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ID PMID Title PublicationDate abstract
18971804 [Pulmonary manifestation of rheumatoid arthritis]. 2008 Oct INTRODUCTION: Lung disease is the most frequent and among the most severe extra-articular manifestation of rheumatoid arthritis (RA). Several interesting advances have been made in recent years in our understanding of this respiratory disease. STATE OF ART: 1. The induction of BALT responsible for follicular lymphoid infiltrates has been demonstrated in the wall of respiratory bronchioles. These lymphoid infiltrates are similar to synovial and skin cellular infiltrates and secrete specific markers of RA (citrullinated proteins). These data strongly suggest a common pathogenic mechanism for RA in the joints and in other sites, such as the lung. 2. Improvements in high resolution computed tomography (HR- CT) increased the sensitivity of diagnosis. CT evidence of pulmonary disease is present in 50% of RA patients, but only 10% of these patients have clinical symptoms. The different lung manifestations, frequently combined, have been clearly described: pulmonary nodules (20%); small airways disease (30%): bronchiolitis, bronchiolectasis, and bronchiectasis; diffuse interstitial pneumonia of various types (20%). 3. Predictors of progression and therapeutic response remain unknown. Therefore treatment is empirical and based on usual indications and on drugs used in idiopathic fibrosis and other connective tissue pulmonary pathologies. CONCLUSIONS: New biological drugs such as TNF blocking agents or anti CD20 antibody could be beneficial. Infections and drug-induced pneumonitis are not described in this review but must be considered systematically when an RA patient presents with lung involvement.
18633128 Melanoma inhibitory activity, a biomarker related to chondrocyte anabolism, is reversibly 2009 Jun OBJECTIVE: In mice, melanoma inhibitory activity (MIA) is a chondrocyte-specific molecule with similar regulation to collagen type II. As MIA is a small secreted protein, its value as cartilage biomarker in human inflammatory arthritis was assessed. METHODS: MIA tissue distribution was studied by quantitative PCR and immunohistochemistry. The regulation of MIA production was studied in vivo in rheumatoid arthritis (RA) (n = 37) and spondyloarthritis (SpA) (n = 30) synovial fluid (SF), and in vitro in alginate embedded human chondrocytes. Therapeutic modulation of serum MIA was evaluated during tumour necrosis factor (TNF)alpha and interleukin (IL)1 blockade in RA. RESULTS: MIA was primarily expressed by chondrocytes in the human joint. SF MIA levels were lower in RA than in SpA despite similar levels of overall synovial inflammation. Further analysis indicated that these levels were inversely correlated with the degree of joint inflammation in RA, but not in SpA, and that the levels of TNFalpha and IL1beta were significantly increased in RA versus SpA. Accordingly, these proinflammatory cytokines suppressed MIA mRNA and protein in cultured chondrocytes. This suppression was paralleled by suppression of cartilage anabolism as assessed by collagen type 2 and aggrecan mRNA. Treatment of patients with RA with TNF blockade or IL1 blockade induced an increase of serum MIA levels. CONCLUSION: The decreased levels of MIA in the inflamed RA joint and the coregulation of MIA and cartilage matrix molecules by proinflammatory cytokines indicate that joint inflammation in RA not only drives accelerated cartilage degradation but also suppresses cartilage anabolism. This inflammation-driven suppression is reversible in vivo.
16572447 Synovial membrane cytokine expression is predictive of joint damage progression in rheumat 2006 Apr OBJECTIVE: The primary aim of this prospective 2-year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane. METHODS: Patients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin-1beta (IL-1beta), IL-10, IL-16, IL-17, RANKL, tumor necrosis factor alpha (TNFalpha), and interferon-gamma (IFNgamma) messenger RNA (mRNA) expression was determined by quantitative reverse transcription-polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis. RESULTS: Sixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL-1beta, TNFalpha, IL-17, and IL-10 were predictive of damage progression. IL-17 was synergistic with TNFalpha. TNFalpha and IL-17 effects were most pronounced with shorter disease duration, and IL-1beta effects were most pronounced with longer disease duration. IFNgamma was protective. These factors explained 57% of the MRI joint damage progression over 2 years. CONCLUSION: We have demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA. The findings for IL-1beta and TNFalpha are consistent with results of previous clinical research, but the protective role of IFNgamma, the differing effects of disease duration, and IL-17-cytokine interactions had only been demonstrated previously by animal and in vitro research. These findings explain some of the variability of joint damage in RA and identify new targets for therapy.
18593757 Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort stud 2009 Apr OBJECTIVES: The "fetal origins of adult disease" hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual's future risk of rheumatoid arthritis (RA). METHODS: The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses' Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18. RESULTS: In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2-3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6). CONCLUSIONS: In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.
17223662 Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide stimulation is 2007 Aug OBJECTIVES: (1) To assess innate ex vivo production of interleukin 1beta (IL1beta) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent-onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess the association of ex vivo IL1beta and IL1Ra production with progression of joint damage in RA; (3) to determine whether differences in ex vivo IL1beta production are explained by distribution of the IL1beta single nucleotide polymorphism C-511T. METHODS: Levels of IL1beta and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide) and distribution of IL1beta C-511T were compared in 76 patients with recent-onset RA who had received no disease-modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based on ex vivo IL1beta and IL1Ra production were calculated. Association of ex vivo IL1beta and IL1Ra production with progression of joint damage (Sharp-van der Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics. RESULTS: Patients with recent-onset RA showed lower ex vivo IL1beta and higher ex vivo IL1Ra production than healthy controls (p<0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1beta-producers and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with progression of joint damage (p = 0.01). The IL1beta C-511T genotype distribution was not significantly different between patients and controls. CONCLUSIONS: Patients with recent-onset RA had decreased ex vivo IL1beta production and increased ex vivo IL1Ra production compared with controls. Ex vivo IL1Ra production is an independent predictor of progression of joint damage in recent-onset RA.
17068067 Stable occurrence of knee and hip total joint replacement in Central Finland between 1986 2007 Mar BACKGROUND: Total joint replacement (TJR) surgery is an important severe long-term outcome of rheumatoid arthritis, but relatively little is known about changes of its incidence in patients with rheumatoid arthritis over the past two decades. METHODS: A population-based, retrospective, incidence case review was conducted to analyse the frequency of primary TJR surgery of the knee and hip in all patients, and specifically in patients with rheumatoid arthritis in Central Finland between 1986 and 2003. Patients with TJR surgery of the knee and hip were identified in hospital databases over the 18-year period. Age-standardised incidence rate ratios for the primary TJR of the knee and hip were calculated, stratified to sex and diagnosis, with 1986 as the reference value. RESULTS: In patients without rheumatoid arthritis the age-adjusted incidence rate ratios (with 95% CI) for TJR of the knee increased 9.8-fold from 1986 to 2003 in women and men, and for TJR of the hip 1.8-fold in women and 2-fold in men. By contrast, no meaningful change was seen over this period, in age-adjusted incidence rate ratios for TJR of the knee or hip in patients with rheumatoid arthritis, ranging from 0.7 to 1.2 in 2003 compared with 1986. CONCLUSION: The prevalence of TJR surgery has increased 2-10-fold in patients without rheumatoid arthritis patients, associated with an ageing population, but has not increased in patients with rheumatoid arthritis between 1986 and 2003. These data are consistent with emerging evidence that long-term outcomes of rheumatoid arthritis have improved substantially, even before the availability of biological agents.
19032813 Erythrocyte sedimentation rate and C-reactive protein levels are poorly correlated with cl 2008 Sep OBJECTIVE: To determine the patterns and correlation of elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels with outcome measures in rheumatoid arthritis (RA), and compare it to systemic lupus erythematosus (SLE) and osteoarthritis (OA) patients. METHODS: Brooklyn Outcomes Arthritis Registry Database (BOARD) was analyzed to determine both first visit and mean values of ESR and CRP, along with disease activity measures in each patient. Data were analyzed with descriptive statistics and correlations. RESULTS: Among all patients half of all (n=377) ESR results were elevated. In RA patients the proportions of having both ESR and CRP elevated, both within normal levels, and only one elevated and the other normal were similar. For all diagnosis, both ESR and CRP have weak positive correlations with disease activity measures measured at first visits. ESR and CRP have a modest positive correlation with each other across all three disease groups. CONCLUSION: In this cohort of RA, SLE and OA patients, ESR and CRP values were modestly correlated with each other and they were weakly correlated with disease activity measures. These data suggest that another look at the role of ESR and CRP as markers of inflammation in RA patients seen in routine care may be in order.
16762555 Side-chain and backbone amide bond requirements for glycopeptide stimulation of T-cells ob 2006 Sep 1 Collagen induced arthritis (CIA) is the most studied animal model for rheumatoid arthritis and is associated with the MHC class II molecule Aq. T-cell recognition of a peptide from type II collagen, CII256-270, bound to Aq is a requirement for development of CIA. Lysine 264 is the major T-cell recognition site of CII256-270 and CIA is in particular associated with recognition of lysine 264 after posttranslational hydroxylation and subsequent attachment of a beta-D-galactopyranosyl moiety. In this paper we have studied the structural requirements of collagenous glycopeptides required for T-cell stimulation, as an extension of earlier studies of the recognition of the galactose moiety. Synthesis and evaluation of alanine substituted glycopeptides revealed that there are T-cells that only recognise the galactosylated hydroxylysine 264, and no other amino acid side chains in the peptide. Other T-cells also require glutamic acid 266 as a T-cell contact point. Introduction of a methylene ether isostere instead of the amide bond between residues 260 and 261 allowed weaker recognition by some, but not all, of the T-cells. Altogether, these results allowed us to propose a model for glycopeptide recognition by the T-cells, where recognition from one or the other side of the galactose moiety could explain the different binding patterns of the T-cells.
16079166 Simultaneous development of acute phase response and autoantibodies in preclinical rheumat 2006 Apr OBJECTIVE: To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA). METHODS: For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis. RESULTS: IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients. CONCLUSION: Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.
16984940 Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: 2007 Apr BACKGROUND: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored. OBJECTIVES: To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases). METHODS: Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control). RESULTS: The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87-93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42-50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples. CONCLUSIONS: In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.
18086727 Abatacept inhibits progression of structural damage in rheumatoid arthritis: results from 2008 Aug OBJECTIVE: Assess the effect of abatacept on progression of structural damage over 2 years in patients with rheumatoid arthritis who had an inadequate response to methotrexate. METHODS: 539 patients entered an open-label extension of the AIM (Abatacept in Inadequate responders to Methotrexate) trial and received abatacept. Radiographic assessment of the hands and feet was performed at baseline, year 1 and year 2. At year 2, each patient's radiographs were scored for progression blinded to sequence and treatment allocation. RESULTS: In patients treated with abatacept for 2 years, greater reduction in progression of structural damage was observed in year 2 than in year 1. The mean change in total Genant-modified Sharp scores was reduced from 1.07 units in year 1 to 0.46 units in year 2. Similar reductions were observed in erosion and joint space narrowing scores. Following 2 years of treatment with abatacept, 50% of patients had no progression of structural damage as defined by a change in the total score of < or =0 compared with baseline. 56% of patients treated with abatacept had no progression during the first year compared with 45% of patients treated with placebo. In their second year of treatment with abatacept, more patients had no progression than in the first year (66% vs 56%). CONCLUSIONS: Abatacept has a sustained effect that inhibits progression of structural damage. Furthermore, the mean change in radiographic progression in patients treated with abatacept for 2 years was significantly lower in year 2 versus year 1, suggesting that abatacept may have an increasing disease-modifying effect on structural damage over time.
19035519 Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early 2008 Dec OBJECTIVE: To analyze the expression, regulation, and biologic relevance of Toll-like receptors (TLRs) 1-10 in synovial and skin fibroblasts and to determine the expression levels of TLRs 2, 3, and 4 in synovial tissues from patients with early rheumatoid arthritis (RA), longstanding RA, and osteoarthritis (OA). METHODS: Expression of TLRs 1-10 in RA synovial fibroblasts (RASFs), OASFs, and skin fibroblasts was analyzed by real-time polymerase chain reaction (PCR). Fibroblasts were stimulated with tumor necrosis factor alpha, interleukin-1beta (IL-1beta), bacterial lipopeptide, poly(I-C), lipopolysaccharide, and flagellin. Production of IL-6 was determined by enzyme-linked immunosorbent assay and induction of TLRs 2-5, matrix metalloproteinases (MMPs) 3 and 13 messenger RNA by real-time PCR. Expression of TLRs 2-4 in synovial tissues was analyzed by immunohistochemistry. RESULTS: Synovial fibroblasts expressed TLRs 1-6, but not TLRs 7-10. Among the expressed TLRs, TLR-3 and TLR-4 were the most abundant in synovial fibroblasts, and stimulation of synovial fibroblasts with the TLR-3 ligand poly(I-C) led to the most pronounced increase in IL-6, MMP-3, and MMP-13. In contrast, skin fibroblasts did not up-regulate MMP-3 or MMP-13 after stimulation with any of the tested stimuli. In synovial tissues from patients with early RA, TLR-3 and TLR-4 were highly expressed and were comparable to the levels of patients with longstanding RA. These expression levels were elevated as compared with those in OA. CONCLUSION: Our findings of high expression of TLRs, particularly TLRs 3 and 4, at an early stage of RA and the reactivity of synovial fibroblasts in vitro to TLR ligands suggest that TLR signaling pathways resulting in persistent inflammation and joint destruction are activated early in the disease process.
19088824 [Overexpression of programmed cell death 5 factor enhances triptolides-induced fibroblast- 2008 Dec 18 OBJECTIVE: To explore the effect of programmed cell death 5(PDCD5) on apoptosis of rheumatoid arthritis fibroblast-like synoviocytes(RA FLS) induced by triptolide. METHODS: Cultured synovial cells in vitro from RA patients were transfected with Ad-PDCD5.At protein level, expression of PDCD5 in RA FLS infected with Ad-PDCD5 was detected by Western blot.RA FLS infected with Ad-PDCD5 were cultured in presence or absence of triptolide and apoptosis of RA FLS was determined by flow cytometry. RESULTS: Infection of RA FLS with increasing concentrations of Ad-PDCD5(50-300 MOI) resulted in a does-dependent increase in the production of PDCD5. Apoptotic cells percentage for noinfection group, Ad-null group and Ad-PDCD5 group were(22.41 +/- 3.87)%, (28.77 +/- 12.97)% and (48.87 +/- 12.69)%, respectively. Alternatively, infection without addition of triptolide stimuli had no effect. The data showed that gene transfection of PDCD5 alone without addition of triptolide was not sufficient to activate RA FLS apoptosis, PDCD5 acted as an enhancer rather than inductor of apoptosis. CONCLUSION: Overexpression of PDCD5 could enhance apoptosis of RA FLS induced by triptolide, PDCD5 may be a potential therapeutic target to RA.
18512775 Dramatic regulation of heparanase activity and angiogenesis gene expression in synovium fr 2008 Jun OBJECTIVE: Although heparanase is recognized as a proangiogenic factor, the involvement of heparanase in rheumatoid arthritis (RA) is unclear. In this study, we assessed heparanase activity in synovial fluid (SF) and synovial tissue (ST) from patients with RA or osteoarthritis (OA), and analyzed the expression of angiogenic pathway-focused genes in ST from RA and OA patients. METHODS: SF and ST were obtained from the knees of patients with either RA or OA and from asymptomatic donors with no documented history of degenerative or inflammatory joint diseases. Heparanase activity was determined by an enzymatic assay using a radiolabeled substrate, and the presence of heparanase in ST was demonstrated by Western blotting. The expression of angiogenesis genes, including heparanase, in ST was analyzed by real-time quantitative polymerase chain reaction. RESULTS: Heparanase activity was dramatically higher (>100-fold) in SF and ST from RA patients than in SF and ST from OA patients and asymptomatic donors. Active heparanase enzyme was detected and heparanase messenger RNA was up-regulated in ST from RA patients. We also found that angiogenesis gene expression was significantly regulated in RA synovium, and was correlated with heparanase activity. CONCLUSION: These findings are novel and contribute to our understanding of joint destruction in RA, suggesting that heparanase may be a reliable prognostic factor for RA progression and an attractive target for the treatment of RA.
18635256 Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept i 2008 Aug 2 BACKGROUND: Remission and radiographic non-progression are goals in the treatment of early rheumatoid arthritis. The aim of the combination of methotrexate and etanercept in active early rheumatoid arthritis (COMET) trial is to compare remission and radiographic non-progression in patients treated with methotrexate monotherapy or with methotrexate plus etanercept. METHODS: 542 outpatients who were methotrexate-naive and had had early moderate-to-severe rheumatoid arthritis for 3-24 months were randomly assigned to receive either methotrexate alone titrated up from 7.5 mg a week to a maximum of 20 mg a week by week 8 or methotrexate (same titration) plus etanercept 50 mg a week. Coprimary endpoints at 52 weeks were remission measured with the disease activity score in 28 joints (DAS28) and radiographic non-progression measured with modified total Sharp score. Treatment was allocated with a computerised randomisation and enrolment system, which masked both participants and carers. Analysis was done by modified intention to treat with last observation carried forward for missing data. This study is registered with ClinicalTrials.gov, number NCT00195494). FINDINGS: 274 participants were randomly assigned to receive combined treatment and 268 methotrexate alone. 132 of 265 (50%, 95% CI 44-56%) patients who took combined treatment and were available for assessment achieved clinical remission compared with 73 of 263 (28%, 23-33%) taking methotrexate alone (effect difference 22.05%, 95%CI 13.96-30.15%, p<0.0001). 487 evaluable patients had severe disease (DAS28>5.1). 196 of 246 (80%, 75-85%) and 135 of 230 (59%, 53-65%), respectively, achieved radiographic non-progression (20.98%, 12.97-29.09%, p<0.0001). Serious adverse events were similar between groups. INTERPRETATION: Both clinical remission and radiographic non-progression are achievable goals in patients with early severe rheumatoid arthritis within 1 year of combined treatment with etanercept plus methotrexate. FUNDING: Wyeth Research.
16435121 Ochronotic arthropathy, an approach to osteoarthritis bone remodelling. 2006 Apr The objective is to use hip ochronotic arthropathy for an indirect approach to osteoarthritis bone remodelling in a human joint via an identified causal chondropathy. The method is via radiology connecting pathology and nosology, based on the study of seven ochronotic femur heads excised in alcaptonuric patients. Due to the brittleness of ochronotic cartilage, bone remodelling similar to that of hip osteoarthritis exists with diffuse narrowing of the interarticular space and (except in one case modified by intermediary surgery) poorly developed osteophytes. Ochronotic arthropathy is only a privileged model of osteoarthritis bone remodelling, the pathology of which might well evidence the stages of the process, with marking by pigmented cartilage remnants Thus it may lead to various reflections in rheumatology, among others concerning the respective radiological hip images of osteoarthritis and rheumatoid arthritis. The use of the pathology-radiology files provided by hip surgery of ochronotic arthropathy might offer a useful reference model for investigating various aspects of osteoarthritis.
18538830 Selective costimulation modulation with abatacept: a look at quality-of-life outcomes in p 2009 Jun OBJECTIVES: To highlight the importance of improving quality of life (QoL) in patients with rheumatoid arthritis (RA) and to provide a summary of the QoL benefits provided by abatacept in patients who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and/or tumor necrosis factor (TNF) antagonists. METHODS: A literature search of the MEDLINE, EMBASE, and BIOSIS databases was performed using the terms "abatacept," "cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)" and "ORENCIA," with the coindexing terms: "abatacept," "CTLA-4," and "ORENCIA." Only articles presenting primary data on QoL outcomes from randomized, placebo-controlled clinical trials of abatacept were included in the review. RESULTS: The literature search initially yielded 220 articles. A total of 8 articles fulfilled the inclusion criteria described above and are reviewed here. In clinical trials to date, abatacept treatment has been shown to improve QoL in patients who have an inadequate response to traditional DMARDs and TNF antagonists. CONCLUSIONS: Improvements in QoL are rated by patients as 1 of the most important benefits of an effective treatment; however, inclusion of QoL measurements in clinical trials as a measure of efficacy is a relatively recent event. Abatacept has been shown to alleviate both the physical and the emotional/social burdens that RA imposes on the patient, including improvements in day-to-day activity and reducing sleep problems and fatigue in patients with RA who have an inadequate response to DMARDs and/or TNF antagonists.
17332704 [Evidence of cartilaginous benefit of treatment with infliximab in rheumatoid arthritis us 2007 Feb Recently, it has become possible to measure the concentration of serum cartilage oligomeric matrix protein (COMP) in various arthritis, and it is expected to be a novel biomarker indicative of cartilage destruction. In this study, we evaluated the diagnostic effectiveness of serum COMP in rheumatic diseases and analyzed the inhibition of cartilage destruction in patients with rheumatoid arthritis who were prescribed with infliximab (IFX) for one year. The changes in the concentration of serum COMP and the joint narrow space of Sharp score (Delta Sharp-JNS) were evaluated. The level of serum COMP decreased from 23.04+/-7.14 U/l to 8.69+/-2.89 U/l (p<0.005) and improved Delta Sharp-JNS (-0.50+/-6.38 points). We believed that these results were influenced by the effects of methotrexate (MTX) that was prescribed together with IFX, and we analyzed the group that was administered only MTX therapy as a reference. However, the serum COMP concentration and Sharp-JNS in the MTX group did not decrease. The serological and radiological results revealed that IFX inhibited cartilage destruction, and it is possible that serum COMP is one of the novel biomarkers in RA patients treated with anti-tumor necrosis factor-alpha antibody therapy.
16521050 A case report of tumor necrosis factor-alpha antibody-induced thrombocytopenia associated 2007 Jun It is commonly believed that infliximab-induced anticardiolipin antibody belongs to the IgM subclass but not the IgG subclass and that the IgM subclass could not produce clinical symptoms. However, we had a patient with scleroderma overlap/rheumatoid arthritis who developed thrombocytopenia associated with the appearance of IgM anticardiolipin antibody after treatment with infliximab. This is a report of a rare case that should make us aware of the possibility of the development of thrombocytopenia with the appearance of IgM anticardiolipin antibody induced by infliximab.
17957370 Diastolic heart function in RA patients. 2008 Apr The results of some epidemiological studies point to the presence of an increased risk of cardiovascular disease (CVD), particularly atherosclerosis and congestive heart failure (CHF) in rheumatoid arthritis (RA). At least 50% of abnormalities remained asymptomatic. Pathological conditions contributing to myocardial dysfunction such as high serum levels of IL-6, C-reactive protein (CRP) and TNF alpha are present both in RA and CHF patients. The most common pathological mechanism leading to the development of heart failure is left ventricular (LV) diastolic dysfunction, which remains clinically asymptomatic for a long time. The aim of this study was to assess the systolic and diastolic functions of the LV in RA patients without clinically evident cardiovascular disease, using pulsed Doppler echocardiography. Our purpose was also to estimate whether there is a correlation between the duration and severity of RA and the degree of LV diastolic dysfunction. A comparison of the average values of echocardiographic measurements was made between the RA group and control group, which constituted healthy volunteers. Left ventricular mass index in RA group was significantly greater than in the control group (105.2 +/- 32.6 vs. 87.9 +/- 16.8; p < 0.05) so were the interventricular septum end-diastolic thickness (1.01 +/- 0.33 vs. 0.86 +/- 0.12; p < 0.05), the LV posterior wall end-diastolic thickness (0.94 +/- 0.08 vs. 0.83 +/- 0.11; p < 0.0001) and the aortic root diameter (3.18 +/- 0.31 vs. 3.10 +/- 0.63, p < 0.001). The ejection fraction in RA group was significantly lower than in the control group (64.4 +/- 1.3 vs. 66.3 +/- 1.3; p < 0.0001). The assessment of diastolic function parameters revealed significantly longer isovolumetrc relaxation time (IVRT) and shorter deceleration time (DT) in RA patients compared to the control group. Patients in stage II or III revealed significantly lower LV mass index (99 +/- 17 vs. 131 +/- 42; p < 0.05) and the interventricular septum end-diastolic thickness (0.94 +/- 0.10 vs. 1.28 +/- 0.5; p < 0.05) than those in stage IV. Mean aortic diameter was significantly greater in individuals in stages III and IV (3.73 +/- 0.28) than in the stage II of the disease (2.77 +/- 0.21), p < 0.05. No differences in echocardiographic parameters' values were observed between seropositive, seronegative, nodule-present and nodule-absent persons. Echocardiographic examination revealed valvular heart disease in 24 (80%) RA and 6 (20%) control patients (p < 0.0001).