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ID PMID Title PublicationDate abstract
18079191 The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic 2008 May OBJECTIVE: The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of >200 mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients suggests that treatment with anti-TNF-alpha therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.
16278818 Synovial fluid macrophages are capable of osteoclast formation and resorption. 2006 Jan To determine whether synovial fluid (SF) macrophages isolated from the SF of osteoarthritis (OA), rheumatoid arthritis (RA) and pyrophosphate arthropathy (PPA) joints are capable of osteoclast formation, and to investigate the cellular and humoral factors required for this to occur, SF macrophages (CD14+) were isolated from the knee joint SF from patients with OA, RA and PPA and cultured for up to 14 days with macrophage-colony stimulating factor (M-CSF) and soluble receptor activator for nuclear factor-kappaB ligand (RANKL) or tumour-necrosis factor-alpha (TNFalpha) and interleukin-1alpha (IL-1alpha). Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR), F-actin ring formation and lacunar resorption. Osteoclast formation and lacunar resorption was seen in RANKL-treated cultures of SF macrophages isolated from OA, RA and PPA joints with the largest amount of resorption noted in RA and PPA SF macrophage cultures. In TNFalpha/IL-1alpha-treated RA and PPA SF macrophage cultures, osteoclasts capable of lacunar resorption were also formed. Lacunar resorption was more extensive in RANKL than TNFalpha/IL-1alpha-treated cultures. These findings indicate that SF macrophages are capable of differentiating into mature osteoclasts capable of lacunar resorption. M-CSF in combination with RANKL or TNFalpha/IL-1alpha was required for osteoclast formation. As inflammatory synovial fluids contain an increase in the number of macrophages and an increase in the amounts of RANKL, TNFalpha and IL-1alpha, these findings suggest that one means whereby bone erosions may form in rheumatoid or crystal arthritis is by differentiation of synovial fluid macrophages into osteoclasts.
17827929 Comparative studies on effect of risedronate and alfacalcidol against glucocorticoid-induc 2007 Sep Osteoporosis is a common adverse reaction induced by glucocorticoid treatment. Bisphosphonate, vitamin D(3) (VD(3)) or vitamin K(2) (VK(2)) is recommended as first or second choice of drug for treatment of glucocorticoid-induced osteoporosis. In the present study, the treatment effect of risedronate against glucocorticoid-induced osteoporosis in rheumatoid arthritic patients was compared with that of alfacalcidol. Twelve patients were randomized to receive either risedronate (2.5 mg) or alfacalcidol (0.5 microg) daily for 48 weeks. Each patient also received 800 mg of calcium supplementation (800 mg/day) daily. Bone mineral density (BMD) and the biochemical markers of bone turnover were measured before (baseline) and 12, 24, and 48 weeks after treatment with risedronate or alfacalcidol, and the percentage changes in these parameters from baseline were compared. The BMD values 12, 24 and 48 weeks after treatment with risedronate increased by 3.9%, 4.1% and 5.2%, respectively, which were significantly higher than those after treatment with alfacalcidol (2.8%, 2.1% and 2.5%, respectively). Urinary excretion of N-telopeptides of type I collagen and deoxypyridinoline after risedronate treatment were more significantly decreased than that after alfacalcidol treatment. The present findings at least suggest that risedronate is more useful for the prevention and treatment of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis than alfacalcidol, although the number of patients studied was small.
17480140 Radioactive pain relief: health care strategies and risk assessment among elderly persons 2007 Apr OBJECTIVES: The aim of this study was to examine the use of radioactive radon therapy among persons with arthritis, and to explore their perceptions of risk versus benefit in using this therapy. DESIGN: This was a qualitative study based on loosely-structured and open-ended interviews, which were then analyzed for themes and patterns. SETTING: Participants in the study were recruited over a period of 5 years from clients of a radon health mine in southwestern Montana. RESULTS: Sixty-two mine clients were interviewed, consisting of 36 women and 26 men, ranging in age from 60 to 92 years. Participants believed that radon therapy was an acceptable choice of treatment for arthritis. Perceived benefits of such therapy included more effective pain relief, avoidance of medication side-effects, lower cost, and increased quality of life. The possible future risk of lung cancer from radon exposure was seen as minimal when compared to the perceived benefits. CONCLUSIONS: Fear about radon and its possible health risks seemed to have little influence on the decision-making process for the study subjects.
16575713 [Evaluation of the Extra Short Musculoskeletal Function Assessment questionnaire XSMFA-D i 2006 Apr AIM: The present study had the objective of evaluating the psychometric characteristics of the shortened 16-item version of the German Short Musculoskeletal Function Assessment questionnaire (XSMFA-D), which was designed for routine assessment of functional capacity in patients with various orthopaedic disorders treated either surgically or medically. METHODS: A total of 382 patients from seven different samples with either osteoarthritis of the knee, osteoarthritis of the hip, rheumatoid arthritis or rotator cuff tear treated either in surgical hospitals or rehabilitation settings were assessed both before and after treatment. The XSMFA-D was compared with both questionnaires measuring similar constructs and widely accepted indicators of health status in musculoskeletal disorders. Psychometric characteristics were computed. RESULTS: The internal consistency (Cronbach's alpha) exceeded 0.90 in most cases for the function index and was between 0.80 and 0.90 in most cases for the bother index of the XSMFA-D. Retest-reliability was between 0.80 and 0.95 for the function index and between 0.60 and 0.92 for the bother index. Correlations between the XSMFA-D subscales and the other questionnaires were substantial, showing construct validity. Criterion validity was also demonstrated as significant relationships with accepted external parameters such as function tests, judgements by physicians, pain self-ratings by patients and disease severity scores were found. Sensitivity to change was as high as for the other assessment instruments used in this study. CONCLUSIONS: The XSMFA-D, a very short assessment instrument, proved to be practical, reliable, valid and sensitive to change among the various patient samples studied. It may be recommended for the assessment of patients' state as well as the evaluation of treatments.
18818868 Miller-Fisher syndrome in a patient with rheumatoid arthritis treated with adalimumab. 2009 Jan Adalimumab is a frequently prescribed TNFalpha inhibitor for treatment of rheumatoid arthritis. We report on a patient who probably developed a Miller-Fisher syndrome after the second injection of adalimumab.
18389289 Relationship between the morphology of the atlanto-occipital joint and the radiographic re 2008 Jun The upper cervical spine is a common focus of destruction from rheumatoid arthritis (RA). Atlanto-axial subluxation (AAS) presents with marked frequency among patients with instability. However, there are occasional patients who show no motion between the occipital bone and atlas on a dynamic cervical radiograph in AAS patients. This study investigated the morphology of the atlanto-occipital joint (AOJ) in AAS patients due to RA using computed tomography, and examined the relationship between its morphology and other radiographic results. Twenty-six consecutive patients with AAS due to RA treated by surgery were reviewed. The subjects included 18 females and 8 males. The average patient age was 59.3 years. The mean duration of RA was 14.3 years. In all the patients, the AOJ was morphologically evaluated using sagittal reconstruction view on computed tomography before surgery. Moreover, the ADI value was investigated at the neutral and maximal flexion position, and atlanto-axial angle (AAA) at the neutral position in preoperative lateral cervical radiographs. The morphology of the AOJ on a CT sagittal reconstruction view was classified into three types as follows: a normal type which showed a maintenance of the joint space, a narrow type which showed a disappearance of the joint space and a fused type which showed the fusion of the AOJ. The pre-operative CT sagittal reconstruction image of the AOJ demonstrated a normal type bilaterally in six cases (Group A). In 15 cases (Group B), CT image demonstrated narrowing on at least one side of the AOJ. In five cases (Group C), CT images demonstrated fusion on at least one side of the AOJ. The average ADI value at the flexion position was 10.7 mm in Group A, 11.7 mm in Group B, and 12.6 mm in Group C. There was no significant difference among those groups. The average ADI value at the neutral position before surgery was 2.8 mm in Group A, 5.9 mm in Group B, and 10.4 mm in Group C. There was no significant difference between Group A and B (P > 0.105), and Groups B and C (P > 0.032), however, there was a significant difference between Groups A and C (P < 0.004). The average AAA value was 25.3 degrees in Group A, 19.3 degrees in Group B and 3.4 degrees in Group C. There was no significant difference between Groups A and B (P > 0.230), however, there was a significant difference between Groups A and C (P < 0.002), and Groups B and C (P < 0.007). This study showed that fusion or ankylosis of the AOJ induced an enlargement of the ADI and anterior inclination of the atlas in the neutral position, despite the fact that normal findings of AOJ showed a slight displacement of the atlas to axis in RA patients showing AAS involvement. This morphology may progress to SAS and VS due to AOJ after atlanto-axial arthrodesis.
16645969 The effect of therapeutic glucocorticoids on the adrenal response in a randomized controll 2006 May OBJECTIVE: To measure the effect of low-dose systemic glucocorticoid treatment on the adrenal response to adrenocorticotropic hormone (ACTH) in patients with rheumatoid arthritis (RA). METHODS: Patients with RA who took part in a randomized double-blind placebo-controlled trial of budesonide (3 mg/day and 9 mg/day) and prednisolone (7.5 mg/day) underwent a short (60-minute) test with injection of ACTH (tetracosactide hexaacetate) at baseline and the day after completing the 3-month treatment program. Plasma cortisol measurements at baseline and 3 months were compared within and between the treatment groups. Individual patients were classified as normal responders to ACTH or as abnormal responders if changes were >2 SD below the pretreatment value in the entire group of study patients. RESULTS: Short tests with ACTH injection were performed on 139 patients before beginning the study medication and on 134 patients after cessation of the medication. There were no changes in the placebo group. Mean plasma cortisol levels following treatment were reduced in all active treatment groups. In addition, mean values were significantly reduced for the 30-minute and 60-minute responses to ACTH. The maximum reduction (35%) occurred in the prednisolone group at 60 minutes. Following treatment, 34% of patients taking budesonide 9 mg and 46% of those taking prednisolone 7.5 mg failed to reach the normal maximum cortisol response to ACTH. Four patients failed to achieve the normal percentage increase in cortisol levels, but only 1 patient failed to meet both criteria. CONCLUSION: Low doses of a glucocorticoid resulted in depression of baseline and ACTH-stimulated cortisol levels after 12 weeks of therapy. Although the responsiveness of the hypothalamic-pituitary-adrenal axis in individual patients generally remained within the normal range, these changes should be investigated further.
16531560 It takes nerve to tell T and B cells what to do. 2006 Jun The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through the peripheral nervous system to regulate the level of immune cell activity and the subsequent magnitude of an immune response. In this review, we will focus our presentation and discussion on the findings that indicate a regulatory role for the peripheral sympathetic nervous system in modulating the level of cytokine and antibody produced during an immune response. Data will be discussed from studies involving the stimulation of the beta2 adrenergic receptor expressed on CD4+ T cells and B cells by norepinephrine or selective agonists. We will also discuss how dysregulation of this line of communication between the nervous and immune systems might contribute to disease development and progression.
19013763 Poor reporting of search strategy and conflict of interest in over 250 narrative and syste 2009 Feb OBJECTIVE: To evaluate the quality of reviews about etanercept (ETN) and infliximab (IFX), two biologic treatments for rheumatoid arthritis (RA). STUDY DESIGN: A comprehensive, systematic review, including searches of MEDLINE, EMBASE, and other electronic databases and hand-searches for published and unpublished literature. Two raters independently examined each article and identified systematic reviews as those including either a description of: (1) sources for identification and data retrieval; or (2) search strategy. They applied the quality of reporting of meta-analyses (QUOROM) instrument to systematic reviews. RESULTS: Of 3,620 total citations, 281 were identified as reviews. Of these, 26 (9%) qualified as systematic rather than narrative. Overall, few reviews described selection of sources, critical appraisal, or quantitative summary or synthesis. Systematic reviews most often failed to explain validity assessment. Several articles did not disclose authors' participation in industry-funded clinical trials. Most reviews published in high impact factor and rheumatology journals did not meet many quality standards. Significant associations existed between review type (narrative vs. systematic) and reported funding (P=0.05), conflicts of interest (P=0.005), and country of publication (P<0.0001). CONCLUSION: More than 90% of the published reviews were narrative and did not report methods and conflicts of interest in sufficient detail, raising concerns about selection and reporting bias.
18576313 Duffy antigen receptor for chemokines and CXCL5 are essential for the recruitment of neutr 2008 Jul OBJECTIVE: The role of chemokines and their transporters in rheumatoid arthritis (RA) is poorly described. Evidence suggests that CXCL5 plays an important role, because it is abundant in RA tissue, and its neutralization moderates joint damage in animal models of arthritis. Expression of the chemokine transporter Duffy antigen receptor for chemokines (DARC) is also up-regulated in early RA. The aim of this study was to investigate the role of CXCL5 and DARC in regulating neutrophil recruitment, using an in vitro model of RA synovium. METHODS: To model RA synovium, RA synovial fibroblasts (RASFs) were cocultured with endothelial cells (ECs) for 24 hours. Gene expression in cocultured cells was investigated using TaqMan gene arrays. The roles of CXCL5 and DARC were determined by incorporating cocultures into a flow-based adhesion assay, in which their function was demonstrated by blocking neutrophil recruitment with neutralizing reagents. RESULTS: EC-RASF coculture induced chemokine expression in both cell types. Although the expression of CXC chemokines was modestly up-regulated in ECs, the expression of CXCL1, CXCL5, and CXCL8 was greatly increased in RASFs. RASFs also promoted the recruitment of flowing neutrophils to ECs. Anti-CXCL5 antibody abolished neutrophil recruitment by neutralizing CXCL5 expressed on ECs or when used to immunodeplete coculture-conditioned medium. DARC was also induced on ECs by coculture, and anti-Fy6 antibody or small interfering RNA targeting of DARC expression effectively abolished neutrophil recruitment. CONCLUSION: This study is the first to demonstrate, in a model of human disease, that the function of DARC is essential for editing the chemokine signals presented by ECs and for promoting unwanted leukocyte recruitment.
16720219 Direct determination of single nucleotide polymorphism haplotype of NFKBIL1 promoter polym 2006 Apr We previously revealed that one of the human leukocyte antigen-linked susceptibility genes for Takayasu's arteritis (TA) was mapped between TNFA and MICB loci and that -63T allele of NFKBIL1, which is between TNFA and MICB loci, was associated with rheumatoid arthritis (RA) in the Japanese population. We have developed a novel typing method based on reference strand-mediated conformation analysis for the upstream sequence of the NFKBIL1 gene, where -422 (T)8/(T)9, -325 C/G, -263 A/G, and -63 T/A polymorphisms were found. Upon the analysis of the patients with TA (n = 84), those with RA (n = 120), and healthy control subjects (n = 217), five common haplotypes named IKBLp*01 through IKBLp*05 were found in the Japanese population. The frequency of IKBLp*03 was significantly increased in the patient with TA (57.1% vs 35.0%, giving an odds ratio of 2.47). In addition, the frequency of IKBLp*01, but not that of other -63T-bearing alleles, was increased in the patients with RA (73.3% vs 58.1%, giving an odds ratio of 1.99), suggesting that the susceptibility to RA was conferred not by -63T alone but by combination of single nucleotide polymorphisms in the NFKBIL1 promoter. A higher promoter activity associated with IKBLp*03 and a lower activity associated with IKBLp*01 may contribute to the susceptibility to TA and RA, respectively.
16607625 The v-MFG test: investigating maternal, offspring and maternal-fetal genetic incompatibili 2006 May The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.
16602610 Fatal pulmonary Mycobacterium abscessus infection in a patient using etanercept. 2006 Jan A case of fatal pulmonary Mycobacterium abscessus infection in a 56-year-old man is reported. The patient had a longstanding history of seropositive, nodular rheumatoid arthritis with severe joint manifestations that had been treated with a regimen of prednisone, leflunomide, and etanercept. He presented to our facility with complaint of productive cough, persistent fevers, pleuritic chest discomfort, and dyspnea at rest. The patient was admitted to hospital, placed in isolation, a left-sided chest tube was inserted (left pneumothorax identified), and sputum acid-fast bacteria stains and cultures were obtained. Fluorochrome stains demonstrated numerous acid-fast bacteria, and M. abscessus was recovered from the culture media. He was treated with a regimen of amikacin, cefoxitin, and clarithromycin. He initially responded well, and was discharged home with this regimen. He remained afebrile with decreased cough and sputum production until 15 days after discharge when he was again admitted to hospital, with acute onset dyspnea and right-sided chest discomfort (right pneumothorax identified). He ultimately expired, due to overwhelming pulmonary infection, 20 days after readmission to hospital. Autopsy revealed acid fast bacilli in the setting of numerous, bilateral, necrotic, granulomatous, cavitary pulmonary lesions. Based on its mechanism of action, we propose an association between the use of etanercept, a tumor necrosis factor alpha (TNF-alpha) inhibitor, and this case of fatal pulmonary mycobacterial infection. We recommend that physicians exercise cautious clinical judgment when initiating etanercept therapy in persons with underlying lung disease, especially in communities in which mycobacterial organisms are highly prevalent. We also advise physicians to maintain a high level of vigilance for late onset granulomatous infection in persons using etanercept.
18484697 Health-related quality of life: validity, reliability, and responsiveness of SF-36, 15D, E 2008 Aug OBJECTIVE: To compare validity, reliability, and responsiveness of generic and disease specific health-related quality of life (HRQOL) instruments in rheumatoid arthritis (RA). METHODS: Two samples of patients completed the Medical Outcomes Study Short Form-36 Health Survey (SF-36), EuroQol (EQ)-5D, 15D, Rheumatoid Arthritis Quality of Life Scale (RAQoL), Health Assessment Questionnaire (HAQ), and visual analog scales (VAS) for pain, fatigue, and global RA. VALIDITY (convergent, discriminant, and known-groups) was evaluated in a cross-section of 200 patients. Reliability was evaluated by agreement (intraclass correlation coefficient; baseline to 2 weeks) and internal consistency (Cronbach's alpha); and responsiveness by the standardized response mean stratified on improvement, status quo, or deterioration in health status after 6 months in 150 patients followed longitudinally. Followup questionnaires (at 2 weeks and 6 months) included questions about changes in health status since baseline. RESULTS: The cross-sectional sample included 77% women, median age 57 years (range 19-87), disease duration 6 years (0-58), with Disease Activity Score 28-joint count (DAS28) of 3.10 (1.21-6.47). The longitudinal sample included 80% women, median age 60 years (22-82). VALIDITY: all instruments discriminated between low, moderate, and high DAS28. Reliability: RAQoL and HAQ displayed good repeatability (ICC > 0.95) and internal consistency (Cronbach's alpha > 0.90). Responsiveness: SF-36 bodily pain scale and VAS pain were responsive to both improvement and deterioration. CONCLUSION: All instruments were valid measures for HRQOL in RA. The RAQoL and HAQ displayed the best reliability, while the SF-36 bodily pain scale and VAS pain were the most responsive. The choice of instrument should depend on the study objectives.
18311836 Autoimmune disease in individuals and close family members and susceptibility to non-Hodgk 2008 Mar OBJECTIVE: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome have been consistently associated with an increased risk of non-Hodgkin's lymphoma (NHL). This study was initiated to evaluate the risks of NHL associated with a personal or family history of a wide range of autoimmune diseases. METHODS: A population-based case-control study was conducted that included 24,728 NHL patients in Denmark (years 1977-1997) and Sweden (years 1964-1998) and 55,632 controls. Using univariate logistic and hierarchical regression models, we determined odds ratios (ORs) of NHL associated with a personal history of hospital-diagnosed autoimmune conditions. Risks of NHL associated with a family history of the same autoimmune conditions were assessed by similar regression analyses that included 25,941 NHL patients and 58,551 controls. RESULTS: A personal history of systemic autoimmune diseases (RA, SLE, Sjögren's syndrome, systemic sclerosis) was clearly linked with NHL risk, both for individual conditions (hierarchical odds ratios [OR(h)] ranged from 1.6 to 5.4) and as a group (OR(h) 2.64 [95% confidence interval (95% CI) 1.72-4.07]). In contrast, a family history of systemic autoimmune diseases was modestly and nonsignificantly associated with NHL (OR(h) 1.31 [95% CI 0.85-2.03]). An increased risk of NHL was found for a personal history of 5 nonsystemic autoimmune conditions (autoimmune hemolytic anemia, Hashimoto thyroiditis, Crohn's disease, psoriasis, and sarcoidosis) (OR(h) ranged from 1.5 to 2.6) of 27 conditions examined. CONCLUSION: Overall, our results demonstrate a strong relationship of personal history of systemic autoimmune diseases with NHL risk and suggest that shared susceptibility may explain a very small fraction of this increase, at best. Positive associations were found for a personal history of some, though far from all, nonsystemic autoimmune conditions.
18821691 Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid 2008 Oct OBJECTIVE: To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA). METHODS: A total of 1,220 patients were randomized (2:1 ratio) in the phase III, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks. RESULTS: At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P<0.0001). Secondary end points including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28 joints (DAS28), DAS28 remission responses (DAS28<2.6), European League Against Rheumatism responses, and systemic markers such as the C-reactive protein and hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs alone. Seventy-three percent of patients in the tocilizumab group had >or=1 adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to >3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients receiving tocilizumab and none of the patients in the control group, and no grade 4 neutropenia was reported. CONCLUSION: Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents.
18538752 Activated T cells complicate the identification of regulatory T cells in rheumatoid arthri 2008 Feb Most cell surface markers for CD4(+)CD25(+) regulatory T cells (Tregs) are also expressed by activated non-regulatory T cells. Recently, CD127 down-regulation was found to identify functional Tregs in healthy individuals, but there are no data from patients with inflammatory conditions. We examined peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis patients with active inflammation and from healthy controls, and found that CD4(+) T cells contained an equal proportion of CD25(+)CD127(-)/low cells in both groups. In patients, not all these cells expressed intracellular FOXP3. Upon activation by anti-CD3/anti-CD28, PBMC rapidly down-regulated CD127, while FOXP3 up-regulation was transitory and occurred in fewer cells. The activated cells were not anergic to restimulation and had no suppressive effects. The distinct kinetics indicate that the FOXP3(-)CD127(-)/low cells in rheumatoid arthritis patients most likely represent activated non-regulatory T cells. This complicates the use of CD127 for identification of Tregs in inflammatory diseases.
16874796 Antirheumatic drug use and the risk of acute myocardial infarction. 2006 Aug 15 OBJECTIVE: To assess the risk of acute myocardial infarction (AMI) associated with the use of disease-modifying antirheumatic drugs (DMARDs) and other medications commonly used in rheumatoid arthritis (RA). METHODS: We conducted a nested case-control analysis within a cohort of subjects with RA, observed between 1999 and 2003, identified from the PharMetrics claims database. For each first AMI hospitalization identified during followup, 10 controls matched on sex, age, and time of study entry were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of AMI associated with the current use of anti-RA therapy, as measured from dispensed prescriptions, after adjustment for AMI risk factors. RESULTS: The cohort included 107,908 subjects (average age 54 years at cohort entry). During followup, 558 AMI cases occurred (3.4 per 1,000 per year). AMI rate was significantly decreased with the current use of any DMARD (adjusted RR 0.80, 95% confidence interval [95% CI] 0.65-0.98). This effect was consistent across all DMARDs, including methotrexate (RR 0.81, 95% CI 0.60-1.08), leflunomide (RR 0.28, 95% CI 0.12-0.65), and other traditional DMARDs (RR 0.67, 95% CI 0.46-0.97), but not biologic agents (RR 1.30, 95% CI 0.92-1.83). AMI rate increased with the use of glucocorticoids (RR 1.32, 95% CI 1.02-1.72) but not with nonselective nonsteroidal antiinflammatory drugs (RR 1.05, 95% CI 0.81-1.36) or cyclooxygenase 2 (COX-2) inhibitors (RR 1.11, 95% CI 0.87-1.43). CONCLUSION: DMARD use is associated with a reduction in AMI risk in patients with RA. No risk increase was found with the COX-2 inhibitors in this population.
17309571 National survey of hemapheresis practice in Hungary 2001-2004. 2007 Feb In the current study, the authors evaluated data provided by Hungarian hemapheresis centers to the National Health Insurance (NHI) organization between 2001 and 2004 with the intention of having costs reimbursed. The primary objective of the present study was to rank data by frequency of indications of therapeutic plasma exchange (TPE). Furthermore, we compared frequency data with the Canadian TPE Registry and reviewed medical evidence regarding the adequacy of applying TPE at chosen indications based on data in literature. It was concluded that the number of TPEs (and thus the reimbursed costs) increased steadily year by year. It is worth considering the difference between the five most frequent indications of TPE in Hungary or in Canada. Clinicians tend to apply TPE in many cases as a last resort treatment of many diseases unresponsive to conventional therapy. Consequently, there are many illnesses for which the value of TPE is still questionable (or unproven) and its use is considered investigational or experimental. Nevertheless, cumulative medical experience does not always confirm the adequacy of TPE in all treatments, retrospectively. Thus, limited financial resources oblige clinicians to be judicious in providing apheresis services.