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ID PMID Title PublicationDate abstract
18854877 [Fish oil supplementation in rheumatoid arthritis]. 2008 Jul The beneficial properties of fish oil are well known and are related to its fatty acid composition rich in omega-3 polyunsaturated fatty acids. In the last years a variety of epidemiological and clinical studies have demonstrated the efficacy of fish oil supplementation in the rheumatic diseases, in particular in rheumatoid arthritis. The anti-inflammatory effects of fish oil are linked to the production of alternative eicosanoids, to the reduction of proinflammatory cytokines, to the inhibition of the activation of T lymphocytes and of catabolic enzymes. Fish oil supplementation could represent a valuable support to the traditional pharmacological treatment of rheumatoid arthritis.
17786135 [Autoimmune aspects of treatment with TNF-alpha inhibitors]. 2007 Aug 28 Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of such diseases as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and juvenile chronic arthritis. Recent years have brought improvement in the understanding of the pathogeneses of these diseases, resulting in the production of new groups of biological drugs, including, among others, anti-TNF-alpha antibodies. The use of TNF inhibitors has been a great advance in the treatment of patients with these inflammatory diseases. Infliximab and adalimumab are monoclonal antibodies that bind to and neutralize the activity of TNF-alpha. Infliximab is a mouse/human chimera that joins the variable regions of a mouse antibody to the constant region of human IgG1. Adalimumab is a fully human IgG1 antibody. Etanercept is a dimeric fusion protein that joins the human p75 TNF receptor to the Fc domain of human IgG1. The beneficial effects of the anti-TNF monoclonal antibodies infliximab and adalimumab and the soluble receptor fusion protein etanercept in the treatment of rheumatoid arthritis, especially in patients resistant to other disease-modifying antirheumatic drugs (DMARDs), are discussed. We observe stoppage of articular destruction during treatment with TNF-alpha inhibitors. Soon after the introduction of this therapy it was found that these agents have a propensity for stimulating the production of autoantibodies and antibodies against themselves. In this review, recent studies analyzing the effect of TNF-alpha blockade (infliximab, etanercept, and adalimumab) on the ANA, anti-dsDNA, and anticardiolipin antibody profiles in autoimmune diseases are discussed.
16762156 Anti-Clq antibodies in patients with chronic hepatitis C infection. 2006 Mar OBJECTIVE: Extrahepatic autoimmune features of HCV infection include autoantibody production and the development of mixed cryoglobulinemia. Anti-Clq antibody, detected with high frequency in systemic lupus erythematosus and hypocomplementemic urticarial vasculitis, may have a direct pathogenic role in complement mediated autoimmune diseases. In this study, we investigate the prevalence of anti-Clq antibody in a population of patients with chronic HCV infection. METHODS: Serum was obtained from a group of 50 patients with chronic HCV infection and control groups comprised of patients with SLE, rheumatoid arthritis (RA), scleroderma (PSS), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and healthy individuals. RESULTS: Anti-Clq antibody was detected in 38% of HCV patients compared with 2% of healthy controls (p < 0.0001). Levels were also significantly elevated in patients with SLE (61%), RA (20%), PSS (15%), SS (15%) and MCTD (15%). CONCLUSION: In addition to numerous other autoantibodies, patients with chronic HCV infection exhibit increased production of anti-Clq IgG antibodies. This observation may have implications for the pathogenesis of the mixed cryoglobulinemic vasculitis syndrome.
16344625 Musculoskeletal manifestations and autoimmune diseases related to new biologic agents. 2006 Jan PURPOSE OF REVIEW: The anti-tumor necrosis factor agents are now widely used in the management of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile inflammatory arthritis. One of the most common observations made during their use is the development of autoantibodies. The purpose of this paper is to review this phenomenon and its clinical implications. RECENT FINDINGS: While the development of different autoantibodies is a common encounter, rare cases of lupus-like syndromes have been reported. On the other hand, a variety of immune-mediated clinical manifestations have been described, including vasculitis and demyelinating syndromes. Rare cases of cytopenia and non-specific lung injuries have also been reported. SUMMARY: While these clinical complications are rare and isolated events, clinicians must be aware of their occurrence. The experience with the anti-tumor necrosis factor agents is rather short and new, unusual immune-mediated complications may still appear. Clinicians should be prepared to recognize them.
18824600 A key role for G-CSF-induced neutrophil production and trafficking during inflammatory art 2008 Dec 15 We have previously shown that G-CSF-deficient (G-CSF(-/-)) mice are markedly protected from collagen-induced arthritis (CIA), which is the major murine model of rheumatoid arthritis, and now investigate the mechanisms by which G-CSF can promote inflammatory disease. Serum G-CSF levels were significantly elevated during CIA. Reciprocal bone marrow chimeras using G-CSF(-/-), G-CSFR(-/-), and wild-type (WT) mice identified nonhematopoietic cells as the major producers of G-CSF and hematopoietic cells as the major responders to G-CSF during CIA. Protection against CIA was associated with relative neutropenia. Depletion of neutrophils or blockade of the neutrophil adhesion molecule, Mac-1, dramatically attenuated the progression of established CIA in WT mice. Intravital microscopy of the microcirculation showed that both local and systemic administration of G-CSF significantly increased leukocyte trafficking into tissues in vivo. G-CSF-induced trafficking was Mac-1 dependent, and G-CSF up-regulated CD11b expression on neutrophils. Multiphoton microscopy of synovial vessels in the knee joint during CIA revealed significantly fewer adherent Gr-1(+) neutrophils in G-CSF(-/-) mice compared with WT mice. These data confirm a central proinflammatory role for G-CSF in the pathogenesis of inflammatory arthritis, which may be due to the promotion of neutrophil trafficking into inflamed joints, in addition to G-CSF-induced neutrophil production.
16968399 Post-translational modifications of the major linear epitope 169-190aa of Ro60 kDa autoant 2006 Oct Ro60 kDa is a member of the Ro/LaRNP ribonucleoprotein complex and its major linear B cell epitope, corresponding to the region 169-190aa, has been found to be the initial target of the autoimmune response in patients with systemic lupus erythematosus. This sequence contains one serine and two arginine amino acid residues, which can potentially be modified post-translationally by phosphorylation or citrullination, respectively. The aim of this study was to develop an immunoassay for anti-Ro60 kDa epitope antibody detection and to investigate the changes in the antigenicity of the Ro60 kDa epitope when it is post-translationally modified, by either citrullination or phosphorylation. Peptide analogues corresponding to the unmodified form of the epitope, its phosphorylated form, and a form with both arginine residues citrullinated were synthesized. The peptide coating conditions were investigated and it was found that the use of highly hydrophilic surfaces increase the efficiency of the coating, as well as the sensitivity of the method for anti-peptide antibody detection. All peptides were tested by the optimized enzyme-linked immunosorbent assay (ELISA) against 119 sera from patients with primary Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis with anti-Ro/SSA reactivity, 20 sera from patients with systemic diseases without anti-Ro/SSA immune reactivity, as well as against 65 sera from normal individuals. A large proportion of the tested sera reacted against all three peptide analogues, although with a preference for the unmodified form of the epitope. In conclusion, post-translational modifications of the major Ro60 kDa B cell epitope can alter the autoantibody binding.
16535926 [Modifications of markers of bone resorption in patients affected by glucocorticoid induce 2006 Jan Almost 30-50% of patients on long-term therapy with glucocorticoids (GC), especially those affected by rheumatic diseases, develop glucocorticoid induced osteoporosis (GIOP) and osteoporosis-related fractures. To assess the effects of neridronate versus placebo on markers of bone resorption in rheumatic patients affected by GIOP (as defined by a T Score reduction > 2.5; mean BMD L2-L4), sixty-two female patients [age: 68.89 +/- 9.45 (mean +/- SD)] affected by different rheumatic diseases, like rheumatoid arthritis, polymyalgia rheumatica, Sjögren syndrome in treatment with a mean prednisone-equivalent daily dose of 6.44 +/- 2.4 mg/day, were enrolled in an open trial. The patients were divided in 2 groups: group A (26 patients) assuming daily calcium 1 g and vitamin D 800 UI and group B (36 patients) assuming daily calcium (1000 mg) and vitamin D (800 UI) and neridronate (25 mg im /30 days). The patients were evaluated for serum and urinary bone markers, basely (T0) and after 6 months of therapy (T6). After 6 months of therapy (T6), bone markers were significantly reduced in group B in respect to group A: OHPr - 41.64% (p < 0.001), D-Pyr - 34.96% (p < 0.001), NTX - 50.9% (p < 0.001). These preliminary data show that neridronate may be considered an useful agent for the treatment of GIOP in rheumatic patients.
17033165 Anti-tumor necrosis factor alpha-induced psoriasiform eruptions: three further cases and c 2006 The increasing use of anti-TNF-alpha agents led to a better knowledge of their side effects. Among the cutaneous reactions, psoriasiform eruptions are increasingly described. We encountered 3 further psoriasiform eruptions during anti-TNF-alpha treatment for rheumatologic conditions and review the literature in order to identify the common characteristics of these cases. We found 30 case reports by using a comprehensive search of the 1966-2005 Medline database with a wild variety concerning the psoriasis type of eruption, the anti-TNF-alpha agent, the treatment duration and the presence or absence of a personal or familial history of psoriasis. We conclude that a psoriasiform eruption during anti-TNF-alpha treatment seems to be a class effect, without any as yet known identified predisposing factors, but it is more often self-limited and does not require treatment discontinuation.
18050387 Requirement of methotrexate in combination with anti-tumor necrosis factor-alpha therapy f 2007 Dec OBJECTIVE: To determine that concomitant use of methotrexate (MTX) is required to achieve adequate suppression of bone destruction in treating rheumatoid arthritis (RA) with tumor necrosis factor-alpha (TNF-alpha)-inhibiting biologic therapy. We quantitatively compared the suppressive effects of treatment with a combination of infliximab and MTX and treatment with each of these 2 agents alone on bone destruction in SCID-HuRAg-pit mice. METHODS: Tissue derived from human RA pannus was implanted with a slice of dentin subcutaneously in the backs of SCID mice (SCID-HuRAg-pit model). Infliximab was administered daily to SCID-HuRAg-pit mice using an osmotic pump for 2 weeks with or without oral administration of MTX. Histological changes in tissue and the pits formed on the dentin slice were examined 8 weeks after transplant. Serum concentrations of TNF-alpha and interleukin 6 (IL-6) were also measured. RESULTS: Treatment with a combination of infliximab and MTX suppressed pit formation significantly, while treatment with neither infliximab alone nor MTX alone had a significant effect on pit formation. Synovial inflammation and serum TNF-alpha and IL-6 levels were suppressed by infliximab with or without MTX. CONCLUSION: This is the first evidence in an animal model of arthritis that concomitant use of MTX is required to achieve adequate suppression of bone destruction when treating RA with a TNF-alpha-inhibiting biologic. Our findings suggest that infliximab suppresses bone destruction through a mechanism of action different from that mediating its antiinflammatory effects in the treatment of RA.
16977613 Transdermal photodynamic therapy--a treatment option for rheumatic destruction of small jo 2006 Oct BACKGROUND AND OBJECTIVE: Synovectomy of small joints is a therapeutic approach in patients suffering from rheumatoid arthritis (RA). We examined the feasibility of transdermal photodynamic therapy (tPDT) in a fibroblast-induced model of joint destruction using the novel photosensitizer (PS) tetrahydroporphyrin-tetratosylat that shows strong absorption at the near infra-red spectral region. MATERIALS AND METHODS: The functionality of the PDT system was assessed in vitro. Following arthritis induction and PS application, tPDT was applied in vivo. Therapy results were evaluated by measuring joint swelling, serum amyloid A (SAA) and histologically. RESULTS: We were able to present a fully functional PDT in vitro. The in vivo therapy modalities were well tolerated by mice. We could demonstrate photodynamic ablation of subcutaneously located tissue (skeletal muscle) without skin damage. CONCLUSION: This study provides the basis for transdermal accessibility of tissue through a photodynamic process which may serve as a minimally invasive synovectomy strategy.
18061135 Immunologic markers as potential predictors of systemic autoimmune disease in patients wit 2008 Mar PURPOSE: To determine the clinical value of serological testing in patients with idiopathic scleritis. DESIGN: Retrospective case series. METHODS: Medical records of patients with scleritis seen at an institutional referral center over an 11-year period were reviewed. RESULTS: Of 119 patients with scleritis seen at the University of Illinois Uveitis Clinic, 91 (76.5%) patients had no known etiology at initial presentation. Seventy of the 91 patients were tested for rheumatoid factor (RF), 19 (27.1%) of whom had a positive result. Ten (52.6%) of these RF positive patients were subsequently diagnosed with rheumatoid arthritis (RA) during a mean follow-up of 10.6 months (range, zero to 72 months), whereas only one of 51 (2.0%) RF negative patients developed RA, producing an odds ratio for developing RA in RF positive patients of 55.6 (95% confidence interval (CI) 7.8 to 369.8, P=.00001). Of the 70 patients who were tested for anti-neutrophil cytoplasmic antibody (ANCA), seven (10.0%) tested positive. Three (42.9%) of the ANCA positive patients subsequently developed Wegener granulomatosis (WG), whereas only two of 63 ANCA negative patients (3.2%) developed WG during a mean follow-up of 8.4 months (range, zero to 72 months). The odds ratio for developing WG in patients with idiopathic scleritis and a positive ANCA screen compared with a negative ANCA was 22.9 (95% CI 3.4 to 154.2, P=.006). CONCLUSIONS: The likelihood of patients with idiopathic scleritis developing RA and WG was increased if they had a positive RF or ANCA, supporting the role of immunologic marker testing in patients who present without systemic disease.
17082220 Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear 2006 Aug 31 We have comprehensively identified the genes whose expressions are augmented in bone marrow-derived mononuclear cells (BMMC) from patients with Rheumatoid Arthritis (RA) as compared with BMMCs from Osteoarthritis (OA) patients, and named them AURA after augmented in RA. Both stepwise subtractive hybridization and microarray analyses were used to identify AURA genes, which were confirmed by northern blot analysis and/or reverse transcription polymerase chain reaction (RT-PCR). We also assessed their expression levels in individual patients by quantitative real-time RT-PCR. Of 103 AURA genes we have identified, the mRNA levels of the following 10 genes, which are somehow related to immune responses, were increased in many of the RA patients: AREG (=AURA9), FK506-binding protein 5 (FKBP5 = AURA45), C-type lectin superfamily member 9 (CLECSF9 = AURA24), tyrosylprotein sulfotransferase 1 (TPST1 = AURA52), lymphocyte G0/G1 switch gene (G0S2 = AURA8), chemokine receptor 4 (CXCR4 = AURA86), nuclear factor-kappa B (NF-kappaB = AURA25) and two genes of unknown function (FLJ11106 = AURA1, BC022398 = AURA2 and XM_058513 = AURA17). Since AREG was most significantly increased in many of the RA patients, we subjected it to further analysis and found that AREG-epidermal growth factor receptor signaling is highly activated in synovial cells isolated from RA patients, but not in OA synoviocytes. We propose that the expression profiling of these AURA genes may improve our understanding of the pathogenesis of RA.
18187046 The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism 2008 Mar The production of a variety of lipid mediators is enhanced in bone-resorptive diseases such as osteoporosis, rheumatoid arthritis, osteoarthritis, and periodontitis. Prostaglandin E(2) (PGE(2)) is one of the most notable lipid mediators of bone remodeling, and has been linked clinically to many bone-resorptive diseases. In vitro studies with bone cell cultures have demonstrated that the bone-resorptive activity of PGE(2), which is mediated by receptor activator of NF-kappaB ligand (RANKL), is key for the induction of osteoclast formation. Furthermore, interleukin (IL)-1- and IL-6-stimulated bone resorption involves PGE(2) production. In addition to its bone-resorptive effects, PGE(2) promotes bone formation in vitro by stimulating osteoblastic proliferation and differentiation. The multifaceted nature of PGE(2) makes it difficult to discern its role during bone remodeling. Leukotrienes (LTs), and particularly LTB(4), have also been implicated in bone remodeling and disease-specifically in rheumatoid arthritis. Moreover, recent studies from our laboratory have shown that platelet-activating factor (PAF) receptor-deficient mice develop only mild osteoporosis. Osteoclast survival in these mice is shortened and osteoclastic bone resorption is impaired. This review article focuses on these families of lipids and their function during bone metabolism and disease.
16874798 Assessment of coxib utilization by rheumatologists for nonsteroidal antiinflammatory drug 2006 Aug 15 OBJECTIVE: To examine cyclooxygenase 2 inhibitor (coxib) utilization by rheumatologists for patients receiving nonsteroidal antiinflammatory drugs (NSAIDs) prior to the coxib market withdrawals. METHODS: A prospective study of patients with rheumatoid arthritis enrolled in the Consortium of Rheumatology Researchers of North America registry was performed. RESULTS: Of 1,833 patients receiving prescription NSAIDs, 1,380 (75.3%) received gastroprotection, defined as either coxib monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs. The distribution of gastroprotective strategies included 860 (46.9%) patients who were prescribed coxib monotherapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAID (NS-NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS-NSAID without GPA cotherapy. For patients with 0, 1, and > or =2 identifiable gastrointestinal (GI) risk factors, coxib prescribing rates as a proportion of NSAID agents were 64.1%, 66.4%, and 68.6%, respectively; among dual aspirin/NSAID users, coxib prescribing rates were 66.2%, 78.3%, and 68.5% of NSAID prescriptions, respectively. CONCLUSION: The majority of NSAID users were prescribed a gastroprotective strategy, primarily attributable to coxib utilization. Coxib utilization rates were consistently high across all levels of GI risk, including patients without identifiable risk factors. These data indicate that rheumatologists broadly adopted the coxib class of NSAIDs in a nonselective manner with respect to underlying GI risk and concomitant aspirin use. As novel therapeutic classes are introduced, early evaluation of prescribing patterns using arthritis registries can determine the appropriateness of prescribing patterns and may improve patient outcomes.
16644022 Inhibitors of kB-like gene polymorphisms in rheumatoid arthritis. 2006 Jun 15 OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G, and -62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421 was significantly different between DR4(+) RA patients and DR4(+) controls (p = 0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+) RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4-147.0). We also found that the allele frequency of IkBL -62 T was significantly higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1). The allele carriage frequency of IkBL -62 T tended to be increased in RA patients (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL -421 8T/-62 T tended to be increased in RA patients compared with controls (p = 0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated with the development of RA in Taiwan. The IkBL -421 8T may also be related to susceptibility to RA in HLA-DR4(+) individuals. This study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to RA in Taiwan.
19120158 Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis 2008 Dec Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.
17284392 [Therapeutic maintenance level of methotrexate in rheumatoid arthritis]. 2006 Jul OBJECTIVES: To determine the probability of drug continuation, the reasons for discontinuation of methotrexate (MTX), and risk factors of treatment termination in rheumatoid arthritis. MATERIALS AND METHODS: Retrospective cohort study of a 100 case follow-up between 1983 and 2003, all treated with MTX. Factors associated with toxicity, and efficacy of MTX were studied. Logistic regression was used to study the relation between baseline variables and various dependent factors. RESULTS: Eighty three women and seventeen men were included in this study. The mean age at commencement of MTX was 45+/-13.7 (18-81) years. The mean duration of disease was 9.5+/-8.7 (0.25-40) years. The mean weekly dose of MTX was 9.8+/-3.4 mg/week. The therapeutic maintenance level of MTX was 76% at one year, 63% at 2 years and 45% at 5 years. The median of treatment duration was 10 (0. 5-40) months. Reasons for patients stopping MTX were: Adverse effects (15), lack of effect (1), non medical reasons (14) essentially because of financial difficulties. Baseline white blood cell counts >9 giga/mm3 (RR: 3.17) [95 %:1.03-9.74] (p=0.04) and baseline serum creatinine level >72 micromol/L (RR: 8.6) [95 %:1.04-71.17] (p=0.04) were associated with an increased risk of treatment termination. CONCLUSION: The continuation rate of methotrexate in our study was good, despite the poor compliance with the treatment due to financial difficulties.
17985409 Effectiveness, predictive response factors, and safety of anti-tumor necrosis factor (TNF) 2007 Dec OBJECTIVE: To evaluate the effectiveness and safety of anti-tumor necrosis factor (anti-TNF) therapies in rheumatoid arthritis (RA), and to identify the factors involved in this response. METHODS: Dynamic prospective cohort study of patients with RA treated with anti-TNF under clinical practice conditions. Effectiveness was evaluated using Disease Activity Score (DAS) 28, European League Against Rheumatism (EULAR) response, Health Assessment Questionnaire (HAQ), and time to treatment failure. Prior adherence was evaluated retrospectively and safety was evaluated by adverse events (AE). The analysis was restricted to anti-TNF-naive patients. RESULTS: The study included 161 patients treated for RA during 6 years (60 infliximab, 79 etanercept, and 22 adalimumab). At 6 months, 15% reached a good EULAR response and 38% a moderate response. A mean decrease of -1.5 (p < 0.0001) was observed in the DAS28 and of -0.34 in the HAQ (p < 0.0001); however, women showed poorer progress in terms of DAS and HAQ. In the first year, 64.3% did not experience treatment failure and this figure was 50.5% after 2 years. In one-third, glucocorticoids were withdrawn and in the remainder the dose was reduced by 50%. Adherence to treatment, selection of etanercept, and intensification of infliximab were associated with a lower probability of premature failure in the multivariate model. AE were similar to other those in studies and no outstanding differences in safety were found between the 3 anti-TNF therapies. CONCLUSIONS: Anti-TNF treatments are effective and safe, reducing the activity of the disease, disability, and the need for corticosteroids. Patients who displayed good adherence prior to the anti-TNF treatment and were treated with etanercept or with increasing doses of infliximab had the best chance of displaying a response.
16914096 Altered production of IFN-gamma? And other inflammation-related cytokines by mycobacteria- 2006 May 15 Peripheral blood mononuclear cells taken from 32 patients with Rheumatoid Arthritis (RA) receiving neither steroids nor methotrexate and 34 healthy controls were examined for lymphoproliferation in the presence of ultrasonic extracts of 14 different mycobacterial species or serotypes, of an extract of Candida albicans and of 2 mitogens. Additionally, cells were incubated for 96 hours alone, or with Mycobacterium tuberculosis (M.tb) sonicate or Concanavalin-A (Con-A), and supernatants were tested for a range of cytokines. Lymphocytes of rheumatoid patients were less reactive than controls to all the mycobacterial preparations, but no different in their responses to mitogens. Stimulation of patients' cells with M.tb sonicate induced significantly less interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) but more transforming growth factor- beta (TGF-beta) than controls. Even stimulation with Con-A induced much less IFN-gamma in patient's cells than in those of controls. The combination of reduced responses to the mycobacterial reagents and reduced stimulation of type 1 cytokines by the sonicate of M.tb, suggests reduced responsiveness to group i, common mycobacterial antigens. Such findings need not indicate involvement of mycobacteria specifically in the disease aetiology, but provide novel information on the immunopathological abnormalities, which may explain the reported increased susceptibility to mycobacteria of RA patients.
16678642 A comparison of valdecoxib and naproxen in the treatment of rheumatoid arthritis symptoms. 2006 Feb OBJECTIVES: The primary aim of this work was to compare the efficacy of valdecoxib 10, 20, and 40 mg QD with that of placebo and naproxen 500 mg BID in patients with rheumatoid arthritis (RA). The overall safety and tolerability profiles of valdecoxib and naproxen were also compared. METHODS: A 12-week, multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled study was performed in patients with adult-onset RA whose disease was in a flare state after discontinuing NSAIDs or other analgesics. Patients were randomly assigned to valdecoxib 10, 20, or 40 mg QD, naproxen 500 mg BID, or placebo. The primary efficacy measures were the American College of Rheumatology (ACR) 20% responder index (ACR-20), physicians' assessments of tender/painful joint count and swollen joint count, and patients' and physicians' global assessments of disease activity. Adverse events, clinical laboratory data, and vital signs were assessed by the investigator and compared between treatment groups to evaluate overall tolerability and safety. RESULTS: A total of 1093 patients were randomized to receive either valdecoxib 10 mg QD (n=226), valdecoxib 20 mg QD (n=219), valdecoxib 40 mg QD (n=209), naproxen 500 mg BID (n=219), or placebo (n=220). At all time points, the proportion of ACR-20 responders was significantly higher in the valdecoxib groups than the placebo group at weeks 2 (10 mg, P<0.001; 20 mg, P=0.008; 40 mg, P= 0.004), 6 (all, P<0.001), and 12 (10 mg, P=0.006; 20 mg, P=0.004; 40 mg, P<0.001). Similarly, at all time points, the proportion of ACR-20 responders was significantly higher in the naproxen 500-mg group than the placebo group (all time points, P<0.001). In addition, mean changes in the number of tender/painful joint counts were significantly greater in the valdecoxib groups than the placebo group at weeks 2 (all, P<0.001), 6 (10 mg, P=0.002; 20 and 40 mg, P<0.001), and 12 (10 mg, P=0.004; 20 mg, P= 0.012; 40 mg, P<0.001). Naproxen treatment was also associated with greater reductions in tender/painful joint count than placebo (all, P<0.001). Mean changes in swollen joint count decreased at all time points in all groups, with significantly greater changes in the valdecoxib and naproxen treatment groups than the placebo group (valdecoxib 20 and 40 mg: week 6, P= 0.014 and P=0.003, respectively; naproxen: week 2, P=0.014; week 6, P=0.015; week 12, P=0.030). Physicians' global assessments of disease activity scores were significantly lower in the valdecoxib (10 mg: weeks 2 and 6, P<0.001; week 12, P=0.001; 20 and 40 mg: all weeks, P<0.001) and naproxen (all time points, P<0.001) treatment groups than the placebo group. Adverse events were reported by 45.5% patients in the placebo group, 51.8% in the valdecoxib 10 mg QD group, 58.0% in the valdecoxib 20 mg QD group, 56.9% in the valdecoxib 40 mg QD group, and 62.6% in the naproxen 500 mg BID treatment group. CONCLUSIONS: Valdecoxib 10, 20, and 40 mg QD were efficacious for treating the signs and symptoms of RA in these patients. The efficacy of valdecoxib 20 and 40 mg QD was not significantly different from that of naproxen 500 mg BID. Valdecoxib was generally well tolerated in this study.