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ID PMID Title PublicationDate abstract
27770831 Association of anti-peptidyl arginine deiminase antibodies with radiographic severity of r 2016 Oct 22 BACKGROUND: Evidence suggests that the presence of peptidyl arginine deiminase type 4 (PAD4) antibodies is associated with radiographic-severity rheumatoid arthritis (RA) among Caucasian patients. The presence of anti-PAD4 antibodies that were cross-reactivity against PAD3 was associated with more aggressive erosive disease (compared with the presence of anti-PAD4 antibodies without anti-PAD3 crossreactivity) in Caucasian RA patients. The objectives of this study were to determine the prevalence of serum anti-PAD4 and anti-PAD4/PAD3 cross-reactive autoantibodies in African Americans with RA and whether these antibodies associate with radiographic severity and radiographic progression. METHODS: Serum anti-PAD4 and anti-PAD4/PAD3 antibodies were measured by immunoprecipitation, and the temporal trends in titers were analyzed. We compared total radiographic scores among anti-PAD4-positive, anti-PAD4/PAD3-positive, and anti-PAD4-negative patients and used a zero-inflated negative binomial model to determine associations between radiographic severity and antibody status. Logistic regression was used to analyze radiographic progression. RESULTS: Of 192 African-American patients with RA, 73 % were anti-citrullinated peptide/protein antibody (ACPA)-positive, 46 out of 192 (24 %) of whom had serum anti-PAD4 antibodies. Median (interquartile range) total Sharp van der Heijde radiographic scores were 2 (1-97.5) in ACPA-positive patients and 0 (0-3) in ACPA-negative patients (P < 0.001). Of the 46 anti-PAD4-positive patients, 20 had anti-PAD4 antibodies that cross-reacted with PAD3. In patients with early RA, anti-PAD4 and anti-PAD4/PAD3 antibody titers increased over time (P = 0.006, P = 0.001, respectively). Median (interquartile range) total radiographic scores were higher for anti-PAD4-positive than for anti-PAD4-negative patients (3 (1-115) versus 2 (0-11), respectively; P = 0.005). Median (interquartile range) total radiographic score for anti-PAD4/PAD3-positive patients was 76 (3-117) (P < 0.001) versus anti-PAD4-negative patients. Only anti-PAD4/PAD3 antibodies associated with radiographic severity (incidence rate ratio = 2.81; 95 % confidence interval 1.23, 6.43). CONCLUSION: This analysis suggests that autoantibodies against PAD4 and PAD3 proteins may serve as biomarkers for identifying African-American patients with RA and higher radiographic severity.
26382579 Modified metacarpal shortening osteotomy of the midcarpal bone for preserving metacarpopha 2016 Recent advances in medication choices have strikingly improved the management of rheumatoid arthritis. However, medication alone cannot place back already deformed joints. Thus, to prevent metacarpophalangeal (MP) joint destruction, joint deformity correction should be considered since mechanical stress induced by finger motions will eventually destruct the undestructed joint, with a possibility of recurrence and future implant arthroplasty in mind since RA still remains as a progressive disease. We report a modified metacarpal shortening osteotomy for correcting MP joint deformity. The advantage of our technique over previous osteotomies is that it easily allows for subsequent implant arthroplasty even after the recurrence of joint deformity/destruction. Major modifications include that the metacarpal is shortened at its mid-shaft and the osteotomy is performed vertical to the shaft and fixed with surgical wiring. We believe that combination therapy consisting of medication and surgery is preferable to prevent joint destruction, even in this age of biological agents.
25605045 Does combined clinical and ultrasound assessment allow selection of individuals with rheum 2015 May OBJECTIVE: To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti-tumor necrosis factor (anti-TNF) therapies. METHODS: As part of a real-world approach, patients with RA receiving anti-TNF therapies were reviewed in a dedicated biologic therapy clinic. Patients not taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28) remission (≤2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months were invited to reduce their anti-TNF therapy dose by one-third. RESULTS: Between January 2012 and February 2014, a total of 70 patients underwent anti-TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at 3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months followup. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS ≤1 at 6 months. The addition of PDUS identified 8 patients (25% of those that flared) in DAS28 remission, with subclinically active disease. Those who maintained dose reduction were more likely to be rheumatoid factor (RF) negative (46% versus 17%; P = 0.03) and have lower DAS28 scores at biologic therapy initiation (5.58 versus 5.96; P = 0.038). CONCLUSION: Combined clinical and US assessment identifies individuals in remission who may be suitable for anti-TNF dose reduction and enhances safe monitoring for subclinical disease flares. Despite longstanding severe RA, a subset of our cohort sustained prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF status appeared predictive of sustained remission.
27191345 Cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis f 2016 Jul OBJECTIVES: The aim of this study was to calculate the marginal cost of dose escalation in people with rheumatoid arthritis treated with tumour necrosis factor (TNF) inhibitors across Europe. METHODS: The proportion of people who escalate their dose of TNF inhibitor and the average percentage increase in TNF inhibitor cost associated with escalators versus non-escalators was calculated from previously published estimates, weighted by the sample size for each study. The number of people with rheumatoid arthritis treated with TNF inhibitors and the corresponding total drug sales were obtained for five European countries from Decision Resources' Pharmacor Market Forecast. Method 1 assumed that total sales of a TNF inhibitor represented the cost of an escalator multiplied by the number of escalators plus the cost of a non-escalator multiplied by the number of non-escalators. Method 2 assumed that the drug cost per day used to forecast total sales was calculated using the dose of TNF inhibitor used by non-escalators. The marginal cost of TNF inhibitor dose escalation was estimated by multiplying the difference in cost between escalators and non-escalators by the number of escalators. RESULTS: The estimated increase in TNF inhibitor costs associated with dose escalation in people with rheumatoid arthritis across five European countries (Germany, France, UK, Spain and Italy) was €51.5-54.4 million for adalimumab, €44.8-52.8 million for infliximab and €5.8-5.9 million for etanercept. CONCLUSIONS: Dose escalation of the TNF inhibitors adalimumab, etanercept and infliximab in people with rheumatoid arthritis has resulted in an increase in TNF inhibitor costs across five European countries.
27020783 Total knee replacement with tibial tubercle osteotomy in rheumatoid patients with stiff kn 2016 Nov PURPOSE: Total knee arthroplasty (TKA) is a well-proven modality that can provide pain relief and restore mobility for rheumatoid arthritis (RA) patients with advanced joint destruction. Patellar ligament avulsion, especially in presence of poor bone quality and knee stiffness, is one of the special considerations that must be addressed in this unique population of patients. This study aimed to determine the functional results in a series of rheumatoid patients with stiff knee and end-stage joint destruction who underwent tibial tubercle osteotomy during TKA. METHODS: Twenty-three knees in 20 patients (16 women; four men) at a mean age of 54 years with end-stage arthritis and knee stiffness due to RA were operated upon for TKA using tibial tubercle osteotomy as a step during the operation. Patients were reviewed clinically and radiographically with a minimum follow-up of two years. Complications were noted. Hospital for Special Surgery (HSS) score was recorded pre-operatively and at six and 12 months postoperatively. RESULTS: Union occurred at the osteotomy site in 21 of 23 cases. One case had deep venous thrombosis (DVT). There was no infection or periprosthetic fracture, and at last follow-up, no patient required revision. HSS score improved from 46 (15-60) pre-operatively to 85 (71-96) post-operatively. CONCLUSION: Tibial tubercle osteotomy during TKA in patients with RA and stiff knee is technically demanding yet proved to be effective in improving post-operative range of movement and minimising the complication of patellar ligament avulsion.
26808075 Coexistence of ischemic heart disease and rheumatoid arthritis patients-A case control stu 2016 Apr BACKGROUND: Over the last few decades, several studies have demonstrated the connection between Rheumatoid Arthritis (RA) and Ischemic Heart Disease (IHD). The additional risk for RA patients to also suffer from IHD varies based on the definition of the diseases in question, the populations evaluated, and the variables included in the studies. OBJECTIVES: To quantify the association between RA and IHD according to certain demographics as well as traditional cardiovascular risk factors in order to determine their roles in the development of coronary artery disease among patients with RA. METHODS: Using data from the largest HMO in Israel, the Clalit Health Services, we selected for patients with RA. These patients were compared with age and sex matched controls with regards to the prevalence of IHD in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. RESULTS: The study included 11,782 patients with RA and 57,973 age and sex matched controls. The prevalence of IHD in patients with RA was increased compared with the prevalence in controls (16.6% and 12.8% respectively, P<0.001). In a multivariate analysis, RA was associated with higher proportions of IHD (OR 1.346, 95% confidence interval 1.255-1.431).
26690891 Association of homocysteine with immunological-inflammatory and metabolic laboratory marke 2015 Nov OBJECTIVES: The increase of homocysteine (Hcy) is an independent risk factor related to the development of atherosclerosis (AS) and the cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Cardiovascular disease is a leading cause of mortality in RA. The aim of the study was to determine its relationship with homocysteine and the clinical immunological-inflammatory and metabolic laboratory markers and evaluate the factors in relation to hyperhomocysteinaemia in RA. METHODS: Analysis of total serum homocysteine (Hcy) concentrations was carried out in fifty patients with RA compared with 50 matched health controls. In patients with RA, numerous immunological-inflammatory and metabolic laboratory makers included, folate, vitamin B12 complement (i.e. C3 and C4), C-reactive protein (CRP), Rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibody, cystatin C (CysC), triglycerides, cholesterol and total leukocyte count. We also assessed imaging makers, common carotid intima-media thickness (IMT) and disease activity makers such as Disease Activity Score in 28 joints (DAS28). RESULTS: Median concentration of Hcy was significantly greater in patients with RA than in controls: 9.09 (5.38-33.91) vs. 7.45 (4.89-25.77) μmol/L (p<0.001). In RA patients, homocysteine was inversely associated with folate (rho=-0.672, p<0.0001), vitamin B12 (rho=-0.424, p=0.002), C3 (rho=-0.612, p<0.0001), C4 (rho=-0.323, p=0.022), correlate with CRP (rho=0.342, p=0.015), CysC (rho=0.430, p=0.002), but not with anti-CCP antibody (rho=0.205, p=0.152), RF (rho=0.214, p=0.135), triglycerides (rho=-0.107, p=0.459), cholesterol (rho=0.160, p=0.268), total leukocyte count (rho=-0.157, p=0.276), IMT (rho=0.134, p=0.156), DAS28 (rho=0.211, p=0.148). There was association between hyperomocysteinaemia in RA with vitamin B12 (p=0.037), folate (p<0.001), and CRP (p=0.018). There was no association with male gender, anti-CCP antibody, RF, IMT and DAS28. CONCLUSIONS: Results from this study suggested that Hcy concentration was increased in RA patients and associated with RA-related immunological-inflammatory and metabolic laboratory markers, including folate, vitamin B12, CRP, CysC, C3, C4. Early determination of Hcy and correlated clinical laboratory markers may be useful to evaluate RA patients with high cardiovascular risk.
27919199 Predictive factors associated with the progression of large-joint destruction in patients 2017 Sep OBJECTIVE: To investigate the associations between large-joint damage and findings on fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) using the "assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging (ARASHI)" scoring system. METHODS: A total of 270 large joints (shoulders, elbows, hips, knees, and ankles) in 27 rheumatoid arthritis patients were assessed. FDG-PET/CT was performed at the initiation of biologics. Radiographs at baseline and at 3 years were evaluated using the ARASHI score. RESULTS: Radiographic progression of damage was detected in 35 by Larsen grade vs. 87 by the ARASHI score. The maximum standardized uptake value (SUVmax) at baseline, Steinbrocker stage at baseline, concomitant prednisolone use, and disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at 6 months were significantly higher in the radiographic progression group. An SUVmax higher than 1.65 at baseline was a significant predictive factor for progressive damage at 3 years. CONCLUSIONS: The ARASHI score may allow more detailed evaluation of large joints than the Larsen method. Joint destruction is likely to have progressed at 3 years in large joints, which had a higher SUVmax at the initiation of biologics.
26741702 Interface Management between General Practitioners and Rheumatologists-Results of a Survey 2016 OBJECTIVE: To measure the views of general practitioners (GPs) and rheumatologists in a nationwide evaluation, so as to optimise their cooperation in managing patients with inflammatory rheumatic diseases. METHODS: A questionnaire covering aspects of collaboration was sent, both by mail and/or by email, to all GPs and rheumatologists in Austria. Topics covered were (i) examinations and interventions to be performed before referral, (ii) the spectrum of diseases to be referred, and (iii) the role of GPs in follow-up and continuous management of patients. RESULTS: 1,229 GPs of the 4,016 GPs (31%) and 110 of the 180 rheumatologists (61%) responded to the questionnaire. In cases of suspected arthritis, 99% of the GPs and 92% of the rheumatologists recommended specific laboratory tests, and 92% and 70%, respectively, recommended X-rays of affected joints before referral. Rheumatoid arthritis and spondyloarthritis, psoriatic arthritis and connective tissue disease were unanimously seen as indications for referral to a rheumatologist. Only 12% of rheumatologists felt responsible for the treatment of hand osteoarthritis and fibromyalgia. 80% of GPs and 85% of rheumatologists were of the opinion that treatment with disease-modifying drugs should be initiated by a specialist. Subsequent drug prescription and administration by GPs was supported by a majority of GPs and rheumatologists, with a concomitant rheumatologist follow-up every three to six months. CONCLUSION: The considerable consensus between the two professional groups constitutes a solid base for future joint recommendations, with the aim to accelerate the diagnostic process and the initiation of adequate therapy.
27215178 The signal transducer and activator of transcription factors lodge in immunopathogenesis o 2015 Dec 23 Rheumatoid arthritisis (RA) is a chronic autoimmune disorder that affects ~1-2% of the world's population and damages synovial joints. RA is characterized by inflammation, autoantibody production, cartilage and bone destruction and synovial hyperplasia. Inflammation induces systemic and articular synthesis of pro-inflammatory cytokines, such as tumor necrosis factor alpha and interleukin-6 that play essential roles in joint and other organ damage in this disease. Considering the role of signal transducer and activator of transcription factors (STATs) in signaling of these cytokines, these proteins may be involved in the pathogenesis of RA. The expression and activity of STATs can contribute to the onset, progression and severity of RA. All STAT family members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) have been associated with autoimmune diseases, as highlighted in several studies. In this review we aim to describe the immunobiology of STATs and its family members and the role of these proteins in the immunopathogenesis of RA.
26508503 Iguratimod in combination with methotrexate in active rheumatoid arthritis : Therapeutic e 2016 Oct BACKGROUND: Rheumatoid arthritis (RA) is a potentially destructive disease that may have a profound impact on patients' function and quality of life. RA therapy is still a challenge for rheumatologists; however, new antirheumatic drugs may be a treatment option for disease-modifying antirheumatic drug (DMARD)-experienced patients with active RA. OBJECTIVES: The present study is a prospective trial that aims to investigate the effects of therapy with iguratimod plus methotrexate (MTX) in comparison with iguratimod or MTX monotherapy in DMARD-experienced adult patients with active RA. METHODS: A total of 131 patients (24 men, 107 women, mean age 46.63 ± 10.61 years) with a history of being treated with traditional DMARDs were investigated. In all, 44 patients were treated with iguratimod (25 mg, twice daily, orally) plus MTX (a weekly dose of 10 mg, orally), 38 patients received iguratimod (25 mg, twice daily, orally), or 49 patients received MTX (weekly dose of 10 mg, orally) for 24 weeks. RESULTS: A therapeutic effect with iguratimod was observed between 4 and 10 weeks after treatment initiation and was effective even in patients who had a poor response to previous treatment with DMARDs. The combination of iguratimod with MTX was superior to iguratimod or MTX monotherapy. CONCLUSION: The data imply that iguratimod is a welcome addition to the small-molecule drug therapy for DMARD-experienced patients with active RA. Iguratimod (alone or in combination with MTX) is an emerging option for the treatment of DMARD-experienced adult patients with active RA who have had an inadequate response to or are intolerant of other DMARDs.
26883119 Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthriti 2016 Feb 16 BACKGROUND: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg × 2, but some data have suggested similar clinical efficacy with 500 mg × 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. METHODS: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. RESULTS: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg × 2 and 500 mg × 2, respectively. Patients treated with 500 mg × 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg × 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 ± SD -2.0 ± 1.3 (high dose) vs. -1.7 ± 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). CONCLUSIONS: In this large observational cohort initial treatment with RTX at 500 mg × 2 and 1000 mg × 2 led to comparable clinical outcomes at 6 months.
26842950 A randomised trial evaluating anakinra in early active rheumatoid arthritis. 2016 Jan OBJECTIVES: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. METHODS: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates. RESULTS: 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59). CONCLUSIONS: Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.
26248812 Periodontal pathogens participate in synovitis in patients with rheumatoid arthritis in cl 2015 Dec OBJECTIVE: The objective of this study was to investigate the role of periodontal pathogens in RA in remission. METHODS: Twenty-one patients with active RA and 70 patients in clinical remission, including 48 patients with synovitis [US power Doppler (USPD)(+) group] and 22 patients without synovitis [USPD(-) group] were clinically assessed by US. CRP, ESR, haemoglobin, MMP-3, RF and ACPA were measured. Antibody titres against four types of periodontal pathogen [Aggregatibacter actinomycetemcomitans, Eikenella corrodens (Ec), Porphyromonas gingivalis and Prevotella intermedia (Pi)] were analysed using ELISA. RESULTS: Musculoskeletal US examination showed that 68.6% of patients with RA in clinical remission exhibited synovitis. CRP, ESR, haemoglobin, MMP-3 and RF levels in both the USPD(+) and USPD(-) groups were clearly lower compared with the RA group in non-remission. The IgG serum antibody titre against Ec in the non-remission RA(+) group was significantly greater than that in the USPD(+) group, and the IgG antibody titre against Pi in the non-remission RA and USPD(+) groups was greater than in the USPD(-) group. CONCLUSION: More than half of RA patients in remission showed persistent synovitis. This synovitis may be associated with periodontal disease-causing Pi. Thus, treating periodontal disease should also be considered in order to achieve more profound remission of RA.
27236260 Gout and rheumatoid arthritis, both to keep in mind in cardiovascular risk management: A p 2017 Jan OBJECTIVES: To assess in one time window cardiovascular risks for both patients with gout and patients with rheumatoid arthritis in a Dutch primary care population. METHODS: Retrospective matched cohort study with data from the electronic health records of 51 Dutch general practices. Participants were patients aged 30 years or older with an incident diagnosis of gout (n=2655) or rheumatoid arthritis (n=513), and matched non-disease controls (n=7891 and n=1850 respectively). At disease incidence date, patients and controls were compared for prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and prior cardiovascular diseases. Patients without prior cardiovascular disease were followed for a first cardiovascular disease, and compared to controls using Kaplan-Meier survival curves and Cox proportional hazard analyses. RESULTS: Compared to controls, gout patients suffered more from hypertension (44.8%), diabetes (20.1%), hypercholesterolemia (13.7%), and prior cardiovascular disease (30%) (P<0.01), whereas rheumatoid arthritis patients (hypertension 28.5%; diabetes 11.7%; hypercholesterolemia 7.4%; prior cardiovascular disease 11.3%) did not (P>0.05). After adjustment, both gout and rheumatoid arthritis patients without prior cardiovascular disease were more likely to get a cardiovascular disease: hazard ratio (95% confidence interval) 1.44 (1.18 to 1.76), and 2.06 (1.34 to 3.16) respectively. CONCLUSIONS: This primary care study indicates that gout and rheumatoid arthritis are both independent risk factors for cardiovascular diseases, rheumatoid arthritis to some greater extent, whereas gout patients at first diagnosis had already an increased cardiovascular risk profile. It gives strong arguments for implementation of both rheumatic diseases in primary care guidelines on cardiovascular risk management.
27111089 Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in 2016 Sep OBJECTIVE: To assess the ability of a multi-biomarker disease activity (MBDA) test (Vectra DA) to reflect clinical measures of disease activity in patients enrolled in the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial. METHODS: In the AMPLE trial, patients with active rheumatoid arthritis (RA) who were naive to biologic agents and had an inadequate response to methotrexate were randomized (1:1) to receive subcutaneous abatacept (125 mg every week) or subcutaneous adalimumab (40 mg every 2 weeks), with background methotrexate, for 2 years. The MBDA score was determined using serum samples collected at baseline, month 3, and years 1 and 2. The adjusted mean change from baseline in the MBDA score was compared between the abatacept and adalimumab treatment groups. Cross-tabulation was used to compare the MBDA score with the following clinical measures of disease activity: Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and Routine Assessment of Patient Index Data 3 (RAPID-3). RESULTS: In total, 318 patients were randomized to receive abatacept, and 328 were randomized to receive adalimumab; MBDA data were available for 259 and 265 patients, respectively. No association between the MBDA score and disease activity defined by the CDAI, SDAI, DAS28-CRP, or RAPID-3 in the abatacept and adalimumab treatment groups was observed. CONCLUSION: The MBDA score did not reflect clinical disease activity in patients enrolled in AMPLE and should not be used to guide decision-making in the management of RA, particularly for patients who receive abatacept or adalimumab as the first biologic agent.
27379996 Interleukin-35 (IL-35) inhibits proliferation and promotes apoptosis of fibroblast-like sy 2016 Sep Rheumatoid arthritis (RA) is an inflammatory disorder of the joints that affects 0.5-1 % of adults. Excessive growth of the fibroblast-like synoviocytes (FLS) promotes hyperplasia of synovial tissues and causes its invasion into the bone and cartilage, which eventually causes deformity and dysfunction of affected joints. Interleukin 35 (IL-35) was shown to suppress the inflammatory responses to collagen-induced arthritis (CIA) via upregulation of T regulatory cells and suppression of T helper type 17 cells in a mouse model. To study the effects of IL-35 on the proliferation and apoptosis frequency of cultured FLS isolated from mice with CIA as well as to examine the effects of IL-35 on CIA in vivo. Thirty DBA/1 J mice, which are used as an animal model for RA, were divided randomly (ten mice per group) to a CIA group (collagen treatment), a CIA + IL-35 group (collagen and IL-35 treatments), and a control group (no treatment). Starting on the 24th day after collagen administration, IL-35 was injected intraperitoneally into mice of the CIA + IL-35 group once per day for 10 days. An arthritis index was calculated, and pathological analysis of synovial tissue was performed. FLS isolated from CIA mice were treated with various concentrations of IL-35 (12.5-100 ng/ml). The MTT assay was used to examine FLS proliferation, and apoptosis frequency of FLS was detected by flow cytometry. On day 24, the CIA mice began to exhibit arthritis symptoms, and the symptoms rapidly progressed with time. Treatment with IL-35 significantly alleviated arthritis symptoms and reduced the synovial tissue inflammation. In addition, IL-35 treatment inhibited proliferation and promoted apoptosis in cultured FLS from CIA mice in a dose-dependent manner. IL-35 could ameliorate the symptoms of arthritis in the CIA mouse model in vivo and inhibited FLS proliferation while promoting FLS apoptosis in vitro, thereby exhibited the potential in inhibiting the progression of RA.
26608853 [Anti-RANKL antibody for the treatment of bone and cartilage destruction in rheumatoid art 2015 Dec Rheumatoid arthritis (RA) is characterized by chronic synovitis and RANKL-dependent osteoclastogenesis leading to bone damage, which causes severe physical disability. Focal and systemic bone and cartilage destruction including secondary osteoporosis contributes to the morbidity associated with RA. The biologics targeting TNF and IL-6 has revolutionized the treatment of RA, producing significant improvements in clinical and structural outcomes. Furthermore, an anti-RANKL antibody denosumab possesses a potential to inhibit joint destruction as well as systemic osteoporosis. Targeting RANKL therapy will most likely enlarge the possibilities of osteoporosis treatment and improve the prognosis in RA patients.
25637666 Association of rs2075876 polymorphism of AIRE gene with rheumatoid arthritis risk. 2015 Apr BACKGROUND: Autoimmune regulator (AIRE), a protein encoded by AIRE gene, is a transcriptional factor primarily expressed in medullary thymic epithelial cells (mTECs). It has pivotal role in regulation of human immunology. The mutations of AIRE gene or protein level changes would alter the status of body immunity and therefore onset of diseases. Therefore we aimed at investigating the association of AIRE gene with the risk of rheumatoid arthritis (RA). METHODS: We genotyped 9 SNPs of AIRE gene of recruited 691 patients of rheumatoid arthritis and 800 healthy people in Chinese Han population. RESULTS: Our results indicated that a variant rs2075876 with minor allele A increased the risk of rheumatoid arthritis (pa=0.008, OR=1.991, 95%CI 1.214-2.919). Other two SNPs rs933150 and rs760426 were borderline-associated with rheumatoid arthritis risk (pa=0.055; pa=0.074, respectively). Furthermore, in correlation analysis of SNPs in AIRE gene with clinical characteristics of rheumatoid arthritis, we found the SNP rs2075876 had significant correlation with CRP concentration (pa=0.020). CONCLUSION: We might provide a new inside look into the AIRE gene variants in development and progression of rheumatoid arthritis.
27370881 ACR/EULAR Definitions of Remission Are Associated with Lower Residual Inflammatory Activit 2016 Sep OBJECTIVE: To determine the level of residual inflammation [synovitis, bone marrow edema (BME), tenosynovitis, and total inflammation] quantified by hand magnetic resonance imaging (h-MRI) in patients with rheumatoid arthritis (RA) in remission according to 3 different definitions of clinical remission, and to compare these remission definitions. METHODS: A cross-sectional study. To assess the level of residual MRI inflammation in remission, cutoff levels associated to remission and median scores of MRI residual inflammatory lesions were calculated. Data from an MRI register of patients with RA who have various levels of disease activity were used. These were used for the analyses: synovitis, BME according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, tenosynovitis, total inflammation, and disease activity composite measures recorded at the time of MRI. Receiver-operating characteristic analysis was used to identify the best cutoffs associated with remission for each inflammatory lesion on h-MRI. Median values of each inflammatory lesion for each definition of remission were also calculated. RESULTS: A total of 388 h-MRI sets of patients with RA with different levels of disease activity, 130 in remission, were included. Cutoff values associated with remission according to the Simplified Disease Activity Index (SDAI) ≤ 3.3 and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definitions for BME and tenosynovitis (1 and 3, respectively) were lower than BME and tenosynovitis (2 and 5, respectively) for the Disease Activity Score on 28 joints (DAS28) ≤ 2.6. Median scores for synovitis, BME, and total inflammation were also lower for the SDAI and Boolean ACR/EULAR remission criteria compared with DAS28. CONCLUSION: Patients with RA in remission according to the SDAI and Boolean ACR/EULAR definitions showed lower levels of MRI-detected residual inflammation compared with DAS28.