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ID PMID Title PublicationDate abstract
20960435 Breaking communication barriers for RA patients of South Asian origin: the use of a biling 2011 Mar BACKGROUND: People from the Indian subcontinent represent one of the largest ethnic groups in the UK. Patient education resources are required to address language barriers, poor literacy and (potentially discordant) cultural beliefs. We have investigated a novel strategy to meet this need. METHODS: Rheumatoid arthritis (RA) patients of South Asian origin who prefer to communicate in a South Asian language were invited to a face-to-face interaction with a trained patient volunteer to provide linguistically appropriate peer support and education, and given a bilingual educational audio CD. Qualitative methods were used to assess this approach; three focus groups were held and 15 patients participated in total. RESULTS: Four important themes were identified: (1) The need for information about RA; all patients agreed that this was vital to learn how to live with their chronic disease. (2) Currently available approaches to education; particular concerns related to a lack of time in clinic, language barriers, difficulties in communicating via interpreters and that most written information was available only in English. (3) Support provided by a trained patient volunteer; patients appreciated that they were listened to, and were motivated by the volunteers' positive attitude. (4) The usefulness of the audio CD; patients appreciated that information was presented in a language they could understand, via a convenient medium and which offered a helpful perspective on their illness. CONCLUSIONS: This approach is a successful way of delivering information and encouraged patients from a difficult-to-reach community to become more involved in their disease management.
20857157 Synovial fluid β-endorphin level in avascular necrosis, rheumatoid arthritis, and osteoar 2011 Apr The goal of this study is to determine and compare the β-endorphin levels in the synovial fluid of patients with different joint disorders (avascular necrosis, AVN; osteoarthritis, OA; and rheumatoid arthritis, RA of the hip or knee). Eighty-seven patients were involved in our study with an average age of 62 years. Thirty-three patients had AVN (18 hips, 15 knees). Twenty-three patients were diagnosed with OA (14 hips, 9 knees), and 31 patients suffered from RA (12 hips, 19 knees). We measured the β-endorphin levels of the synovial fluids -harvested from surgery-with radioimmunoassay. No significant difference was found in the β-endorphin levels of the synovial fluid from AVN comparing to OA and RA, however β-endorphin level was significantly higher in RA group than among patients with OA (p = 0.01). Synovial β-endorphin level was slightly lower in knee comparing to hip joint p = (0.06). When examining the different joints separately in compliance with diagnoses, we concluded that the synovial β-endorphin level from AVN was between the values of OA and RA without significant difference, whereas it was significantly higher in the knee of RA, than of OA groups (p = 0.05 knee, p = 0.2 hip). Our results confirmed those experiments which stated that there is a significant increase in synovial β-endorphin level in patients with inflammatory autoimmune diseases (e.g., RA), comparing to the level measured in degenerative conditions (e.g., OA).
22264971 Development of a composite questionnaire, the valuation of lost productivity, to value pro 2012 Jan OBJECTIVE: Existing productivity questionnaires do not capture sufficient information to enable the proper valuation of an individual's productivity loss to a society. The purpose of this article is to develop a questionnaire that captures the time lost from work due to a health problem and job and workplace characteristics so that the value of productivity loss to society can be calculated. METHODS: First, a questionnaire battery was developed by selecting items from existing productivity questionnaires. Next, items with similar content were identified and duplications were eliminated. Third, the draft questionnaire's feasibility was pretested in a focus group (n = 15). Finally, after appropriate refinements, its applicability was tested in 140 employed patients with rheumatoid arthritis recruited from a cohort in the United Kingdom. Multipliers relating the wage to marginal productivity were also derived using the questionnaire. RESULTS: The final questionnaire includes items on employment status; absenteeism; presenteeism; unpaid work; and job characteristics, which includes questions on team dynamics, availability of substitutes and their substitutability, time sensitivity, and compensation mechanisms. The importance of incorporating these questions demonstrated that when one employee was absent, or present at work but unable to work at full capacity, the consequent output loss could exceed the output of the employee alone. Multipliers were shown to be greater than one and represented the excess output loss. CONCLUSIONS: The new questionnaire enabled the job and workplace characteristics to be captured so that the actual productivity loss at the societal level attributable to absenteeism and presenteeism could be valued.
22292513 Kinematic analysis of sit to stand by persons with rheumatoid arthritis supported by a ser 2012 PURPOSE: The objective of this study was to quantify the kinesiological effect of the assistance provided by service dogs on transferring from sit to stand in persons with rheumatoid arthritis (RA). METHODS: Twenty-four participants performed a total of eight experimental transfers of sit to stand, including unassisted transfers, transfers with a cane and transfers with assistance from a service dog. We analysed movements at the lower extremity joints using a three-dimensional kinematics system and two force plates. RESULTS: At the hip joints, the range of motion changes and energy expenditure with a cane and with the service dog were smaller than that of the unassisted transfers. Transfers with a service dog resulted in less joint movement and less energy used in movements at the knee and ankle joints; participants also scored themselves as requiring less effort on a self-rating scale than in the other conditions. CONCLUSION: A service dog provides benefits in assisting with transfers from sit to stand by persons with RA. Future studies should consider training the service dogs to assume correct positions and use appropriate timing to support their partners during these transfers.
23247552 Debridement of painful forefoot plantar callosities in rheumatoid arthritis: the CARROT ra 2013 May The objective of this study was to evaluate the long-term benefits of sharp scalpel debridement of painful forefoot plantar callosities in rheumatoid arthritis (RA). The null hypothesis: sharp scalpel debridement would offer no additional long-term advantage in terms of pain and function. Sixty-five people with RA were randomised to receive regular sharp scalpel debridement of painful forefoot plantar callosities in conjunction with a combined therapeutic approach or a combined therapeutic approach alone. The primary outcome measure was change at 18 months in participant-reported forefoot plantar pain measured by a 100-mm visual analogue scale (VAS). Secondary outcome measures were recorded at baseline and study exit and included revised Foot Function Index, Health Assessment Questionnaire, Foot Impact Scale and gait parameters. At 18 months, there were no differences between groups for the primary outcome VAS-measured forefoot plantar pain (left foot (F = 0.23, p = 0.635), right foot (F = 2.14, p = 0.148)). Within-group changes were highly significant (treatment arm, difference = 16.9 (95 % confidence interval (CI) 9.4, 24.4), t = 4.6, p < 0.0001; control arm, difference = 17.5 (95 % CI 9.4, 25.5), t = 4.4, p < 0.0001). There was little change in scores of overall function and foot impact in either group and there were no significant changes in gait parameters noted. The long-term effects of sharp scalpel debridement of painful forefoot plantar callosities in people with RA, when used in conjunction with a combined therapeutic approach, produced no additional benefit over the combined therapeutic approach alone. Trial registration http://www.controlled-trials.com/ISRCTN05190231.
22589376 Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a 2013 Mar OBJECTIVES: CCX354-C is a specific, orally administered antagonist of the C-C chemokine receptor 1, which regulates migration of monocytes and macrophages to synovial tissue. This clinical trial evaluated the safety and efficacy of CCX354-C in patients with rheumatoid arthritis (RA). METHODS: CARAT-2 is a 12-week double-blind, randomised, placebo controlled trial in 160 patients with RA, with 68 tender joint count and 66 swollen joint count ≥8 and C-reactive protein (CRP) >5 mg/l, despite being on methotrexate for at least 16 weeks. Subjects received placebo, CCX354-C 100 mg twice daily, or 200 mg once daily for 12 weeks. Endpoints included safety (primary) and RA disease activity assessments based on American College of Rheumatology (ACR) response, and changes in 28-joint disease activity score-CRP, individual ACR components, as well as soluble bone turnover markers. RESULTS: CCX354-C was generally well tolerated by study subjects. The ACR20 response at week 12 was 39% in the placebo group, 43% in the 100 mg twice daily group (difference and 95% CI compared with placebo, 4.5 (-14.1 to 23.1); p=0.62) and 52% in the 200 mg once daily group (13.0 (-5.8 to 31.8); p=0.17) in the intention-to-treat population, and 30% in the placebo group, 44% in the 100 mg twice daily group (14.4 (-5.9 to 34.8); p=0.17), and 56% in the 200 mg once daily group (25.8 (5.3 to 46.4); p=0.01) in the prespecified population of patients satisfying CRP and joint count eligibility criteria at the screening and day 1 (predose) visits. CONCLUSIONS: CCX354-C exhibited a good safety and tolerability profile and evidence of clinical activity in RA.
21289424 [Animal models for bone and joint disease. Osteoimmunology and animal models for rheumatoi 2011 Feb Bone homeostasis is maintained by not only bone cells but also by various types of cells. Particularly, the skeletal system has an apparent relationship with the immune system, in that immune cells are generated in the bone marrow and that osteoclasts which play a crucial role in bone destruction differentiate from monocyte/macrophage lineage cells. In addition, investigation into rheumatoid arthritis (RA) has highlighted the relevance of the interplay between the bone and immune systems and promoted a new research field of 'osteoimmunology'. Here, we summarize how various animal models for RA contributed, and can contribute to the progress in osteoimmunology and increasing understanding of RA development and treatment.
21295595 A powerful truncated tail strength method for testing multiple null hypotheses in one data 2011 May 21 In microarray analysis, medical imaging analysis and functional magnetic resonance imaging, we often need to test an overall null hypothesis involving a large number of single hypotheses (usually larger than 1000) in one dataset. A tail strength statistic (Taylor and Tibshirani, 2006) and Fisher's probability method are useful and can be applied to measure an overall significance for a large set of independent single hypothesis tests with the overall null hypothesis assuming that all single hypotheses are true. In this paper we propose a new method that improves the tail strength statistic by considering only the values whose corresponding p-values are less than some pre-specified cutoff. We call it truncated tail strength statistic. We illustrate our method using a simulation study and two genome-wide datasets by chromosome. Our method not only controls type one error rate quite well, but also has significantly higher power than the tail strength method and Fisher's method in most cases.
21459946 Cognitive dysfunction in patients with systemic lupus erythematosus: a controlled study. 2011 Jun OBJECTIVE: To determine the extent to which cognitive dysfunction (CD) observed in patients with systemic lupus erythematosus (SLE) exceeds that seen in a matched control group of patients with rheumatoid arthritis (RA), and to estimate the prevalence of CD in SLE in a community-based sample. METHODS: A random subsample of 31 patients with SLE was compared to patients with RA matched by age, sex, and race and derived from the same patient population. Cognitive function was assessed by the Automated Neuropsychological Assessment Metrics (ANAM). The primary outcome was the total throughput score (number of correct responses divided by the time taken for those responses averaged over all subtests), adjusted for premorbid intelligence, neuromuscular efficiency, disease activity, damage, depression, fatigue, and health-related quality of life. RESULTS: There were no statistically significant differences in mean throughput scores between patients in the SLE and RA groups in any subtest of the ANAM or in the total throughput score. The frequency of CD, defined as either total scores > 1.5 SD below the mean of the RA population, or 4 or more ANAM subtests each > 1.5 SD below the RA mean, was similar in patients with SLE and in RA controls. CONCLUSION: We found no differences in cognitive function between patients with SLE and RA, suggesting that the CD found in some patients with SLE may represent the consequences of a chronic and/or inflammatory disease rather than SLE-related central nervous system damage.
22580113 MRI-assessed therapeutic effects of locally administered PLGA nanoparticles loaded with an 2012 Aug 10 Rheumatoid arthritis is characterized by systemic inflammation of synovial joints leading to erosion and cartilage destruction. Although efficacious anti-tumor necrosis factor α (TNF-α) biologic therapies exist, there is an unmet medical need for safe and more efficient treatment regimens for disease remission. We evaluated the anti-inflammatory effects of poly(dl-lactide-co-glycolide acid) (PLGA) nanoparticles loaded with small interfering RNA (siRNA) directed against TNF-α in vitro and in vivo. The siRNA-loaded PLGA nanoparticles mediated a dose-dependent TNF-α silencing in lipopolysaccharide-activated RAW 264.7 cells in vitro. The severity of collagen antibody-induced arthritis in DBA/1J mice was assessed by paw scoring and compared to the degree of magnetic resonance imaging (MRI)-quantified joint effusion and bone marrow edema. Two intra-articular treatments per joint with nanoparticles loaded with TNF-α siRNA (1 μg) resulted in a reduction in disease activity, evident by a significant decrease of the paw scores and joint effusions, as compared to treatment with PLGA nanoparticles loaded with non-specific control siRNA, whereas the degree of bone marrow edema in the tibial and femoral head remained unchanged. When the siRNA dose was 5 or 10 μg, there was no difference between the specific and the non-specific siRNA treatment groups. These findings suggest that MRI is a promising method for evaluation of early disease progression and treatment in murine arthritis models. In addition, proper siRNA dosing seems to be important for a positive therapeutic outcome in vivo. However, further studies are needed to fully clarify the mechanism(s) underlying the observed anti-inflammatory effects of the siRNA-loaded nanoparticles.
21789615 Osteoprotegerin expression in bone marrow by treatment with tocilizumab in rheumatoid arth 2012 Sep The aim of this study was to investigate histological changes of bone marrow in response to tocilizumab for rheumatoid arthritis (RA). After tocilizumab therapy, bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty (TKA). Control samples were obtained from ten RA patients who underwent MTX mono-therapy. Histological examination of structural differences between the tocilizumab and control groups in bone marrow was performed using hematoxylin and eosin (H&E) to evaluate differences. In immunohistochemical examination, the expression of seven molecules including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), CD68, osteoprotegerin (OPG), receptor activator of nuclear kappa B ligand (RANKL), CD4 and osteopontin (OPN) were compared between two groups. NTx was significantly low at 44.5 ± 2 nM BCE/mM Cr compared with control at 73.2 ± 8 nM BCE/mM Cr. Immunohistochemical examination revealed that the bone marrow tissues of the RA patients who underwent tocilizumab therapy demonstrated significant positive OPG as compared with the control. However, immunohistochemical examinations after tocilizumab revealed that TNF-α, IL-6, CD68, CD4, OPN and RANKL were not significantly different with control of MTX in bone marrow. Therefore, treatment with tocilizumab increased the expression of OPG as the histological changes with respect to inhibit RANKL-related bone resorption of bone marrow in RA.
20852002 Integrated population pharmacokinetics of etanercept in healthy subjects and in patients w 2011 Jun Etanercept pharmacokinetics in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriasis were assessed separately with distinct models using population pharmacokinetics methods of limited precision. The different model structures and associated significant covariates identified by these earlier methods made it difficult to compare etanercept pharmacokinetics among disease groups. This integrated analysis aimed to establish a framework to evaluate previously established population pharmacokinetic models of etanercept, and to identify consistent and important demographic and disease factors that affected etanercept pharmacokinetics in a diverse population of healthy subjects and patients with RA and AS. In this integrated analysis, cumulative rich and sparse etanercept concentration data from 53 healthy volunteers, 212 patients with RA, and 346 patients with AS were examined and compared using nonlinear mixed effect methodology implemented the in NONMEM VI software package. A more precise estimation method (FOCEi) was employed and compared with the first-order method in population pharmacokinetics model building and evaluation. The integrated analysis found that an optimal population pharmacokinetics model with a 2-compartment structure adequately characterized etanercept pharmacokinetics in all subject groups. Health status or disease type did not significantly affect etanercept pharmacokinetics. In adult patients with RA and AS, age and body weight do not significantly affect etanercept pharmacokinetics.
21847747 The impact of MRI on the clinical management of inflammatory arthritides. 2011 Sep In the past two decades, MRI has gained a major role in research and clinical management of patients with inflammatory arthritides, particularly in spondyloarthritis (SpA), rheumatoid arthritis (RA), and osteoarthritis (OA). MRI is regarded as the most sensitive imaging modality for detecting early SpA in young patients with inflammatory back pain and normal radiographs of the sacroiliac joints. The recently published Assessment of SpondyloArthritis International Society classification criteria for axial SpA include for the first time a positive MRI demonstrating sacroiliitis as an imaging criterion indicative of SpA together with at least one clinical feature of SpA. Recent data show that systematic assessment of sacroiliitis displayed on MRI has much greater diagnostic utility than previously reported and highlight the diagnostic relevance of structural lesions. In RA, MRI has predictive value for the development of disease in new onset undifferentiated arthritis, and MR pathology at disease onset is a highly significant predictor of radiographic erosions. Consequently MRI has been credited with an important role in the new ACR/EULAR 2010 classification criteria for RA. In OA, bone marrow edema (BME) and synovitis may serve as biomarkers in interventional trials. Treatment interventions targeting BME and synovitis observed on MRI in inflammatory arthritides may have a disease-modifying effect as these lesions are potentially reversible and have been shown to be associated with structural progression. Research should focus on the prognostic significance of MRI lesions in larger cohorts and whether adding MRI to routine care improves clinical and radiographic outcome in patients with inflammatory arthritides.
22484803 Lactobacillus rhamnosus exopolysaccharide ameliorates arthritis induced by the systemic in 2012 Jun Oral administration of some probiotic bacteria (e.g. Lactobacillus rhamnosus) attenuates various types of experimental arthritis, including collagen-induced arthritis (CIA) and inhibits arthritogenic autoantibodies. Much less is known about the possible anti-arthritogenic properties of exopolysaccharide (EPS), the major component of lactic bacteria biofilm. In this study, we asked the question whether systemic administration of EPS derived from L. rhamnosus KL37 depresses the production of anti-collagen IgG and affects the development of CIA in DBA/1 mice. Arthritis was induced employing two models of active CIA, in which mice were immunized with type II collagen (CII) either in the presence of lipopolysaccharide (LPS; mild arthritis with moderate CII-specific IgG production) or with Complete Freund's Adjuvant and LPS (severe arthritis with massive CII-specific IgG production). Passive CIA was induced by intravenous injection of CII-specific monoclonal antibodies and LPS. Disease progression, the incidence and severity of arthritis, were determined. Serum concentration of CII-specific IgG was measured by enzyme-linked immunosorbent assay. Systemic administration of EPS markedly reduced CII-specific antibody production. Moreover, EPS significantly ameliorated arthritis in the active models of CIA, especially, when LPS alone was used as an adjuvant. In contrast, when arthritogenic antibodies were injected to mice in high amounts, the effect of EPS on the development of passive CIA was negligible and transient. These results show that EPS can suppress active CIA by the inhibition of arthritogenic antibodies production. Therefore, we suggest that EPS or EPS-producing probiotics may be promising agents for the supporting therapy of patients with rheumatoid arthritis.
20373059 Golimumab and malignancies: true or false association? 2011 Jun Malignancy is one of the comorbidities linked to golimumab, a biological TNF-α blocker. In this systematic review and meta-analysis, we searched different databases and analyzed original publications to elucidate the remaining open question about the real association of malignancies with golimumab therapy. The most frequent cancer in patients treated with golimumab, in association or not with methotrexate, is the lung adenocarcinoma. However, lymphoma is not very commonly represented in these patients. We show that there is no major and evident risk of malignancies associated with golimumab in current scientific literature. An increased risk of malignancies may be associated with golimumab, but this warrants further clinical confirmation. Also, this risk mentioned in different studies must be taken with caution because of number of limits and biases.
21953341 Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte a 2012 Mar BACKGROUND: Histone deacetylase inhibitors (HDACi) display potent therapeutic efficacy in animal models of arthritis and suppress inflammatory cytokine production in rheumatoid arthritis (RA) synovial macrophages and tissue. OBJECTIVES: To determine the molecular mechanisms contributing to the suppressive effects of HDACi on RA synovial cell activation, using interleukin 6 (IL-6) regulation as a model. METHODS: RA fibroblast-like synoviocytes (FLS) and healthy donor macrophages were treated with IL-1β, tumour necrosis factor (TNF)α, lipopolysaccharide or polyinosinic:polycytidylic acid (poly(I:C)) in the absence or presence of the HDACi trichostatin A (TSA) or ITF2357 (givinostat). IL-6 production and mRNA expression was measured by ELISA and quantitative PCR (qPCR), respectively. Protein acetylation and the activation of intracellular signalling pathways were assessed by immunoblotting. The DNA-binding activity of nuclear factor κB (NFκB) and activator protein 1 (AP-1) components was measured by ELISA-based assays. RESULTS: HDACi (0.25-1.0 μM) suppressed RA FLS IL-6 production induced by IL-1β, TNFα and Toll-like receptor ligands. Phosphorylation of mitogen-activated protein kinases and inhibitor of κBα (IκBα) following IL-1β stimulation were unaffected by HDACi, as were AP-1 composition and binding activity, and c-Jun induction. TSA induced a significant reduction in nuclear retention of NFκB in FLS 24 h after IL-1β stimulation, but this did not reduce NFκB transcriptional activity or correlate temporally with reductions in IL-6 mRNA accumulation. HDACi significantly reduced the stability of IL-6 mRNA in FLS and macrophages. CONCLUSIONS: Our study identifies a novel, shared molecular mechanism by which HDACi can disrupt inflammatory cytokine production in RA synovial cells, namely the promotion of mRNA decay, and suggests that targeting HDAC activity may be clinically useful in suppressing inflammation in RA.
22045973 Quality of life in patients with immune-mediated inflammatory diseases. 2011 Nov There is no doubt that patients with immune-mediated inflammatory diseases (IMID) have a significantly impaired quality of life (QOL). Pain and disability often leave these patients helpless and frustrated. The recognition that addressing physical and psychological functioning plays a significant role in an overall treatment approach led to the inclusion of QOL measures as secondary outcomes in clinical trials with IMID patients. To that end, both generic and disease-specific instruments have been utilized. Measurement of health-related QOL (HRQOL) and patient-reported outcomes (PRO) in a controlled manner allows for better understanding of the correlation between different aspects of disease activity and QOL. In addition, the effects of different therapeutic options on HRQOL-related outcomes can be further evaluated. This 3-part section describes key QOL-related complaints of patients with IMID affecting joints, skin, or gut. An overview of the strengths and weaknesses of various commonly used HRQOL instruments is provided. Finally, the influence of anti-tumor necrosis factor-α agents on HRQOL outcomes, as assessed in recent clinical trials, is highlighted.
21625887 Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis. 2011 Dec The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity. INTRODUCTION: RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption. METHODS: Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, β-isomerised carboxy-terminal telopeptide of type 1 collagen [βCTX] and osteoprotegerin [OPG]). RESULTS: A significant decrease in bone resorption was observed 6 months after rituximab (median change βCTX -50 ng/L, 95%CI -136, -8 p < 0.001, this equates to -37%; 95%CI -6, -49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 μg/L, 95%CI -1.0, 11.2, p = 0.02; 13%; 95%CI -3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of βCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r (s) = 0.570, p = 0.014). CONCLUSIONS: In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.
21144590 The potential role of VPREB1 gene copy number variation in susceptibility to rheumatoid ar 2011 Jun Although the etiology of rheumatoid arthritis (RA) remains unknown, it has been widely suggested that RA has a genetic background. In humans, a copy number loss of 22q11.2, a region harboring the VPREB1 gene, has been suggested to be associated with several immunologic disorders, but there has been no study on the copy number variation (CNV) of the VPREB1 and its potential association with RA. Here, we explored the association between the RA and the CNV of the VPREB1 gene by performing genomic quantitative PCR and quantification of B cell subsets in RA patients and controls. The proportion of the individuals with <2 copies of the VPREB1 gene was significantly higher in the patient group than that in the controls (12.9% vs 0.9%, p<0.0001), while that of the individuals with >2 copies was lower in the patient group than that in the controls (1.7% vs 18.9%, p<0.0001). The odds ratio (OR) of the individuals with <2 copies was significantly higher compared with the odds ratio of those individuals with 2 copies (OR=12.1, 95% confidence interval (CI) 2.8-51.6). Likewise, the OR of the individuals with >2 copies was significantly lower than the OR of those individuals with 2 copies (OR=0.09, 95% CI 0.03-0.3). We also found that the proportion of CD21⁻CD23⁻ B cells was significantly higher in the RA patients compared with that of the controls (11.9% vs 5.7%, p=0.002), but the proportion of CD21+CD23+ cells was significantly lower in the RA patients (26.2% in RA vs 34.9% in the controls, p=0.005). To the best of our knowledge, this is the first evidence showing the association between a low copy number of the VPREB1 gene and RA, and this may help understanding the pathogenesis of RA and other autoimmune disorders.
21182357 Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons appr 2011 Jan STUDY OBJECTIVE: To compare the efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) versus placebo with or without methotrexate, in treating rheumatoid arthritis. DESIGN: Comparative effectiveness analysis using an indirect treatment comparison (ITC) method in a Bayesian framework. PATIENTS: Adults with rheumatoid arthritis who had been enrolled in randomized controlled trials (RCTs) and had never failed biologic DMARD therapy. MEASUREMENTS AND MAIN RESULTS: Two random-effects logistic regression models, representing 6 and 12 months of treatment, were created using RCTs identified in a literature search. Twenty-three RCTs (11,589 patients) were included in the 6-month model and 10 RCTs (6051 patients) in the 12-month model. Nine biologic DMARDs in five therapeutic drug classes were included in the 6-month model, and six biologic DMARDs in three classes were included in the 12-month model. Our efficacy end point was the American College of Rheumatology 50% improvement criteria. In the 6-month model, all biologic DMARDs and methotrexate were significantly more efficacious than placebo and ranked in the following order: certolizumab (median log odds ratio [OR] 2.6), tocilizumab (1.7), rituximab (1.6), infliximab (1.6), etanercept (1.4), adalimumab (1.4), golimumab (1.4), abatacept (1.2), anakinra (1.0), and methotrexate (0.8). Of 45 pairwise comparisons, certolizumab was significantly more efficacious than methotrexate, but no other comparisons were significant. The rank order in the 12-month analysis was certolizumab (median log OR 2.0), rituximab (2.0), adalimumab (1.4), infliximab (1.4), etanercept (0.9), abatacept (0.6), and methotrexate (0.8). Of the 21 pairwise comparisons, none were significant. The results of the model using therapeutic class revealed that each class was more efficacious than placebo. In pairwise comparisons, each class was more efficacious than methotrexate, but none was more efficacious than another. CONCLUSION: Use of emerging ITC methods enabled us to compare the efficacy of biologic DMARDs for the treatment of rheumatoid arthritis in the absence of direct head-to-head comparison trials. Our methods enabled us to rank order these treatments. Further analyses by drug and by therapeutic class suggest that biologic DMARDs are similarly efficacious.