronic inflammatory rheumatism and treated with biological therapies. At the end of 2009-2010 influenza season, 159 patients under biological therapies answered to a questionnaire distributed 8 months before and were deeply interviewed. The group included 69 men and 90 women (mean age 47.6); forty-nine suffering from rheumatoid arthritis, 61 with psoriatic arthritis, 32 with ankylosing spondylitis and 17 with other spondyloarthritis; 146 patients were treated with anti-TNF-α, 7 with rituximab and 6 with abatacept; 128 patients assumed DMARDs and 72 patients assumed low dose of steroids. A case of ILI was identified by anamnestic findings and according to the case definitions commonly used in Europe. Seventeen percent of the considered population reported at least one episode of ILI during the monitoring period; none of the patients during the acute influenza attack suffered particularly severe symptoms and no one was hospitalized due to complications. Despite the diversity among the considered subgroups, the statistical analysis did not show any significant difference when incidence of ILI was considered for different disease, different biological agent and different association therapy. None of the examined variables resulted statistically significant concerning the relative risk evaluation. The incidence of ILI into a cohort of 159 patients treated with biological agents during the influenza season 2009-2010 resulted higher than the value reported in a wide sample of Italian population in the same period. However, the pandemic impact was not heavy among the studied patients, considering that no important complications or hospitalizations have been reported.
23176102 A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid art 2012 Nov 23 INTRODUCTION: Interleukin (IL)-21 is a member of type I cytokine family. Recent studies indicate that IL-21 can promote T follicular helper (Tfh) cell differentiation and survival, a specialized T cell subset which provides help for B cell. It can also regulate the activation, proliferation and differentiation of human B cell and immunoglobulin (Ig) production as well as isotype switching of plasma cell. Rheumatoid arthritis (RA) is characterized by auto-antibodies overproduction such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, suggesting a pivotal role of Tfh cell and B cell in the pathogenesis of RA. This study aimed to investigate whether IL-21 had a regulatory effect on Tfh cell and B cell in RA. METHODS: Serum IL-21 concentrations were measured by ELISA. The correlations between serum IL-21 levels and clinical features of RA patients were analyzed by Spearman's rank test. The percentages of Tfh-like cells, IL-21 receptor (R) expression on Tfh-like cells and B cells in peripheral blood (PB) were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) were stimulated by rIL-21 (100 ng/ml) in the presence or absence of anti-CD40 and/or anti-IgM, and changes of IL-21R, activation-associated surface markers (CD25, CD69 and CD40), the proliferation, apoptosis and differentiation of B cells were analyzed by flow cytometry. Production of IgG and IgM in the culture supernatants was determined by ELISA. RESULTS: The results showed that the serum IL-21 levels in RA patients were significantly higher than that of healthy controls (HC). IL-21 concentrations were positively correlated with 28-joint count disease activity score (DAS28) and anti-CCP antibody in RA patients with high IL-21 levels. Furthermore, the frequencies of peripheral CXCR5+PD-1+CD4+ Tfh-like cells markedly increased in RA patients and the percentages of Tfh-like cells were positively correlated with DAS28 and anti-CCP antibody levels. Moreover, elevated IL-21 levels were also correlated with the frequencies of Tfh-like cells. IL-21R expression on both Tfh-like cells and B cells were significantly enhanced in RA patients. In cultures vitro, exogenous IL-21 upregulated IL-21R expression and activation-associated surface markers on B cells and promoted more B cell proliferation in RA than in HC. This IL-21-mediated effect could be reversed by IL-21R-specific neutralizing antibody. Importantly, IL-21 promoted more differentiation of B cell into plasmablast and higher levels of IgG and IgM production in RA than in HC. CONCLUSIONS: Increased serum IL-21 levels in RA patients correlate with DAS28, anti-CCP antibody and frequencies of Tfh-like cells. IL-21 supports B cell activation, proliferation and antibody secretion via IL-21R pathway. Thus, IL-21 may be involved in the pathogenesis of RA and antagonizing IL-21 could be a novel strategy for the therapy of RA.
21859707 Indirect and mixed treatment comparisons in arthritis research. 2011 Sep Evidence for the efficacy of biologic therapies in inflammatory arthritis comes overwhelmingly from placebo-controlled trials. Increasingly, however, authorities responsible for purchasing and reimbursement have tried to determine whether there are differences between these powerful new therapies, which would lead them to recommend some in preference to others, either on grounds of efficacy or cost-effectiveness. In the absence of head-to-head trial comparisons, indirect comparisons may be used. Furthermore, network meta-analysis, also known as mixed treatment comparisons can combine information from trials in a connected network. These methods allow inferences about head-to-head comparisons even when there is little or no head-to-head evidence, which has caused some concern. In this article we briefly review these methodologies and describe results from recent applications to inflammatory arthritis in the clinical literature. We then focus on how the methodologies are used in decision making, taking as an illustration some recent technology appraisals conducted by the National Institute for Health and Clinical Excellence in the UK. We conclude that, in practice, the key decisions have been based on results from placebo-controlled trials.
23156730 [The effect of Hsp72 on IL-6, IL-8 expression and activation of NF-kappaB in synoviocytes 2012 Jul OBJECTIVE: To investigate the effects of heat shock protein 72 (Hsp72) on the expression of IL-6 and IL-8 and activation of NF-kappaB in synoviocytes from patients suffered from rheumatoid arthritis (RA). METHODS: IL6 and IL8 concentrations in culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). Nuclear translocation of NF-kappaB and degradation of the inhibitory protein IkappaBalpha were examined using immunohistochemistry and Western blot. RESULTS: Hsp72 down-regulated IL-6 and IL-8 production in RA synoviocytes induced by tumor necrosis factor-alpha (TNF-alpha). Hsp72 inhibited nuclear translocation of NF-kappaB and degradation of IkappaBalpha induced by TNF-alpha. CONCLUSION: Hsp72 has an anti-inflammatory effect on RA by down-regulation of IL-6 and IL-8 in synoviocytes, which is mediated through inhibiting the activation of NF-KalphaB signal pathways.
20801615 Five cases of failure of the tibial polyethylene insert locking mechanism in one design of 2011 Sep We describe 5 cases of failure of the locking mechanism of the polyethylene insert and tibial base-plate in one design of constrained condylar knee prosthesis due to disengagement of the locking screw. Loosening of the screw is believed to occur because of a counterclockwise torque created by the axial rotation of the femur on the tibia that occurs as the knee extends during gait. This torque is transmitted via the highly rotationally constrained femoral housing and tibial post to the locking screw. These failures suggest that an alternative locking mechanism should be considered for this prosthesis.
23244167 MSRA polymorphism is associated with the risk of rheumatoid arthritis in a Chinese populat 2013 OBJECTIVES: The expression of receptor activator of methionine sulfoxide reductase A (MSRA) and that of receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) are closely related to rheumatoid arthritis (RA). Our aim was to confirm whether MSRA and RANKL polymorphisms play a role in RA in a Chinese population. METHODS: We investigated the presence of MSRA rs10903323 G/A and RANKL rs7984870 C/G polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: When the MSRA rs10903323 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly increased risk for RA. In the dominant model, when the MSRA rs10903323 GG homozygote genotype was used as the reference group, the GA/AA genotypes were associated with a significantly increased susceptibility to RA. The RANKL rs7984870 C/G polymorphism was not associated with a risk for RA. In stratification analyses, a significantly increased risk for RA associated with the MSRA rs10903323 GA genotype was evident among male patients, older patients, C-reactive protein (CRP)-positive patients, and anti-cyclic citrullinated peptide (anti-CCP) negative patients compared with the MSRA rs10903323 GG genotype. CONCLUSIONS: These findings suggest that the MSRA rs10903323 G/A variant allele is associated with RA development, especially among male patients, older patients, CRP-positive patients, and anti-CCP negative patients.
21304427 Doppler ultrasonography and computed tomography angiography demonstrate positional occlusi 2011 Oct 15 STUDY DESIGN: Case report of a patient with rheumatoid arthritis (RA) and a positional occlusion of the left vertebral artery (VA). OBJECTIVE: To describe the utility of Doppler ultrasonography and computed tomography (CT) angiography for the diagnosis of positional VA occlusion. SUMMARY OF BACKGROUND DATA: In previous reports of positional VA occlusion in RA, angiography has been used for the diagnosis. However, it is difficult to demonstrate the three-dimensional relationship between the arteries and the bone structure with angiography. METHODS: An 83-year-old man with a 20-year history of RA complained of severe vertigo when he leaned his head in the left-anterior direction. CT angiography in the neutral position revealed that the left VA was pinched between the posterior rim of the transverse foramen of C1 and the transverse process of C2. Doppler ultrasonography demonstrated positional VA occlusion and a severe reduction in blood flow at the position that most readily induces vertigo. Because the space between the transverse foramens of left C1 and C2 was reduced with the destruction of the left C1/C2 lateral masses, slight rotation, and anterior shift of C1 led to the occlusion of the VA. RESULTS: After posterior O-C2 fusion at the reduced position, the VA occlusion and vertigo disappeared. CONCLUSION: Doppler ultrasonography and CT angiography allow valuable measurements in the diagnosis of positional VA occlusion. The one-sided destruction of the C1/C2 lateral masses might be a causal factor for VA occlusion in RA. This is the first report of a new pathomechanism underlying positional VA occlusion demonstrated with three-dimensional CT angiography.
21515464 [Effect of NK-22 cells in the synovial fluid of patients with rheumatoid arthritis on the 2011 Apr OBJECTIVE: To investigate the effect of NK-22 cells isolated from the synovial fluid (SF) of patients with rheumatoid arthritis (RA) on the proliferation of fibroblast-like synoviocytes and explore its possible mechanism. METHODS: The proportions of NK-22 cells in the peripheral blood (PB) and the SF of 20 RA patients and 20 healthy individuals were determined by flow cytometry. NK-22 cells in the SF sorted by flow cytometry were cultured for two weeks followed by a 4-h stimulation with 20 ng/ml phorbol 12-myristate 13-acetate and 0.5 µ mol/L ionomycin. The culture supernatant of NK-22 cells was then harvested, in which the levels of IL-22 and TNF-α were measured by ELISA. The fibroblast-like synoviocytes were exposed to the culture supernatant for 24, 48, 72, and 96 h, and the changes in the cell proliferation were detected by MTT assay. RESULTS: RA patients showed a significantly greater proportion of NK-22 cells in both the SF and PB than the normal control subjects (P<0.05). NK-22 cells sorted by flow cytometry reached a purity exceeding 90%, and the levels of IL-22 and TNF-α in the culture supernatant of NK-22 cells cultured for two weeks were 941.16 pg/ml and 368.1 pg/ml, respectively. The culture supernatant of NK-22 cells caused a rapid proliferation of the fibroblast-like synoviocytes at 24, 48, 72, and 96 h after the exposure. CONCLUSION: NK-22 cells in the SF of RA patients can promote the proliferation of fibroblast-like synoviocytes possibly due to the capacity of NK-22 cells to produce IL-22 and TNF-α.
21370227 Examining the overlap between genome-wide rare variant association signals and linkage pea 2011 Jun OBJECTIVE: With the exception of the major histocompatibility complex (MHC) and STAT4, no other rheumatoid arthritis (RA) linkage peak has been successfully fine-mapped to date. This apparent failure to identify association under peaks of linkage could be ascribed to the examination of common variation, when linkage is likely to be driven by rare variants. The purpose of this study was to investigate the overlap between genome-wide rare variant RA association signals observed in the Wellcome Trust Case Control Consortium (WTCCC) study and 11 replicating RA linkage peaks, defined as regions with evidence for linkage in >1 study. METHODS: The WTCCC data set contained 40,482 variants with minor allele frequency of ≤0.05 in 1,860 RA patients and 2,938 controls. Genotypes of all rare variants within a given gene region were collapsed into a single locus and a global P value was calculated per gene. RESULTS: The distribution of rare variant signals (association P≤10(-5)) was found to differ significantly between regions with and without linkage evidence (P=2×10(-17) by Fisher's exact test). No significant difference was observed after data from the MHC region were removed or when the effect of the HLA-DRB1 locus was accounted for. CONCLUSION: The results suggest that rare variant association signals are significantly overrepresented under linkage peaks in RA, but the effect is driven by the MHC. This is the first study to examine the overlap between linkage peaks and rare variant association signals genome-wide in a complex disease.
22016872 Tissue necrosis after use of enoxaparin in total knee arthroplasty: a case report. 2011 Aug Tissue necrosis at the injection site of enoxaparin is a rare adverse effect. Most of the reported clinical course of this necrosis is uneventful. Here we review a case of tissue necrosis that developed after use of enoxaparin and required debridement followed by reconstructive surgery. Until now, such a case has not been reported in the English-language literature. As enoxaparin is being used more often for prevention of deep vein thrombosis in patients who undergo arthroplasty surgery, awareness and recognition of this adverse event and careful supervision of all patients who receive this medication are essential.
22360682 Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease 2012 Jul Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogen-activated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+896A>G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+896A>G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patients.
22264593 Outcomes of nonstenting percutaneous coronary intervention in patients with rheumatoid art 2012 Apr 15 The aim of the present study was to explore the outcomes of percutaneous coronary intervention (PCI) in patients with rheumatoid arthritis (RA) and coronary heart disease. We identified 25,367 patients from the National Health Insurance Research Database who underwent nonstenting PCI in Taiwan in 2007. Of these patients, 240 had been diagnosed with RA. As a comparison group, we selected 1,200 patients who were matched with the study group by gender and age. We performed conditional logistic regression analysis to compare the outcomes of PCI between the 2 groups. We found no significant differences in the rates of in-hospital mortality (2.5% vs 3.1%, p = 0.628), 90-day readmission for PCI (8.3% vs 7.2%, p = 0.559), or 365-day readmission for PCI (22.5% vs 19.2%, p = 0.236) between the patients with and without RA. Similarly, the conditional logistic regression analyses revealed that patients with RA had no greater adjusted odds of in-hospital mortality (odds ratio 0.94, 95% confidence interval 0.37 to 2.36), 90-day readmission for PCI (odds ratio 1.20, 95% confidence interval 0.37 to 2.36), and 365-day readmission for PCI (odds ratio 1.30, 95% confidence interval 0.92 to 1.83) than the comparison group. In conclusion, our study did not find an increased risk of adverse outcomes among patients with RA after PCI.
22886739 Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor i 2012 Nov OBJECTIVE: To determine whether the differences in the modes of action and safety profiles of individual tumor necrosis factor inhibitors (TNFi) translate into differential mortality risks, as investigated in etanercept, infliximab, and adalimumab. METHODS: Data on patients with rheumatoid arthritis (RA) identified in the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]) in whom first-ever treatment with a biologic agent (etanercept [n = 2,686], infliximab [n = 2,027], or adalimumab [n = 1,609]) was initiated between 2003 and 2008 were linked to national Swedish registers to get information on deaths from any cause, demographic features, RA characteristics, comorbid conditions, and concurrent treatment at the start of TNFi treatment. Hazard ratios (HRs) were modeled using multivariable adjusted and weighted Cox models. RESULTS: During 19,118 person-years of followup, 211 patients died (3.3%; 1.1 deaths per 100 person-years); 85% of the deaths occurred among patients who had been exposed to only one TNFi. We found no statistically significant difference in overall mortality rates across the exposure groups, regardless of adjustment and modeling approach (for infliximab versus etanercept, HR 1.1 [95% confidence interval (95% CI) 0.7-1.7], and for adalimumab versus etanercept, HR 1.3 [95% CI 0.9-2.0]). CONCLUSION: Overall, we noted no statistically significant difference in mortality rates between the 3 TNF inhibitors under study. Further studies need to examine whether certain subsets of patients are at increased risk of death with specific TNFi.
23259653 Effective initial and long-term prednisone in doses of less than 5 mg/day to treat rheumat 2012 The efficacy of initial and long-term prednisone < 5 mg/ day in treatment of rheumatoid arthritis (RA) by one academic rheumatologist over 25 years from 1980 to 2004 is summarized. Patient responses were assessed using a multidimensional health assessment questionnaire (MDHAQ), completed by all patients at all visits in the infrastructure of care. A database was maintained of all visits, which included medications and scores for physical function, pain, patient global estimate of status, and routine assessment of patient index data (RAPID3), an index of these 3 measures. Prednisone doses were higher in patients with more severe MDHAQ/RAPID3 scores, as expected, although formal criteria were not used to determine the initial dose. Similar improvements were seen in clinical status over 12 months in patients treated with < 5 vs ≥ 5 mg/day prednisone and maintained for > 8 years. Adverse effects were primarily bruising and skin-thinning; levels of hypertension, diabetes, and cataracts were not higher than expected, including in 148 patients monitored over > 4 years, 75 over > 8 years. Prednisone at initial and long-term doses of < 5 mg/day appears acceptable and effective for many patients with RA at this time, although further clinical trials and long-term observational studies are needed to optimize treatment of patients with RA with low-dose prednisone. The data also illustrate that MDHAQ scores in usual clinical care can be used to document results of therapy over long periods with no extra work for the physician.
21294106 American College of Rheumatology/European League Against Rheumatism provisional definition 2011 Mar OBJECTIVE: Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. METHODS: A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. RESULTS: Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (e.g., tender and swollen joint counts, C-reactive protein [CRP] level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year followup data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (a) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤ 1, or (b) when the score on the Simplified Disease Activity Index is ≤ 3.3. CONCLUSION: We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.
21930442 Liver stiffness correlates with methotrexate cumulative dose in patients with rheumatoid a 2012 Feb BACKGROUND: Liver stiffness values were recently proposed to identify patients with methotrexate-induced liver fibrosis. Aim of this study was to assess the clinical and laboratory determinants of the association between liver stiffness, measured by transient elastography, and methotrexate treatment in patients with rheumatoid arthritis in the absence of other factors contributing to liver damage and fibrosis. METHODS: 100 patients with rheumatoid arthritis, with a cumulative methotrexate dose ranging from 1530 to 13,000 mg over a mean period of 7.07±3.89 yrs, were retrospectively evaluated. RESULTS: The average liver stiffness value in the whole population was 4.93±1.8 kPa, excluding the presence of significant fibrosis. At univariate analysis, a significant correlation was found between liver stiffness and methotrexate cumulative dose, duration of treatment, alanine transaminases levels, body mass index, gamma glutamyl-transpeptidase and the presence of steatosis. At multivariate analysis, a significant association was detected only between liver stiffness and methotrexate cumulative dose. Out of 11 patients with liver stiffness >7.0 kPa, five were subjected to liver biopsy and mild or moderate perisinusoidal fibrosis was detected in two patients with a cumulative dose >4000 mg and liver stiffness >9 kPa. CONCLUSIONS: Chronic methotrexate treatment induces a progressive increase in liver stiffness corresponding to mild or moderate perisinusoidal fibrosis for values >9 kPa.
22526833 A review of tocilizumab treatment in 122 rheumatoid arthritis patients included in the Tsu 2013 Mar OBJECTIVES: Biologics have transformed the treatment of rheumatoid arthritis. Clinical remission is now the goal. We sought to verify whether the administration of tocilizumab-a biologic-can help to achieve current treatment goals. METHODS: Using data from the Tsurumai Biologics Communication Registry for 122 patients treated with tocilizumab, we evaluated changes in DAS28-ESR at 12 months after initiation, and also evaluated remission rates defined using conventional and new Boolean-based remission criteria. We divided 50 patients who had received tocilizumab as a first-line treatment into two groups [disease duration at baseline of 12 months or less (≤12 M) and more than 12 months (>12 M)]. RESULTS: At 12 months after initiation, there was no difference in DAS28-ESR, and remission rates based on the conventional criterion were also comparable (50 % in both groups). However, under the new criterion, remission was 50.0 % in the ≤12 M group against 12.5 % in the >12 M group (p = 0.0181). Among the individual components of the new remission criterion, the small proportion of patients in the >12 M group with a patient global assessment (PtGA) of ≤1 had a particularly strong influence on the remission rate for that group, but this component was not as important for the ≤12 M group. CONCLUSIONS: When used as a first-line biological drug for patients with early-stage RA (≤12 M), tocilizumab appears to provide high rates of remission under the Boolean-based remission criterion, which were strongly affected by the PtGA.
22100630 Soluble triggering receptor expressed on myeloid cells-1 as a new therapeutic molecule in 2012 Feb Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified cell surface receptor that is expressed mainly on monocytes and neutrophils, and plays an important role as an amplifier of inflammatory response in acute and chronic inflammatory conditions. Recent studies suggested that TREM-1 contributes to the pathogenesis of rheumatoid arthritis (RA) and therefore TREM-1 could be a new therapeutic target in RA. In addition to its membrane-bound form, a soluble form of TREM-1 (sTREM-1) exists that is liberated by the proteolytic cleavage of membrane-bound form. This soluble form works as decoy receptor to prevent the binding of its ligand to membrane-bound TREM-1 and to inhibit the effect of TREM-1 activation. Proteolytic cleavage of TNF receptor (TNFR) has been reported and soluble TNFR are capable of binding and neutralizing TNF, thus working as natural TNF antagonist. Currently, etanercept, a soluble TNF-receptor fusion protein has been widely used to treat RA. In this report, we suggest that sTREM-1 can be used as a new therapeutic molecule in RA.