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19228421 Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis 2009 INTRODUCTION: Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. METHODS: Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. RESULTS: The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P < or = 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (> or = 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 +/- 4.6 versus 13.6 +/- 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P < or = 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02). CONCLUSIONS: Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.
19821383 Assistive technology for rheumatoid arthritis. 2009 Oct 7 BACKGROUND: Provision of assistive technology is a widely used intervention for people with rheumatoid arthritis. Assistive technology is any item used to increase or maintain functional ability in individuals with disabilities. It includes a wide range of products, from low-technology devices to technologically complex equipment. Yet, there are few systematic reviews on the effectiveness of assistive technology in this population. OBJECTIVES: To assess the benefits of assistive technology for adults with rheumatoid arthritis in terms of improving functional ability and reducing pain, and to assess potential adverse effects in terms of psychological discomfort, personal injury or material damage related to device use. SEARCH STRATEGY: We searched the following databases: CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, AMED, ISI Web of Science, PEDro, and OTseeker (to October 2008). In addition, we scanned reference lists, sought grey literature, and had personally communicated with authors. We updated the literature searches in January 2009. SELECTION CRITERIA: Included study designs were randomised controlled trials, clinical controlled trials, controlled before and after studies, and interrupted time series where the effectiveness of assistive technology was evaluated. In addition, comparative observational studies were included if addressing adverse effects. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed study quality. Investigators were contacted to obtain missing information. MAIN RESULTS: Only one randomised controlled trial with 29 participants was included. The study compared the use of an eye drop device to a standard bottle in people with rheumatoid arthritis suffering from persistent dry eyes. The study was considered to have low quality of evidence. The proportions with observed difficulties when using the device to squeeze out drops and getting the drops in the eyes were 10% and 14%, respectively. This compared to 52% and 52% when using the standard bottle (P = 0.001; P = 0.003, respectively). The proportions of participants reporting difficulties with squeezing the bottle, controlling the number of drops, and aiming the drops when using the device were 40%, 44%, and 46% respectively, while using the standard bottle the proportions with difficulties were 72%, 84%, and 76% (P = 0.001; P = 0.003; P = 0.031, respectively). AUTHORS' CONCLUSIONS: Only one trial met the inclusion criteria for this review. Thus, there is very limited evidence for the effect of assistive technology for adults with rheumatoid arthritis and, therefore, an urgent need for high-quality research addressing the effectiveness of commonly used interventions.
20039405 Direct comparison of treatment responses, remission rates, and drug adherence in patients 2010 Jan OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS: The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS: Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.
19332633 A functional haplotype of PADI4 gene in rheumatoid arthritis: positive correlation in a Fr 2009 May OBJECTIVE: A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies. METHODS: DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using an ELISA technique. RESULTS: We focused on PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PADI4_89*G PADI4_90*T), described, respectively, as "nonsusceptible" and "susceptible." A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13%; p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes. CONCLUSION: Our findings confirm those of Japanese, Korean, and Canadian studies and suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations.
19447929 High serum cartilage oligomeric matrix protein determines the subset of patients with earl 2009 Jun OBJECTIVE: To identify the significance of serum cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in patients with early-stage rheumatoid arthritis (RA) in relation to other serologic variables and magnetic resonance imaging (MRI) features. METHODS: Ninety-eight patients with early-stage RA, whose disease duration from onset was less than 2 years, were enrolled. The objective measures at baseline were Disease Activity Score (DAS28), serum C-reactive protein (CRP), serum matrix metalloproteinase-3 (MMP-3), serum antibodies against cyclic citrullinated peptide (anti-CCP), and MRI features of both wrist and finger joints. The MRI features included the number of sites scored positive for synovitis, bone edema, and bone erosion. RESULTS: Serum COMP concentration was not different among groups identified with low, moderate, and high DAS28-CRP values. However, COMP values were statistically high in subjects positive for bone erosions on MRI compared with the subjects who were negative for bone erosions. A positive correlation of COMP with CRP and with MMP-3 values was also identified. CONCLUSION: Elevation of COMP may reflect joint damage that is dependent on the synovial inflammatory process in early-stage RA.
20427829 Evaluation of soft-tissue balance during total knee arthroplasty. 2010 Apr PURPOSE: To evaluate soft-tissue balance during versus after total knee arthroplasty (TKA). METHODS: 18 men and 75 women aged 52 to 85 (mean, 68) years who had moderate-to-severe varus deformity underwent TKAs using the Scorpio non-restrictive geometry posterior-stabilised system (Stryker Howmedica Osteonics; Allendale, [NJ], USA). All surgeries were performed by a single surgeon using the medial parapatellar approach. After the bony and soft-tissue procedures, soft-tissue balance was measured intra-operatively using a tensor/balancer device. The coronal laxity--angles between the cut surfaces of the femur and tibia--were measured at 0 degree (in extension) and 90 degrees (in flexion). The central gap was also measured. Immediate postoperative soft-tissue balance was measured using an arthrometer, while anteroposterior stress radiographs were being taken. A valgus or varus force was applied just above the knee on the lateral or medial side, with the knee counter-supported and at 15 degrees flexion. RESULTS: Intra-operatively, the mean coronal laxity at 0 degree (in extension) and 90 degrees (in flexion) was 2.1 degrees and -1.6 degrees, and the mean central gaps were 21.2 and 23.5 mm, respectively. Immediate postoperative mean coronal laxity was 2.9 degrees, indicating that lateral laxity was greater than medial laxity. The postoperative coronal laxity was positively corrected to the intra-operative coronal laxity at 0 degree (r=0.304, p=0.003), but not to the intra-operative coronal laxity at 90 degrees (r= -0.07, p=0.47). CONCLUSION: Slightly greater lateral laxity was observed after TKA, although equal medial-lateral balance was achieved intra-operatively.
19479704 Impact of Medicare Part D on access to and cost sharing for specialty biologic medications 2009 Jun 15 OBJECTIVE: Many worry that the use of specialty tiering for biologic disease-modifying antirheumatic drugs (DMARDs) by Medicare Part D plans imposes a heavy financial burden on beneficiaries with rheumatoid arthritis (RA). To date, no one has examined the cost-sharing structures for biologic DMARDs in Part D plans or the resulting cost burden for patients. METHODS: We followed 14,929 vulnerable, low-income patients with RA who were enrolled in the Medicare Replacement Drug Demonstration (MRDD) in 2005. As the MRDD population transitioned into Part D in 2006, we examined correlates of Part D enrollment and compared the cost-sharing provisions for biologic DMARDs in the Medicare Advantage and stand-alone plans. We simulated the out-of-pocket costs of beneficiaries under 3 cost-sharing scenarios. RESULTS: Eighty-one percent of MRDD beneficiaries with RA enrolled in Part D. Enrollment predictors were female sex (odds ratio [OR] 1.48, 95% confidence interval [95% CI] 1.32-1.67), prior MRDD benefit use (OR 2.29, 95% CI 2.04-2.58), other self-reported drug coverage (OR 1.53, 95% CI 1.36-1.71), and receiving an MRDD subsidy (OR 2.00, 95% CI 1.74-2.30). Compared with stand-alone plans, Medicare Advantage plans had lower deductibles, lower premiums, and fewer prior authorization, step therapy, and quantity limit restrictions. However, approximately 75% of all plans used coinsurance as the preferred form of cost sharing. Out-of-pocket costs exceeded $4,000 annually in all cost-sharing scenarios. CONCLUSION: Most MRDD beneficiaries with RA enrolled in Part D. Although plans assume some costs for biologic DMARDs, the majority of costs are shifted to beneficiaries and to Medicare. Such cost shifting may place these medications out of the beneficiary's financial reach and expose Medicare to high financial liability.
19409915 New insight into the non-neuronal cholinergic system via studies on chronically painful te 2009 Jun 19 For certain parts of the body, it is nowadays accepted that there is a cholinergic system that is not related to cholinergic innervation, i.e. a non-neuronal cholinergic system. It might be argued that this system is of minor importance. New information obtained shows, however, that the non-neuronal cholinergic system is more widely distributed in the body than what is previously recognised. In recent studies, the existence of such a system has thus been shown for human tendons, especially in chronically painful situations (tendinopathy/tendinosis), in the synovial tissue of patients with rheumatoid arthritis and osteoarthritis, and in the mucosa of ulcerative colitis patients. There is evidence of both acetylcholine (ACh) production and a marked existence of muscarinic (M2) ACh receptors in these situations. The non-neuronal cholinergic system may be involved in the establishment of a 'cholinergic anti-inflammatory pathway' and in proliferative and tissue reorganisation processes via autocrine/paracrine effects. The new information obtained suggests that this system plays an important functional role in chronically painful tendons and in inflammatory conditions. The findings of such a system in various parts of the body, when taken together, show that not only should the classical neuronal cholinergic system be considered in discussion of the cholinergic influences in the body. Additionally, the production of ACh in local cells in the tissues represents an important extra supply of the transmitter. ACh effects can be obtained whether or not there is a cholinergic innervation in the tissue.
20454961 Simplified approach to MR image quantification of the rheumatoid wrist: a pilot study. 2011 Jan OBJECTIVES: To determine an optimal threshold in a simplified 3D-based volumetry of abnormal signals in rheumatoid wrists utilizing contrast and non-contrast MR data, and investigate the feasibility and reliability of this method. MATERIALS AND METHODS: MR images of bilateral hands of 15 active rheumatoid patients were assessed before and 5 months after the initiation of tocilizumab infusion protocol. The volumes of abnormal signals were measured on STIR and post-contrast fat-suppressed T1-weighted images. Three-dimensional volume rendering of the images was used for segmentation of the wrist by an MR technologist and a radiologist. Volumetric data were obtained with variable thresholding (1, 1.25, 1.5, 1.75, and 2 times the muscle signal), and were compared to clinical data and semiquantitative MR scoring (RAMRIS) of the wrist. Intra- and interobserver variability and time needed for volumetry measurements were assessed. RESULTS: The volumetric data correlated favorably with clinical parameters almost throughout the pre-determined thresholds. Interval differences in volumetric data correlated favorably with those of RAMRIS when the threshold was set at more than 1.5 times the muscle signal. The repeatability index was lower than the average of the interval differences in volumetric data when the threshold was set at 1.5-1.75 for STIR data. Intra- and interobserver variability for volumetry was 0.79-0.84. The time required for volumetry was shorter than that for RAMRIS. CONCLUSIONS: These results suggest that a simplified MR volumetric data acquisition may provide gross estimates of disease activity when the threshold is set properly. Such estimation can be achieved quickly by non-imaging specialists and without contrast administration.
21875021 [Optimizing rheumatoid arthritis treatment with rituximab--individualized patient approach 2010 Disease activity assessment is a cornerstone of monitoring rheumatoid arthritis (RA) development and guidance for rituximab treatment. Beside clinical signs and symptoms biomarkers (RF and anti-CCP) are important early predictors of response to therapy and they can predict disease development. Autoantibody (RF and anti-CCP) seropositivity has been associated with positive response to rituximab (RTX) in antiTNF-IR patients, DMARD-IR patients and MTX-naive patients. Selecting therapy for TNF-IR patients providing most likely response it should be taken in consideration results form recently published assessments demonstrating for RTX treated patients significant improvement in DAS28 from baseline versus alternative TNF inhibitor treatment. Recently published NICE treatment guideline is recommending upon antiTNF failure RTX treatment (in combination with MTX) instead antiTNF cycling.
19449016 [How effective is rituximab in rheumatoid arthritis?: lessons learned from clinical practi 2010 Jun OBJECTIVES: Does experience with rituximab treatment of rheumatoid arthritis (RA) in daily clinical practice confirm the results of controlled randomized studies? METHODS: This is a retrospective data-analysis of the first 50 patients from one center with rituximab treatment for RA. The patients received at least one cycle of 2 rituximab infusions (1000 mg, respectively) within 2 weeks. Clinical assessment was performed 3-5 months after the first infusion. RESULTS: The patients were older (mean age, 59 years) as compared to previously published controlled studies. The DAS28 was lower (5.5). The mean prednisolone dose was high (13.4 mg/d). The rheumatoid factor was positive in 88% of patients. Only six patients would have fulfilled inclusion criteria for controlled studies such as prednisolone dose
21138661 [Ventricular diastolic dysfunction in rheumatoid arthritis]. 2009 Rheumatoid arthritis ( RA) is a chronic and systemic articular inflammatory disease, often associated with cardiac manifestations. However, cardiac involvement in RA is not always symptomatic. Previous studies reported high mortality rates for RA and that it was dependent on concurrent heart dis-ease. Myocardial infarction and inflammation have been reported in about 2% of the patients in autopsy studies. The earliest deterioration in cardiac disease is in diastolic function. OBJECTIVE: the aim of this study is to evaluate the ventricular diastolic dysfunction in patients with RA and its relation with the duration of the disease. PATIENTS AND METHODS: Thirty-two RA patients who attended the rheumatology unit at Hospital Cordoba during 2004 participated in this study. A control group was formed by thirty two healthy adults of matched sex and age. RA was diagnosed according to 1987 ACR criteria. None of them had diabetes mellitus, systemic hypertension, chronic lung disease, congenital cardiac malformation, coronary artery disease, arrhytmia or valvular heart disease. Two-dimensional, M-mode, pulsed and color Doppler echocardiography were performed on all these subjects by the same examiner. Diastolic dysfunction was defined when the E/A ratio was <1 (E wave velocity decreased, A wave velocity increased) , and desaceleration time (DT) and isovolumic relaxation time (IRT) were prolonged. Ap-value < 0.05 was considered as significant. RESULTS: The mean ages were 48,38 11,08 for patients and 46,81 9,96 for the control group.There were no significant differences between age, sex, heart rate, and systolic and diastolic blood pressure between RA patients and controls. Higher proportion of RA patients had E/A ratio < 1compared with the controls ( p<00001). The mean IRT value was significantly longer than in controls ( 83,59 1 13,82 vs 74,41 i 15,14 p<0.01). There was no correlation between the duration of illness and E/A ratio and IRT ( p=0.70, p=0.13). CONCLUSION: Diastolic function was impaired in patients with RA. There was no relation between some of the parameters of ventricular diastolic function and disease duration. These findings suggest a subclinical myocardial involvement in RA patients.
21132352 Actively targeted low-dose camptothecin as a safe, long-acting, disease-modifying nanomedi 2011 Apr PURPOSE: Camptothecin (CPT), a potent topoisomerase I inhibitor, was originally discovered as an anticancer agent to induce programmed cell death of cancer cells. Recent evidence suggests that, similar to cancer, alterations in apoptosis and over-proliferation of key effector cells in the arthritic joint result in rheumatoid arthritis (RA) pathogenesis. Initial in vitro studies have suggested that camptothecin inhibits synoviocyte proliferation, matrix metalloproteinases expression in chrondrocytes and angiogenesis. This study is one of the first to test, in vivo, RA as a new indication for CPT. METHODS: To circumvent insolubility, instability and toxicity of CPT, we used biocompatible, biodegradable and targeted sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). We also surface-modified CPT-SSM with vasoactive intestinal peptide (VIP) for active targeting. We then determined whether this nanomedicine abrogated collagen-induced arthritis (CIA) in mice. RESULTS: Based on our findings, this is the first study to report that CPT was found to be efficacious against CIA at concentrations significantly lower than usual anti-cancer dose. Furthermore, a single subcutaneous injection of CPT-SSM-VIP (0.1 mg/kg) administered to CIA mice mitigated joint inflammation for at least 32 days thereafter without systemic toxicity. CPT alone needed at least 10-fold higher dose to achieve the same effect, albeit with some vacuolization in liver histology. CONCLUSION: We propose that CPT-SSM-VIP is a promising targeted nanomedicine and should be further developed as a safe, long-acting, disease-modifying pharmaceutical product for RA.
19246078 The effect of infliximab and timing of vaccination on the humoral response to influenza va 2010 Jun OBJECTIVES: To assess the effect of the timing of vaccination in relation to administration of infliximab on the efficacy and safety of influenza vaccine in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: The study population comprised 38 patients treated with infliximab at a mean dosage of 3 mg/kg (20 RA patients; 18 AS patients; 23 RA controls (treated with disease modifying antirheumatic drugs other than anti-tumor necrosis factor-alpha; and 17 healthy controls). Split-virion inactivated vaccine containing 15 mug hemagglutinin/dose of each of A/New Caledionan/20/1999 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 (M) was used. Patients treated with infliximab were divided into 2 groups: 22 were vaccinated on the day of administration of infliximab, while 16 received the vaccine 3 weeks after infliximab. Baseline and 4- to 6-week clinical assessment of disease activity included erythrocyte sedimentation rate and C-reactive protein for all patients, the 28-joint disease-activity score for RA patients, and Bath Ankylosing Spondylitis Disease Activity Index for AS patients. Hemagglutination inhibition (HI) antibodies were tested by a standard World Health Organization procedure. Response was defined as >or=4-fold rise in HI antibodies 4 to 6 weeks after vaccination, or seroconversion in patients with a nonprotective baseline level of antibodies (<1/40). Geometric mean titers (GMT) were calculated to assess the immunity of the whole group. RESULTS: At baseline, RA patients and controls had similar occurrence of protective levels of HI antibodies and GMT, while AS patients had lower levels reflecting lower rates of previous vaccination. Four weeks after vaccination, a significant and similar increase in GMT for each antigen was observed in all groups (P < 0.004) except in the RA-infliximab group, vaccinated 3 weeks after administration of infliximab, in whom the increase in GMT was not significant for H1N1 (P = 0.12) and H3 (P = 0.06). AS patients demonstrated an increase in GMT, independently of the time of vaccination. The percentage of responders was similar in all groups. The response was not affected by variables such as age, gender, methotrexate, or prednisone use. Parameters of disease activity remained unchanged. No adverse effects other than injection site pain were recorded. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in RA and AS patients treated with infliximab.
20231201 Risk factor profiles for atherosclerotic cardiovascular disease in black and other African 2010 May OBJECTIVE: Black Africans reportedly experience a distinctly low risk for atherosclerotic cardiovascular disease (CVD). We investigated whether this protection was present among Africans with established rheumatoid arthritis (RA). METHODS: We determined disparities in CVD risk factor profiles (major conventional: hypertension, dyslipidemia, smoking, and diabetes; other conventional: underweight, obesity, metabolic syndrome, chronic kidney disease, alcohol consumption, tension, depression, and body height; nonconventional: rheumatoid factor status and markers of inflammation) and arterial stiffness (brachial pulse pressure) between 291 black and 335 other (229 white, 64 Asian, and 42 mixed ancestry) consecutive Africans with RA in multivariable regression models. RESULTS: After adjusting for demographic characteristics and healthcare sector attendance, black Africans had more prevalent hypertension (OR 1.76, p = 0.01) and diabetes (OR 1.90, p = 0.07), smoked less frequently (OR 0.12, p < 0.0001), and had concurrent lower total and high-density lipoprotein cholesterol concentrations that resulted in unaltered atherogenic indices (p = 0.2) than the other participants in the study. These findings translated into global scores for major conventional risk factor-mediated future CVD event rates that were not reduced in black patients. Proportions of individual metabolic syndrome components differed between black and other patients but their total numbers of metabolic risk factors (p = 0.4) and metabolic syndrome frequencies (OR 1.44, p = 0.1) were similar. Black ethnicity did not independently associate with rheumatoid factor status, markers of inflammation, and brachial pulse pressures. CONCLUSION: The overall conventional and nonconventional atherosclerotic CVD risk burdens and arterial stiffness were not reduced in black patients with RA. CVD risk should be assessed and managed independent of ethnic origin and epidemiological transition stage in RA.
18336871 Role of interleukin-6 in the anemia of chronic disease. 2009 Apr OBJECTIVES: To review evidence supporting the involvement of interleukin-6 in the pathophysiology of anemia of chronic disease, to discuss the possible molecular mechanisms driving this condition in patients with end-stage renal disease and rheumatoid arthritis, and to review clinical manifestations in these patients. METHODS: A literature search was performed using MEDLINE and the reference lists of relevant review articles. The following key words were used in the MEDLINE search: interleukin-6, "anemia of chronic disease" OR "anemia of inflammation," "pathophysiology," "end-stage renal disease," and "rheumatoid arthritis." The search was limited to English-language articles. RESULTS: Interleukin-6 is a multifunctional cytokine that regulates the hepatic acute-phase response, the immune response, inflammation, and hematopoiesis. Interleukin-6 appears to be the central mediator of anemia of chronic disease in a range of inflammatory diseases, including end-stage renal disease and rheumatoid arthritis, through increased generation of hepcidin and the resultant alterations in iron metabolism. Clinically, patients with anemia of chronic disease are more likely to experience increased disease severity and duration than patients who have chronic disease without anemia. CONCLUSIONS: The integral role of interleukin-6 in the pathogenesis of anemia of chronic disease suggests that it could be an important therapeutic target. Currently available treatments target interleukin-1, and tumor necrosis factor-alpha and its receptors, and have been only partially successful. Given the complexity of the cytokine pathways that are involved in the pathogenesis of inflammatory disease, further studies are required to test other molecular targets.
20423835 [Therapeutic effect of infliximab on moderate and severe active rheumatoid arthritis]. 2010 Apr OBJECTIVE: To evaluate the clinical efficacy of infliximab in the treatment of moderate and severe active rheumatoid arthritis (RA). METHODS: This randomized double-blind II/III clinical trial involved 30 patients with moderate and severe active RA, who were randomly allocated into 3 groups (groups A, B, and C) at the ratio of 3:1:1. At weeks 0, 2, 6, and 14, the patients in groups A and C received infliximab or placebo, and those in group B had placebo at week 14 with a stable background dose of methotrexate. The indicators for efficacy evaluation included the proportions of ACR20/50/70 of the responders and DAS28. The sharp scores of the hand joints were recorded before and after the treatment. RESULTS: Twenty-nine patients completed the clinical trial (18 in group A, 5 in group B, and 6 in group C). At week 14, the proportions of ACR20/50/70 in the 3 groups reached 83.33%, 60%, and 33.33%, respectively (P<0.05), as compared to 100%, 100%, and 33.33% at week 18 (P<0.05). The other indicators for clinical efficacy evaluation also suggested similar clinical improvement of the patients (P=0.000). The proportions of the patients with DAS28<3.2 and DAS28<2.6 were significantly different. Compared to the baseline, the Sharp scores in group A showed no significant changes at week 18 (P>0.930), while those in group C exhibited significant radiographic progression (P<0.044). CONCLUSION: Infliximab produces good short-term therapeutic effect against moderate and severe active RA and may help arrest the radiographic progression of the diseases, which can be more obvious in patients with moderate severity.
19950308 "Should I tell my employer and coworkers I have arthritis?" A longitudinal examination of 2009 Dec 15 OBJECTIVE: To examine arthritis self-disclosure at work, factors associated with disclosure, and prospective relationships of self-disclosure and work place support with changes to work place interactions, work transitions, and work place stress. METHODS: Using a structured questionnaire, participants with osteoarthritis or inflammatory arthritis were interviewed at 4 time points, 18 months apart. At time 1, all participants (n = 490; 381 women, 109 men) were employed. Of the entire sample, 71% were retained throughout the study. Respondents were recruited using community advertising and from rheumatology and rehabilitation clinics. Self-disclosure and perceived support from managers and coworkers was assessed, as well as demographic, illness, work-context, and psychological variables. Generalized estimating equations modeled associations of disclosure and support on changes at work (e.g., job disruptions, work place stress). RESULTS: At each time point, 70.6-76.6% of participants had self-disclosed arthritis to their manager and 85.2-88.1% had told a coworker. Intraindividual variability in disclosure was considerable. Factors associated with self-disclosure were often inconsistent over time, with the exception of variables assessing the need to self-disclose (e.g., activity limitations) and perceived coworker support. Self-disclosure was not associated with changes to work. However, coworker support was related to fewer job disruptions, help with work tasks, and being less likely to reduce hours. Perceived managerial support was associated with less work place stress. CONCLUSION: Greater awareness is needed about issues related to self-disclosing arthritis at work. This study emphasizes the importance of a supportive work place, especially supportive coworkers, in decisions to discuss arthritis at work and in changes to work that might enable people to remain employed.
19321514 6q23 polymorphisms in rheumatoid arthritis Spanish patients. 2009 Jun OBJECTIVE: The aim of this work is to replicate the role of two recently described RA genetic markers (rs10499194 and rs6920220) situated at 6q23 in the autoantibody-positive phenotype. METHODS: A case-control study (630 RA patients and 664 healthy blood donors, all white Spaniards) was performed with two single nucleotide polymorphisms (rs6920220 and rs10499194) situated at 6q23. Genotyping was performed by TaqMan technology; autoantibody-stratified analyses in RA patients were also undertaken to replicate the previously reported effect of these polymorphisms. RESULTS: No association was observed for rs10499194 even after autoantibody stratification. The minor allele frequency of rs6920220 was higher in anti-CCP or RF-positive patients than in controls (P = 0.014 and P = 0.015 respectively), thus replicating previous findings. CONCLUSIONS: Our data replicate the association of rs6920220 with autoantibody-positive RA disease, although not for rs10499194.
20593016 The gene expression profile in the synovium as a predictor of the clinical response to inf 2010 Jun 25 BACKGROUND: Although the use of TNF inhibitors has fundamentally changed the way rheumatoid arthritis (RA) is treated, not all patients respond well. It is desirable to facilitate the identification of responding and non-responding patients prior to treatment, not only to avoid unnecessary treatment but also for financial reasons. In this work we have investigated the transcriptional profile of synovial tissue sampled from RA patients before anti-TNF treatment with the aim to identify biomarkers predictive of response. METHODOLOGY/PRINCIPAL FINDINGS: Synovial tissue samples were obtained by arthroscopy from 62 RA patients before the initiation of infliximab treatment. RNA was extracted and gene expression profiling was performed using an in-house spotted long oligonucleotide array covering 17972 unique genes. Tissue sections were also analyzed by immunohistochemistry to evaluate cell infiltrates. Response to infliximab treatment was assessed according to the EULAR response criteria. The presence of lymphocyte aggregates dominated the expression profiles and a significant overrepresentation of lymphocyte aggregates in good responding patients confounded the analyses. A statistical model was set up to control for the effect of aggregates, but no differences could be identified between responders and non-responders. Subsequently, the patients were split into lymphocyte aggregate positive- and negative patients. No statistically significant differences could be identified except for 38 transcripts associated with differences between good- and non-responders in aggregate positive patients. A profile was identified in these genes that indicated a higher level of metabolism in good responding patients, which indirectly can be connected to increased inflammation. CONCLUSIONS/SIGNIFICANCE: It is pivotal to account for the presence of lymphoid aggregates when studying gene expression patterns in rheumatoid synovial tissue. In spite of our original hypothesis, the data do not support the notion that microarray analysis of whole synovial biopsy specimens can be used in the context of personalized medicine to identify non-responders to anti-TNF therapy before the initiation of treatment.