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ID PMID Title PublicationDate abstract
21452265 Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthrit 2011 Apr OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Disease-modifying therapies that improve risk factors for CVD, such as dyslipidemia, are desired. This study used an electronic health record to determine if hydroxychloroquine (HCQ) use was associated with an improvement in lipid levels in an inception RA cohort. METHODS: All adult individuals with the initial diagnosis of RA between January 1, 2001, and March 31, 2008, were identified (n=1,539). Only patients with at least one lipid level post-RA diagnosis were included (n=706). Information on demographics, medical history, body mass index (BMI), laboratory measures, and medications were collected at office visits. Potential risk and protective factors for dyslipidemia were controlled for in linear mixed-effects regression models for low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglycerides, LDL/HDL, and total cholesterol/HDL. RESULTS: Patients were 69% women and 98% white, with a median age of 65 years and a median BMI of 29.8 kg/m2. In the adjusted regression models, HCQ use was associated with the following average differences in lipids: LDL decrease of 7.55 mg/dl (P<0.001), HDL increase of 1.02 mg/dl (P=0.20), total cholesterol decrease of 7.70 mg/dl (P=0.002), triglycerides decrease of 10.91 mg/dl (P=0.06), LDL/HDL decrease of 0.136 (P=0.008), and total cholesterol/HDL decrease of 0.191 (P=0.006), which were stable over time. CONCLUSION: Use of HCQ in this RA cohort was independently associated with a significant decrease in LDL, total cholesterol, LDL/HDL, and total cholesterol/HDL. Considering these results, its safety profile, and low cost, HCQ remains a valuable initial or adjunct therapy in this patient population at high risk for CVD.
22859345 Palindromic rheumatism with positive anticitrullinated peptide/protein antibodies is not s 2012 Oct OBJECTIVE: To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR). METHODS: We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods. RESULTS: Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45-0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77-7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA. CONCLUSION: ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.
21347804 The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active r 2011 Aug We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.
21827750 Regulatory T-cells in systemic lupus erythematosus and rheumatoid arthritis. 2011 Dec 1 Regulatory T-cells (Tregs) are the guardians of peripheral tolerance acting to prevent autoimmune diseases such as systemic lupus erythomatosus (SLE) and rheumatoid arthritis (RA). Defects in Tregs have been reported in these two diseases despite significant differences in their clinical phenotype and pathogenesis. In both diseases the potency of Treg fails to keep pace with the activation of effector cells and are unable to resist the ensuing inflammation. This review will discuss the phenotypic, numeric, and functional abnormalities in Tregs and their role in patients and murine models of SLE and RA.
21851009 [Determination of antibodies against cyclic citrullinated peptide in rheumatoid arthritis] 2011 Jun The ability of the synthetic peptide IMG-5, that reproduces one of the antigenic determinants of the protein filaggrin, to show antigenic activity was studied when anti-cyclic citrullinated peptide antibodies (ACCPAb) to filaggrin were found in the serum samples of patients with rheumatoid arthritis (RA). The binding of IMG-5 to ACCPAb has been shown to be specific (dose-dependent and reversible). The serum samples from patients with RA, controls, and donors show a significant difference in the interaction of the synthetic peptide with ACCPAb (p < 0.005 and p < 0.0001, respectively). The level of IgM rheumatoid factor (RF) detected in patients with RA differs greatly from that in the controls. In the patients with RA versus the controls, the specificity of ACCPAb determination was as high as 87; and the sensitivity was 40.5%. When ACCPAbs were determined using the commercial kit CCP, the specificity and sensitivity were 94 and 47.3%, respectively. The specificity of RF detection was equal to 50% and the sensitivity was 70%. The sensitivity of the test using IMG-5 is a maximum in X-ray stage IRA (69.2%) and falls in its stage III (26.7%). On the contrary, the sensitivity of the commercial kit and RF determination increases from X-ray stage I (46.2 and 53.8%, respectively) to II (66.7 and 80%). The sensitivity of the used tests in varying RA activities has demonstrated that they are most effective in patients with moderate RA activity. The concurrent detection of ACCPAb and RF increases the probability of differentiating RA from other rheumatic diseases.
21303509 Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with 2011 Feb 8 INTRODUCTION: Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA). METHODS: Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis. RESULTS: Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement. CONCLUSIONS: Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients.
21574707 Naturalistically observed swearing, emotional support, and depressive symptoms in women co 2011 Nov OBJECTIVE: The goal of this study was to explore the intra- and interpersonal consequences of swearing. Specifically, it investigated what implications swearing has for coping with and adjustment to illness. METHODS: The present project combined data from two pilot studies of 13 women with rheumatoid arthritis and 21 women with breast cancer. Participants wore the Electronically Activated Recorder, an unobtrusive observation sampling method that periodically records snippets of ambient sounds, on weekends to track spontaneous swearing in their daily interactions, and completed self-reported measures of depressive symptoms and emotional support. RESULTS: Naturalistically observed swearing in the presence of others, but not alone, was related to decreases in reported emotional support and increases in depressive symptoms over the study period. Further, decreases in emotional support mediated the effect of swearing on disease-severity adjusted changes in depressive symptoms. CONCLUSION: These exploratory results are consistent with the notion that swearing can sometimes repel emotional support at the expense of psychological adjustment. This is one of the first studies to examine the role of swearing, a ubiquitous but understudied psychological phenomenon, in a medical context.
21955850 New insight in the mechanism of action of rituximab: the interferon signature towards pers 2011 Sep Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder of the musculoskeletal system that may cause permanent joint damage. The disease has a major impact on the quality of life of affected individuals, costs for the health care system, and society. Currently, no curative treatment is available, and patients are subjected to a prolonged course of treatment. Due to their role in the pathogenesis of RA, B cells have become an attractive target for therapy. Rituximab (Mabthera®/Rituxan®) is a therapeutic monoclonal antibody against CD20 expressed on B cells, which is effective in depleting B cells and approved worldwide for the treatment of RA. Rituximab was shown to be highly beneficial in decreasing clinical symptoms, safe, and well tolerated. However, clinical experience revealed that approximately 30-40% of RA patients do not respond to it. Given the destructive nature of RA, the risk of adverse effects, and considerable costs for therapy, there is a strong need to make predictions on the clinical outcome before the start of therapy. Since nearly all treated patients experience an effective depletion of circulating B cells, questions have been raised concerning the mechanism of action. In this review, novel developments, in particular the findings on the role of the interferon system, will be highlighted. This may add new and important information to our understanding of the mechanism that underlies the clinical outcome of rituximab treatment and may lead to the identification of biomarkers to predict the response.
21240057 Systematic review of thiopurine methyltransferase genotype and enzymatic testing strategie 2011 Apr BACKGROUND: An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more accurate testing for diagnosis and treatment. Thiopurine methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs used in pediatric leukemia, rheumatoid arthritis, and inflammatory bowel disease. The objective was to review the literature systematically to ascertain the performance characteristics of current genotype and enzymatic testing technologies for TPMT. METHODS: A systematic review of the literature was conducted to describe TPMT testing technologies. Eligible studies evaluated either a TPMT genotype or TPMT phenotype technology in comparison to a reference standard and expressed results in terms of sensitivity and specificity or positive/negative predictive value. The laboratory technique was recorded, and the quality of the identified studies was assessed using a modified Critical Appraisal Skills Program tool. RESULTS: Seventeen studies were reviewed. The sensitivity and specificity of the genotype test ranged from 55% to 100% and from 94% to 100%, respectively. The sensitivity and specificity of the phenotype test ranged from 92% to 100% and from 86% to 98%, respectively. A variety of laboratory techniques were employed. Reviewed studies were of low methodological quality. CONCLUSIONS: The systematic review of TPMT test strategies found that available technologies demonstrated high values for sensitivity and specificity, however, there was a lack of a single gold standard and most studies were of poor quality. Disregard for study sample size and confounding factors such as concurrent medications and blood transfusions were the main contributors to low quality. There were also inconsistencies in the selection of a reference standard which complicated the interpretation of the findings.
22198690 Baseline HAQ and SF-36 questionnaire scores cannot predict clinical remission, radiographi 2012 Dec This study evaluates prospectively whether baseline scores [Health Assessment Questionnaire (HAQ) and SF-36] can predict clinical and radiographic evolution in a cohort of early rheumatoid arthritis (RA) during a 3-year follow-up. Forty consecutive early RA patients were followed for 3 years, while receiving standardized treatment according to a pre-established protocol. HAQ and SF-36 were administered at the initial evaluation and at 3, 6, 12, 18, 24 and 36 months. Hands and feet radiographs were obtained at the initial evaluation and at 12, 24 and 36 months. Preselected outcomes were the occurrence of radiographic erosions, the achievement of an EULAR remission, low disease activity status and the need for biological therapy. The mean age at onset was 45 years with a 90% female predominance. Erosions were found in 42% of patients at T0 and in 70% after 3 years (P < 0.001). At T0, the proportion of patients in remission, low, moderate or high disease activity was 0, 0, 7.5 and 92.5% and 22.5, 7.5, 32.5 and 37.5%, respectively, at 3 years. The mean baseline HAQ score was 1.89 and 0.77 by the third year (P < 0.0001). Most SF-36 domains showed significant improvement except for general state and vitality. Biological therapy was deemed necessary in 22.5% of patients. The initial HAQ and SF-36 scores were not associated with clinical remission, bone erosions or the need for biological therapy at 36 months. The HAQ and SF-36 scores measured at baseline could not predict at 3 years, the preselected outcomes in a Brazilian cohort.
21641515 Association between tongue appearance in Traditional Chinese Medicine and effective respon 2011 Jun OBJECTIVE: Explore the associations between the tongue appearances in Traditional Chinese Medicine (TCM) and effective response (ACR20 response based on American College of Rheumatology) in rheumatoid arthritis (RA) patients treated with Chinese medicine (CM) and western biomedical combination therapy (WM). METHODS: This study used the data from a previous multi-center randomized-controlled clinical trial. Data pertaining to tongue coating and tongue body color were collected. In order to simplify the tongue diagnosis for easily understood by biomedical professionals, only two typical tongue coating (white and yellow) and four typical tongue body colors (purple, pink, pale and red) were identified for this analysis. 170 cases with clear tongue coating and 198 cases with clear tongue body color in TCM treatment (Glucosidorum Tripterygll Totorum tablets and Yishen Juanbi tablets) group, 181 cases with identified tongue coating and 189 cases with identified tongue body color in WM treatment (diclofenec, methotrexate and sulfasalazine) group were included for the analysis. The ACR20 response at 12 weeks and 24 weeks were used as an outcome measure of efficacy. The effective rates in patients with different tongue appearances were analyzed with Chi-square method and the association between the changes of tongue coating/body color and the ACR20 response was analyzed with a repeated measures logistic regression analysis. RESULTS: At 12 weeks, the ACR20 responses in the patients treated with CM and WM therapy were 33.6% and 53.0%, respectively, and at 24 weeks, they were 57.9% and 84.3%, respectively. RA patients with white tongue coating showed higher effective rate than those patients with yellow tongue coating in the treatment with WM intervention (p<0.05), and there was no difference in the patients with CM intervention. Further association analysis showed that TCM would be less effective for the patients with pale tongue body (p=0.0323), and WM would be less effective for the patients with purple or red tongue body (p=0.0291 and 0.0027, respectively). CONCLUSION: TCM was less effective for the patients with pale tongue body, and WM was be less effective for the patients with purple or red tongue body, or white tongue coating. The results suggest that tongue coating and body color might be used to help identify a subset of RA patients both for CM and WM interventions.
21881984 Pulmonary tuberculosis and tuberculous arthritis of knee joint associated with rheumatoid 2012 Sep Tuberculosis infection (TB) is one of the most important problems for the rheumatoid arthritis (RA) patients treated with anti-TNF agents. Pulmonary tuberculosis is the most common clinic form of the TB in these patients. However, tuberculosis arthritis is very rare. We present here a 72-year-old Caucasian woman with seropositive RA, treated with etanercept/adalimumab for the last 2 years, who presented with resistant knee pain and joint effusion. We believe that this treatment caused the tuberculosis in this patient, which is the most worried complication. Interestingly, tuberculosis was in the knee joint at this time.
23275019 Latent variable indirect response modeling of categorical endpoints representing change fr 2013 Feb Accurate exposure-response modeling is important in drug development. Methods are still evolving in the use of mechanistic, e.g., indirect response (IDR) models to relate discrete endpoints, mostly of the ordered categorical form, to placebo/co-medication effect and drug exposure. When the discrete endpoint is derived using change-from-baseline measurements, a mechanistic exposure-response modeling approach requires adjustment to maintain appropriate interpretation. This manuscript describes a new modeling method that integrates a latent-variable representation of IDR models with standard logistic regression. The new method also extends to general link functions that cover probit regression or continuous clinical endpoint modeling. Compared to an earlier latent variable approach that constrained the baseline probability of response to be 0, placebo effect parameters in the new model formulation are more readily interpretable and can be separately estimated from placebo data, thus allowing convenient and robust model estimation. A general inherent connection of some latent variable representations with baseline-normalized standard IDR models is derived. For describing clinical response endpoints, Type I and Type III IDR models are shown to be equivalent, therefore there are only three identifiable IDR models. This approach was applied to data from two phase III clinical trials of intravenously administered golimumab for the treatment of rheumatoid arthritis, where 20, 50, and 70% improvement in the American College of Rheumatology disease severity criteria were used as efficacy endpoints. Likelihood profiling and visual predictive checks showed reasonable parameter estimation precision and model performance.
23111637 Roles of Wnt signals in bone resorption during physiological and pathological states. 2013 Jan Osteoclasts, multinucleated giant cells, are responsible for bone resorption in physiological and pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclasts develop from the monocyte/macrophage lineage under the strict control of bone-forming osteoblasts. Osteoblast-lineage cells express two cytokines essential for osteoclast differentiation, colony-stimulating factor-1, and receptor activator of nuclear factor κB ligand (RANKL) and also express osteoprotegerin, a soluble decoy receptor for RANKL. The signaling molecule Wnt has been shown to be important for the differentiation of osteoblasts through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Recent studies have established that Wnt-mediated signals are also crucial for bone resorption in both physiological and pathological conditions. In this review, we introduce recent advances in roles of Wnt signaling in bone formation and bone resorption.
23079082 Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rh 2012 Oct 18 INTRODUCTION: Recent studies revealed that co-morbidity and mortality due to cardiovascular disease are increased in patients with rheumatoid arthritis (RA) but little is known about factors involved in these manifestations. This study aimed at characterizing the impact of arthritis on oxidative stress status and tissue fibrosis in the heart of rats with adjuvant-induced arthritis (AIA). METHODS: AIA was induced with complete Freund's adjuvant in female Lewis rats. Animals were treated by oral administration of vehicle or angiotensin-converting enzyme inhibitor ramipril (10 mg/kg/day) for 28 days, beginning 1 day after arthritis induction. Isolated adult cardiomyocytes were exposed to 10 μM 4-hydroxynonenal (HNE) for 24 hours in the presence or absence of 10 μM ramipril. RESULTS: Compared to controls, AIA rats showed significant 55 and 30% increase of 4-HNE/protein adducts in serum and left ventricular (LV) tissues, respectively. Cardiac mitochondrial NADP+-isocitrate dehydrogenase (mNADP-ICDH) activity decreased by 25% in AIA rats without any changes in its protein and mRNA expression. The loss of mNADP-ICDH activity was correlated with enhanced accumulation of HNE/mNADP-ICDH adducts as well as with decrease of glutathione and NADPH. Angiotensin II type 1 receptor (AT1R) expression and tissue fibrosis were induced in LV tissues from AIA rats. In isolated cardiomyocytes, HNE significantly decreased mNADP-ICDH activity and enhanced type I collagen and connective tissue growth factor expression. The oral administration of ramipril significantly reduced HNE and AT1R levels and restored mNADP-ICDH activity and redox status in LV tissues of AIA rats. The protective effects of this drug were also evident from the decrease in arthritis scoring and inflammatory markers. CONCLUSION: Collectively, our findings disclosed that AIA induced oxidative stress and fibrosis in the heart. The fact that ramipril attenuates inflammation, oxidative stress and tissue fibrosis may provide a novel strategy to prevent heart diseases in RA.
21548145 Long term results of matched hemiresection interposition arthroplasty for DRUJ arthritis i 2011 INTRODUCTION: The distal radioulnar joint (DRUJ) is commonly affected in rheumatoid arthritis and is associated with significant functional morbidity. The aim of our study is to review our results with matched hemi-resection interposition arthroplasty in patients with DRUJ arthritis. METHODS: This was a retrospective study of 39 patients with 51 wrists that were treated at Queen Mary Hospital in Hong Kong from 1989 to 2007. All patients underwent matched hemi-resection interposition arthroplasty and dorsal wrist synovectomy. Long arm hinged elbow brace was used for three weeks followed by intensive rehabilitation up to twelve weeks. The indicators of outcome included range of motion assessment, pain, wrist stiffness, grip of strength and need for revision assessed during follow-up. Statistical analysis was performed with student t-test. RESULTS: The average age of patients was 50.5 years (25 to 77 years) and there was a 35:4 female to male ratio. The average follow up was 4.5 years ranging from 1 to 18 years. Associated extensor tendon ruptures were found in 31.4% patients. The average increase in supination was from 73 degrees preoperatively to 81 degrees at long term follow up (p = 0.10 at 1 year and 0.13 at long term follow-up). The average increase in pronation was from 68 degrees preoperatively to 74 degrees on long term follow up (p = 0.57 at 1 year and 0.02 at long term follow-up). There was evidence of painless, relatively stiff but functional wrist in 37.25% of patients. There was an increase in grip strength from an average of 6.1 kilogram force preoperatively to an average of 11.5 kilogram force at follow-up (p = 0.004 at 1 year and 0.15 at long term follow-up). Complete relief of ulnar sided pain was seen in 43 wrists (84%), partial relief was seen in 7 wrists (13.7%) and no relief was found in one wrist (1.9%). CONCLUSIONS: DRUJ arthroplasty is a rewarding procedure and most of the patients obtain pain free movement.
22556105 Incomplete reporting of recruitment information in clinical trials of biologic agents for 2012 Oct OBJECTIVE: It is important to evaluate how a randomized controlled trial (RCT) sample was assembled from the general patient population in order to determine whether a patient differs from those who participated in the trial in a meaningful way. The aim of this study is to assess the adequacy of reporting of the recruitment process of rheumatoid arthritis (RA) patients participating in RCTs with biologic agents. METHODS: We searched PubMed for all reports of RCTs involving etanercept, infliximab, adalimumab, golimumab, certolizumab, abatacept, tocilizumab, and rituximab in RA patients. Data recorded were eligibility fraction, enrollment fraction, recruitment fraction, and number of patients needed to be screened (NNS) in order to randomize 1 participant. RESULTS: Of the 66 trials included in the analysis, 23 (35%) reported the number of individuals assessed by investigators for eligibility, and 18 (27%) reported the number eligible for participation. Of the studies that reported quantitative recruitment information, the median eligibility fraction was 80.6% (interquartile range [IQR] 71.8-91.1%) and the median enrollment fraction was 100% (IQR 88.4-100%). The median NNS was found to be 1.28 (IQR 1.18-1.43). CONCLUSION: A substantial majority of RCTs conducted in RA patients with biologic agents did not provide sufficient information about the patient recruitment process, which makes assessments of external validity difficult. The rate of reporting of the recruitment process in this study was found to be lower as compared to similar studies conducted in different specialties.
23242389 Safety of tumor necrosis factor inhibitors use for rheumatoid arthritis and ankylosing spo 2013 Mar Multiple studies of patients in Western countries with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have indicated increased risk for active tuberculosis (TB) and other infections among these individuals. It has also been consistently reported that patients receiving tumor necrosis factor (TNF) inhibitors for these conditions have higher rates of active TB and other infections than RA or AS patients not receiving these medications. These issues have been studied less extensively in the Asia and Africa-Middle East regions, and information from these regions is important because of higher rates of TB in the general population. This paper reviews studies of RA and AS patients from Asia, Africa, and the Middle East who received TNF inhibitors. A literature search was conducted using http://www.ncbi.nlm.nih.gov/pubmed to collect and report these data. The years included in the PubMed literature search ranged from January 2000 to October 2011. Additionally, information from the China Hospital Knowledge Database was used to report data from Chinese patients with RA and AS treated with TNF inhibitors. Results from these studies indicate that the risk for active TB and other infections in AS and RA patients from Asia, Africa, and the Middle East are increased in patients receiving TNF inhibitors and that the risk is higher among those treated with monoclonal antibodies versus soluble TNF receptor.
22459416 Mortality in rheumatoid arthritis over the last fifty years: systematic review and meta-an 2013 Jan OBJECTIVE: Mortality rates in patients with rheumatoid arthritis (RA) have been reported to be higher than for the general population. Fortunately, efficient therapies have reduced disease activity and may be able to diminish the excess mortality risk. This study was designed to investigate RA mortality over the last 50 years by systematic review of the literature and meta-analysis. METHODS: Data to January 2010 in the Medline, Cochrane and Embase databases were searched with the keywords "rheumatoid arthritis", "epidemiologic methods" and "mortality". Inclusion criteria were (i) longitudinal study, (ii) early RA patients, (iii) number of deaths and mean patient follow-up. Incidence mortality rates (IMR) were calculated and standardized mortality rates (SMR) were extracted when available. A meta-analysis by periods of inclusion and a Poisson regression were used to model IMR. Available SMR were computed as a meta-analysis. RESULTS: A total of 11 longitudinal studies starting from 1955 to 1995, representing 51,819 patients, met the inclusion criteria. Mean IMR was 2.7/100 person-years of follow-up (95% confidence interval [CI]: 2.2, 3.3) and ranged from 1.0 to 5.2/100 person-years. A decreasing IMR was found in the meta-analyses. Poisson regression analysis indicated a decrease in IMR of 2.3% per year (95%CI: 2.1; 2.6). SMR was available in 8 studies: the meta-SMR was 1.47 (95%CI: 1.19; 1.83) and no decrease was seen over time in the meta-regression. CONCLUSION: Mortality has decreased among RA patients over the past decades but remained higher than in the general population as assessed by the IMR and the SMR over time.
20851921 Osteoclast activity and subtypes as a function of physiology and pathology--implications f 2011 Feb Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate that osteoclasts have different subtypes depending on their location, genotype, and possibly in response to drug intervention. The aim of the current review is to describe the subtypes of osteoclasts in four different settings: 1) physiological, in relation to turnover of different bone types; 2) pathological, as exemplified by monogenomic disorders; 3) pathological, as identified by different disorders; and 4) in drug-induced situations. The profiles of these subtypes strongly suggest that these osteoclasts belong to a heterogeneous cell population, namely, a diverse macrophage-associated cell type with bone catabolic and anabolic functions that are dependent on both local and systemic parameters. Further insight into these osteoclast subtypes may be important for understanding cell-cell communication in the bone microenvironment, treatment effects, and ultimately bone quality.