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ID PMID Title PublicationDate abstract
27585710 Cyr61 participates in the pathogenesis of rheumatoid arthritis via promoting MMP-3 express 2017 May OBJECTIVES: The aim of this study was to investigate the effect and potential mechanism of Cysteine-rich 61 (Cyr61) on stimulating MMP-3 expression by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: Primarily cultured RA FLS were treated with exogenous Cyr61 protein or Cyr61-siRNA, then, MMP-3 expression was analyzed by real-time PCR, western blotting and ELISA. Signal transduction pathways in Cyr61-induced MMP-3 production were examined by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay. Mice with collagen-induced arthritis (CIA) were treated with anti-Cyr61 monoclonal antibodies (mAb), or IgG1 as control and MMP-3 in the joint was detected by IHC, real-time PCR and western blotting. RESULTS: High expressed MMP-3 and Cyr61 were positively correlated in RA ST; Cyr61 stimulated MMP-3 production in FLS of RA patients in an IL-1β and TNF-α independent manner. Cyr61 induced MMP-3 could further enhance the invasive ability of RA FLS. Mechanistically, we found that Cyr61 promoted MMP-3 production via the P38, JNK-dependent AP-1 signaling pathway. Blockage of Cyr61 function with monoclonal antibody could decrease MMP-3 expression in the joints of CIA mice. CONCLUSION: This study provides new evidence that Cyr61 participates in RA pathogenesis not only as a pro-inflammatory factor but also plays a key role in bone erosion via promoting MMP-3 expression. We suggest that targeting of Cyr61 may represent a potential strategy in RA treatment.
26853758 Sports after shoulder arthroplasty: a comparative analysis of hemiarthroplasty and reverse 2016 Jun BACKGROUND: Traditionally, fewer postoperative sport restrictions are imposed on hemiarthroplasty (HHA) patients on than reverse total shoulder arthroplasty (RTSA) patients. However, functional outcomes have been shown to be superior in RTSA. No direct comparison of RTSA vs HHA has been done on rates of return to sports in patients with glenohumeral arthritis and rotator cuff dysfunction, proximal humeral fractures, or rheumatoid arthritis. METHODS: This is a retrospective review of consecutive RTSA and HHA patients collected from our institution's shoulder arthroplasty registry. All patients playing sports preoperatively with minimum 1-year follow-up were included. Final follow-up included an additional patient-reported questionnaire with questions regarding physical fitness and sport activities. RESULTS: The study included 102 RTSA and 71 HHA patients. Average age at surgery was 72.3 years for RTSA compared with 65.6 years for HHA (P < .001). Patients undergoing RTSA had improved visual analog scale scores compared with HHA (-5.6 vs -4.2, P = .007), returned to sports after RTSA at a significantly higher rate (85.9% vs 66.7%, P = .02), and were more likely to be satisfied with their ability to play sports (P = .013). HHA patients were also more likely to have postoperative complaints than RTSA patients (63% vs 29%, P < .0001). No sports-related complications occurred. Female sex, age <70 years, surgery on the dominant extremity, and a preoperative diagnosis of arthritis with rotator cuff dysfunction predicted a higher likelihood of return to sports for patients undergoing RTSA compared with HHA. CONCLUSIONS: Despite traditional sport restrictions placed on RTSA, patients undergoing RTSA can return to sports at rates higher than those undergoing HHA, with fewer postoperative complaints.
25748956 Methotrexate-related primary hepatic lymphoma in a patient with rheumatoid arthritis. 2015 A 56-year-old woman with rheumatoid arthritis treated with methotrexate (MTX) was admitted to our hospital due to multiple liver tumors. Contrast-enhanced computed tomography (CT) revealed multiple hypovascular masses, and 18F-fluorodeoxyglucose positron emission tomography CT showed diffuse abnormal accumulation in the liver only. We therefore made a diagnosis of MTX-related primary hepatic lymphoma (MTX-PHL) exhibiting features of diffuse large B-cell lymphoma. Although MTX has been reported to increase the risk of lymphoproliferative disorders, MTX-PHL has not been reported previously. The present case is the first case in which MTX appears to have been involved in the development of PHL.
26335941 Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis. 2015 Sep 3 INTRODUCTION: Increasing evidence indicates that features suggestive of neuropathic pain may also be present in patients with common rheumatic conditions. The objective of this study was to examine neuropathic-like pain symptoms and associated factors in patients with rheumatoid arthritis. METHODS: We used the painDETECT screening tool to identify possible or likely neuropathic pain in 159 outpatients with rheumatoid arthritis. Patients additionally completed other self-reported measures, while clinical measures were assessed to calculate the 28-joint Disease Activity Score. Univariate analyses and multivariable logistic regression were used to identify factors associated with neuropathic pain features. RESULTS: According to the painDETECT, 27 patients (17.0 %) were classified as having likely neuropathic pain and 34 patients (21.4 %) as having possible neuropathic pain. Besides reporting more severe pain, patients with likely or possible neuropathic pain were more likely to meet the diagnostic criteria for fibromyalgia, to use analgesics, and to have more tender joints and a worse physical and mental health status as measured by the 36-item Short-Form health survey. In multivariable analysis, physical (P < 0.001) and mental health status (P = 0.006) remained significantly associated with neuropathic pain features, even after controlling for pain severity. CONCLUSIONS: These findings suggest that a sizeable proportion of patients with relatively well-controlled rheumatoid arthritis report symptoms suggestive of neuropathic pain. Neuropathic-like pain symptoms are independently associated with worse self-reported physical and mental health.
26861097 [Immunodeficiency-associated Burkitt lymphoma developed in a patient receiving a long-term 2016 Jan An increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of immunodeficiency-associated LPDs. We herein present a RA patient, who developed Burkitt lymphoma during MTX treatment. The patient was a 61-year-old Japanese female with a 10-year history of weekly MTX therapy for RA. She presented with a one-month history of submandibular lymph node swelling and fever. Remarkable increases in serum lactate dehydrogenase and blood EBV DNA were observed. Serology for HIV was negative. Biopsy specimens demonstrated diffuse proliferation of medium-sized lymphoid cells. The cells were positive for CD10, CD20 and BCL6, and negative for BCL2, MUM1, terminal deoxynucleotidyl transferase and CD34. The MIB-1 index was almost 100%. EBV in the tumor cells was identified by using EBV-encoded RNA in situ hybridization. A chromosomal translocation t(8;14) was found and further confirmed by fluorescence in situ hybridization. Her condition improved following discontinuation of MTX and initiation of prednisolone. After three cycles of a dose-reduced CHOP-like regimen, chemotherapy was discontinued due to severe complications. However, there has been no sign of recurrence for six years to date without additional intensive chemotherapy.
26879718 [Clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid art 2016 Jan 19 OBJECTIVE: The research aimed to evaluate the level and clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid arthritis (RA). METHODS: Totally 82 untreated RA female patients (RA group) and 32 healthy females (control group) were enrolled.According to the disease activity score in 28 joints (DAS28), patients in RA group were divided into remission stage group (<2.6 scores, 32 cases) and active stage group (≥2.6 scores, 50 cases). The correlations of 25-hydroxyvitamin D (25-(OH)-D) level with related indicators were analyzed. RESULTS: (1)The levels of serum 25-(OH)-D in female RA active stage group were significantly lower than those in control group [(12.5±6.3) μg/L vs (26.6±5.3) μg/L ] (P<0.01). The levels of serum 25-(OH)-D in female RA remission stage group were significantly lower than those in control group [(14.2±7.2) μg/L vs (26.6±5.3) μg/L] (P<0.01). (2)Serum 25-(OH)-D levels were inversely associated with C reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28 score (r=-0.575, r=-0.528, r=-0.354, P<0.05) in female RA active stage group, but not in female RA remission stage group (P>0.05). (3)In active stage group, the 25-(OH)-D levels of premenopausal RA patients were negatively correlated with CRP, ESR, DAS28 (r=-0.707, r=-0.625, r=-0.487, P<0.05), but not in postmenopausal RA patients (P>0.05). CONCLUSIONS: The 25-(OH)-D levels in serum are reduced in female patients with RA.Serum 25-(OH)-D level can be a marker to monitor the disease activity in RA premenopausal female patients.
27784891 Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers 2016 Dec The treatment and outcomes of patients with rheumatoid arthritis (RA) have been transformed over the past two decades. Low disease activity and remission are now frequently achieved, and this success is largely the result of the evolution of treatment paradigms and the introduction of new therapeutic agents. Despite the rapid pace of change, the most commonly used drug in RA remains methotrexate, which is considered the anchor drug for this condition. In this Review, we describe the known pharmacokinetic properties and putative mechanisms of action of methotrexate. Consideration of the pharmacodynamic perspective could inform the development of biomarkers of responsiveness to methotrexate, enabling therapy to be targeted to specific groups of patients. Such biomarkers could revolutionize the management of RA.
27231112 Functional Components from Nature-Derived Drugs for the Treatment of Rheumatoid Arthritis. 2016 Rheumatoid arthritis (RA) is a chronic systemic disorder characterized by persistent synovitis and systemic inflammation. Currently, the widely used drugs for the treatment of RA are disease-modifying antirheumatic drugs, biological agents and glucocorticoids. But their clinical use has been limited because of their adverse effects with a high frequency and high cost of treatment. It is essential to find novel candidate agents. Traditional Chinese medicine (TCM) has been used for RA treatment for a long period of time. In recent years, significant amounts of studies have shown that some TCMs and their active ingredients have obvious therapeutic effects on RA. In this review, the compounds in TCMs that have an effect in clinic or animal experiments of RA are critically reviewed and summarized. Moreover, the relationship between chemical structures of the compound and their activities is analyzed. The relevant researches are described from the aspects of source, methods, result, and related mechanism analysis. The existing studies show that most effective compounds in TCM for RA treatment belong to alkaloids, flavonoids, terpenoids, phenols and quinines. It is hoped that the data summarized in this review will be beneficial to the screening of new nature-derived antirheumatic drugs.
27213695 Magnetic Resonance Imaging-Detected Features of Inflammation and Erosions in Symptom-Free 2016 Nov OBJECTIVE: The use of magnetic resonance imaging (MRI)-detected inflammation and joint damage in the diagnosis of rheumatoid arthritis is recommended by a European League Against Rheumatism imaging task force. This recommendation is based on the sensitivity of MRI and not on specificity. Knowledge of the prevalence of MRI-detected features in symptom-free persons, however, is pivotal when considering MRI for diagnostic purposes. METHODS: From November 2013 to December 2014, 196 symptom-free persons of different ages were recruited from the general population. Inclusion criteria were no history of inflammatory arthritis, no joint symptoms during the previous month, and no clinically detectable arthritis on physical examination. Contrast-enhanced MRIs of the dominant metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints were obtained using a 1.5T scanner and scored by 2 readers for synovitis, bone marrow edema, tenosynovitis, and erosions. For analyses at the joint level, MRI-detected inflammation was considered present if both readers scored the image as positive. RESULTS: Of 193 persons scanned (ages 19-89 years), only 28% had no single inflammatory feature and 22% had no erosions. Primarily low-grade features were observed. All MRI features were positively correlated with age (P < 0.001). Preferential locations for synovitis were MCP2, MCP3, the wrists, and MTP1. Bone marrow edema was frequently present in MCP3, the scaphoid, and MTP1. Tenosynovitis was infrequent, except for in the extensor carpi ulnaris. Preferential locations for erosions were MCP2, MCP3, MCP5, the distal ulna, MTP1, and MTP5. Tables with age-, location-, and inflammation type-dependent frequencies were constructed. Simultaneous colocalized presence of synovitis, bone marrow edema, tenosynovitis, or erosions occurred. CONCLUSION: MRI-detected inflammation and erosions are prevalent in symptom-free persons from the general population, especially at older ages and at preferential locations.
26610397 Increased inflammation in rheumatoid arthritis patients living where farm soils contain hi 2016 Nov BACKGROUND/PURPOSE: Heavy metal pollution in farm soils is a problem in some parts of Taiwan. Copper can be a factor associated with increased disease activities of rheumatoid arthritis (RA). Thus, the aim of this study was to investigate whether copper pollution in farm soils is associated with worsened RA. METHODS: Clinical parameters from 122 RA patients were collected from a medical center in central Taiwan. Levels of heavy metals in the blood were measured using inductively coupled plasma mass spectrometry. Levels of copper in farm soils were retrieved from a national survey. These data were analyzed to find the factors related to RA disease activities. RESULTS: RA patients living where farm soils contained high levels of copper had increased white blood cell counts, erythrocyte sedimentation rate, and disease activity score 28, compared with patients living where copper levels were low. Among the nine types of heavy metal measured in the study, blood levels of copper and nickel correlated with erythrocyte sedimentation rate. CONCLUSION: Our cross-sectional data suggest a correlation between RA disease activity and the level of copper at township farm soils samples. Further longitudinal studies using more rigorous methodologies are warranted to examine whether this correlation is causal.
24326008 Key findings towards optimising adalimumab treatment: the concentration-effect curve. 2015 Mar OBJECTIVE: To determine a concentration-effect curve of adalimumab in rheumatoid arthritis (RA) patients taking into account the effect of methotrexate (MTX) on concentration and effect and to identify a therapeutic range for adalimumab concentrations. METHODS: In a prospective observational cohort study, 221 consecutive patients with RA were treated with 40 mg adalimumab subcutaneously every other week. The relationship between adalimumab trough level and clinical efficacy after 28 weeks of follow-up was determined in a concentration-effect curve. A receiver-operator characteristics (ROC) curve established a therapeutic cut-off concentration. The effect of MTX on adalimumab trough levels was shown by dividing patients that are and are not concomitantly using MTX in the concentration-effect curve and a concentration table. RESULTS: Clinical efficacy improved with increasing adalimumab concentration and reached a maximum (mean disease activity score in 28 joints improvement of 2) with levels between 5-8 μg/mL. Levels exceeding 8 μg/mL were illustrated to have no additional beneficial effect on disease activity. The ROC curve showed an area under the curve of 0.695 (95% CI 0.626 to 0.764) for European League Against Rheumatism response and adalimumab levels: good responders versus non-responders and moderate responders. A cut-off of 5 μg/mL had a sensitivity of 91% and a specificity of 43%. Adalimumab levels are influenced by concomitant MTX use: patients on adalimumab monotherapy had a median adalimumab level of 4.1 μg/mL (IQR 1.3-7.7), whereas patients concomitantly taking MTX had a median level of 7.4 μg/mL (IQR 5.3-10.6, p<0.001). CONCLUSIONS: Adalimumab trough levels in a range of 5-8 μg/mL are sufficient to reach adequate clinical response. These levels are influenced substantially by concomitant MTX use.
26653844 Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthrit 2015 Dec 10 INTRODUCTION: Despite the broad spectrum of antirheumatic drugs, RA is still not well controlled in up to 30-50 % of patients. Inhibition of JAK kinases by means of the pan-JAK inhibitor tofacitinib has demonstrated to be effective even in difficult-to-treat patients. Here, we discuss whether the efficacy of JAK inhibition can be improved by simultaneously inhibiting SYK kinase, since both kinases mediate complementary and non-redundant pathways in RA. METHODS: Efficacy of dual JAK + SYK inhibition with selective small molecule inhibitors was evaluated in chronic G6PI-induced arthritis, a non-self-remitting and destructive arthritis model in mice. Clinical and histopathological scores, as well as cytokine and anti-G6PI antibody production were assessed in both preventive and curative protocols. Potential immunotoxicity was also evaluated in G6PI-induced arthritis and in a 28-day TDAR model, by analysing the effects of JAK + SYK inhibition on hematological parameters, lymphoid organs, leukocyte subsets and cell function. RESULTS: Simultaneous JAK + SYK inhibition completely prevented mice from developing arthritis. This therapeutic strategy was also very effective in ameliorating already established arthritis. Dual kinase inhibition immediately resulted in greatly decreased clinical and histopathological scores and led to disease remission in over 70 % of the animals. In contrast, single JAK inhibition and anti-TNF therapy (etanercept) were able to stop disease progression but not to revert it. Dual kinase inhibition decreased Treg and NK cell counts to the same extent as single JAK inhibition but overall cytotoxicity remained intact. Interestingly, treatment discontinuation rapidly reversed such immune cell reduction without compromising clinical efficacy, suggesting long-lasting curative effects. Dual kinase inhibition reduced the Th1/Th17 cytokine cascade and the differentiation and function of joint cells, in particular osteoclasts and fibroblast-like synoviocytes. CONCLUSIONS: Concurrent JAK + SYK inhibition resulted in higher efficacy than single kinase inhibition and TNF blockade in a chronic and severe arthritis model. Thus, blockade of multiple immune signals with dual JAK + SYK inhibition represents a reasonable therapeutic strategy for RA, in particular in patients with inadequate responses to current treatments. Our data supports the multiplicity of events underlying this heterogeneous and complex disease.
27475664 Advanced oxidation protein products induce catabolic effect through oxidant-dependent acti 2016 Oct Advanced oxidation protein products (AOPPs) have been shown to participate in the progression of rheumatoid arthritis (RA). However, the effect of AOPPs accumulation on catabolic effect in human chondrocyte and the underlying mechanism(s) remain unclear. The present study demonstrated that AOPPs inhibited cell viability and glycosaminoglycan (GAG) production in human chondrocyte. Exposure of chondrocyte to AOPPs significantly increased the production of catabolic factors, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMPs)-3 and MMP-13. AOPPs stimulation induced ROS generation and NF-κ B p65 phosphorylation, which could be inhibited by soluble receptor for advanced glycan end products (sRAGE), NADPH oxidase inhibitor (apocynin), ROS scavenger (N-acetyl-cysteine, NAC). Furthermore, NF-κ B inhibitor Bay11-7082 significantly reversed the AOPPs-induced expression of catabolic factors and phosphorylation of NF-κ B p65. Targeting AOPPs-triggered catabolic effect might be as a promising option for patients with RA.
26822072 Effectiveness and safety of abatacept in elderly patients with rheumatoid arthritis enroll 2016 May OBJECTIVE: To study the effect of age on the risk-benefit balance of abatacept in RA. METHODS: Data from the French orencia and RA registry, including a 2-year follow-up, were used to compare the effectiveness and safety of abatacept according to age. RESULTS: Among the 1017 patients, 103 were very elderly (⩾75 years), 215 elderly (65-74), 406 intermediate aged (50-64) and 293 very young (<50). At baseline, elderly and very elderly patients had longer disease duration, higher CRP levels and higher disease activity. These age groups showed a lower incidence of previous anti-TNF therapy and less common concomitant use of DMARDs, but a similar use of corticosteroid therapy. After adjusting for disease duration, RF/ACPA positivity, use of DMARDs or corticosteroids and previous anti-TNF treatment, the EULAR response (good or moderate) and the remission rate were not significantly different between the four age groups. At 6 months, the very elderly had a significantly lower likelihood of a good response than the very young (odds ratio = 0.15, 95% CI: 0.03, 0.68). The decrease in DAS28-ESR over the 24-month follow-up period did not differ by age. Increasing age was associated with a higher rate of discontinuation for adverse events, especially severe infections (per 100 patient-years: 1.73 in very young, 4.65 in intermediates, 5.90 in elderly, 10.38 in very elderly; P < 0.001). CONCLUSION: The effectiveness of abatacept is not affected by age, but the increased rate of side effects, especially infections, in the elderly must be taken into account.
27386793 A global test for gene-gene interactions based on random matrix theory. 2016 Dec Statistical interactions between markers of genetic variation, or gene-gene interactions, are believed to play an important role in the etiology of many multifactorial diseases and other complex phenotypes. Unfortunately, detecting gene-gene interactions is extremely challenging due to the large number of potential interactions and ambiguity regarding marker coding and interaction scale. For many data sets, there is insufficient statistical power to evaluate all candidate gene-gene interactions. In these cases, a global test for gene-gene interactions may be the best option. Global tests have much greater power relative to multiple individual interaction tests and can be used on subsets of the markers as an initial filter prior to testing for specific interactions. In this paper, we describe a novel global test for gene-gene interactions, the global epistasis test (GET), that is based on results from random matrix theory. As we show via simulation studies based on previously proposed models for common diseases including rheumatoid arthritis, type 2 diabetes, and breast cancer, our proposed GET method has superior performance characteristics relative to existing global gene-gene interaction tests. A glaucoma GWAS data set is used to demonstrate the practical utility of the GET method.
26980096 Pre-operative templating in total elbow arthroplasty: not useful. 2016 May PURPOSE: Total elbow arthroplasty (TEA) is a definitive surgical procedure for treating rheumatoid arthritis and (posttraumatic) osteoarthritis of the elbow and is also useful in comminuted elbow fractures. Pre-operative digital templating may theoretically improve the surgical implantation of TEA, but reliability and predictive values of templating are unknown. The aim of this study was to determine the intra- and inter-observer reliability and the validity of pre-operative digital templating for TEA. MATERIALS AND METHODS: All pre-operative plain anterior-posterior and lateral calibrated elbow radiographs from patients who underwent TEA in our center from 2008 to June 2014 were reviewed. Two independent assessors templated implant sizes using digital overlays twice. Intra- and inter-observer reliability were evaluated with Cohen's kappa. Two experienced elbow surgeons reviewed post-operative radiographs for evaluation. The predictive value of templating was the percentage of the correctly templated sizes, with the optimal implant size as the reference standard. RESULTS: Twenty-one cases were included. Intra-observer reliability was substantial to almost perfect (κ = 0.61 and κ = 0.90) for humeral implants, moderate to substantial (κ = 0.54 and κ = 0.73) for ulnar implants. Inter-observer reliability was substantial (κ = 0.67) for humeral implants and moderate (κ = 0.60) for ulnar implants. The predictive value was 53 % for both implants. CONCLUSIONS: Pre-operative digital templating for TEA is a reliable method to plan implant sizes. However, the predictive value is low.
25530318 Cost per patient-year in response using a claims-based algorithm for the 2 years following 2015 May OBJECTIVE: To estimate cost per patient-year in response during 2 years following biologic initiation among patients with rheumatoid arthritis (RA). METHODS: Adults newly initiating biologics for RA (etanercept, abatacept, adalimumab, certolizumab, golimumab, or infliximab) between January 2009 and July 2011 were identified in the MarketScan Commercial Database. Eligible patients were continuously enrolled 6 months before (pre-index) and 24 months after (post-index) their first (index) biologic claim. Biologic effectiveness was assessed using six criteria during 2-year follow-up: treatment adherence ≥80%, no biologic dose escalation, no biologic switch, no new disease-modifying anti-rheumatic drug, no new/increased glucocorticoid dose, and limited intra-articular joint injections (≤2). After a 90-day period of non-response for a treatment failure, effectiveness or failure of subsequent treatment was assessed again for the index biologic or new biologic (after switching). Post-index RA-related medical, pharmacy, and drug administration costs were attributed to the index biologic. Cost per patient-year in response was calculated as RA-related costs divided by duration of response. RESULTS: Overall, 15.0% of patients (1229/8193) did not fail any criterion for 2 years and were effectively treated. Mean duration of response was highest for etanercept (538.3 days), followed by golimumab (537.0 days; p = 0.864), adalimumab (534.7 days; p = 0.301), certolizumab (524.0 days; p = 0.165), infliximab (480.0 days; p < 0.001), and abatacept (482.3 days; p < 0.001). Total disease-related cost per patient-year in response was lower for patients initiated on etanercept ($25,086) than for patients initiated on adalimumab ($25,960), certolizumab ($26,339), golimumab ($26,332), abatacept ($35,581), or infliximab ($36,107). LIMITATIONS: This study was limited to employer-paid commercial insurance. Database analyses cannot determine reasons for failing criteria. The algorithm was not designed and validated for 2 years of follow-up. CONCLUSIONS: An effectiveness algorithm estimated that initiating etanercept was the most effective treatment during 2 years of follow-up, with the lowest cost per patient-year in response.
25187198 Perioperative use of anti-rheumatic agents does not increase early postoperative infection 2015 Feb The aim of this study was to validate a novel technique that predicts stopping of disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents (BA) from the Veterans Affairs (VA) database and compare infection risks of rheumatoid arthritis patients who stopped versus continued DMARDs/BA perioperatively. We identified 6,024 patients on 1 DMARD or BA in the perioperative period between 1999 and 2009. Time gap between medication stop date and the next start date predicted drug stoppage (X). Time gap between surgery date and stop date predicted whether stoppage was before surgery (Y). Chart review from Houston VA was used for validation. ROC analyses were performed on chart review data to obtain X and Y cutoffs. The primary endpoints were wound infections and other infections within 30 days. ROC analyses found X ≥ 33 (AUC = 0.954) and Y ≥ -11 (AUC = 0.846). Risk of postoperative infections was not different when stopping and continuing DMARDs/BA preoperatively. Stopping BA after surgery was associated with higher odds of postoperative wound (OR 14.15, 95 % CI 1.76-113.76) and general infection (OR 9.2, 95 % CI 1.99-42.60) compared to not stopping. Stopping DMARDs after surgery was associated with increased risk of postoperative general infection (OR 1.84, 95 % CI 1.07-3.16) compared with not stopping. There was positive association between stopping DMARDs after surgery and postoperative wound infection but failed to achieve statistical significance (OR 1.67, 95 % CI 0.96-2.91). There was no significant difference in postoperative infection risk when stopping or continuing DMARD/BA. Our new validated method can be utilized in the VA and other databases to predict drug stoppage.
26290061 Ten years of change in clinical disease status and treatment in rheumatoid arthritis: resu 2015 Aug 20 INTRODUCTION: In the new millennium, clinical outcomes in patients with rheumatoid arthritis (RA) have improved. Despite a large number of register data, there is a lack of data reflecting the entire outpatient RA population, and in particular long-term data. The main aim of this study was to explore changes in clinical disease status and treatment in an RA outpatient clinic population monitored with recommended outcome measures over a 10-year period. METHODS: Standard data collected included demographic data, erythrocyte sedimentation rate, C-reactive protein, clinical measures of disease activity (Disease Activity Score in 28 joint counts [DAS28], Clinical Disease Activity Index [CDAI], Simplified Disease Activity Index [SDAI] and global assessments) and patient-reported outcomes (measures of physical function, joint pain, fatigue, patient global assessment and morning stiffness). Treatment with disease-modifying antirheumatic drugs (DMARDs) was also recorded, as well as rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status. RESULTS: In the RA population, the mean age was approximately 64 years and disease duration was 10-12 years. About 70 % were females; approximately 20 % were current smokers; and 65-70 % were positive for RF and ACPA. During follow-up, disease activity improved significantly. When we applied the DAS28, CDAI, SDAI and Boolean criteria for remission, the proportions of patients in remission increased from 21.3 %, 8.1 %, 5.8 % and 3.8 %, respectively, in 2004 to 55.5 %, 31.7 %, 31.8 % and 17.7 %, respectively, in 2013. The proportions of patients with DAS28, CDAI and SDAI low disease activity status were 16.0 %, 34.0 %, and 34.9 %, respectively, in 2004 and 17.8 %, 50.4 % and 50.8 %, respectively, in 2013. A significant improvement in patient-reported outcome was seen only for the full 10-years, but not for the last 4 years, of the study period. The proportion of patients taking synthetic (about 60 %) and biologic (approximately 30 %) DMARDs was stable over the last 4 years of the study period, with no significant change observed, whereas the proportion of patients being treated with prednisolone was reduced significantly from 61 % in 2010 to 54 % in 2013. CONCLUSIONS: The encouraging data we present suggest that the vast majority of patients with RA monitored in outpatient clinics in the new millennium can expect to achieve a status of clinical remission or low disease activity.
25990747 Associations of antibodies against citrullinated peptides with human leukocyte antigen-sha 2015 May 20 INTRODUCTION: It has previously been shown that an increased number of antibodies against citrullinated peptides/proteins (ACPA) predate the onset of rheumatoid arthritis (RA). Over time antibody positivity expands, involving more specific responses when approaching the onset of symptoms. We investigated the impact of human leukocyte antigen-shared epitope (HLA-SE) alleles and smoking on the development of ACPA, as well as in combination with ACPA during the state of quiescent autoimmunity (before the onset of symptoms), on the development of RA. METHODS: Blood samples donated to the Medical Biobank of Northern Sweden from individuals prior to the onset of symptoms of RA (n=370) and after onset (n=203) and from population-based controls (n=585) were used. Antibodies against 10 citrullinated peptides, fibrinogen (Fibα561-583, α580-600, ß62-81a, ß62-81b, ß36-52), vimentin (Vim2-17, 60-75), filaggrin (CCP-1/Fil307-324), α-enolase (CEP-1/Eno5-21), collagen type II (citC1359-369), and anti-cyclic citrullinated peptide (CCP)2 antibodies were analysed. RESULTS: HLA-SE-positive individuals were more frequently positive for ACPA compared with HLA-SE-negative individuals prior to the onset of symptoms of RA, particularly for antibodies against CEP-1 and Fibß62-81a (72). Smoking was associated with antibodies against Vim2-17 and citC1359-369. HLA-SE and smoking showed increasing association to the presence of the antibodies closer to disease onset. The highest odds ratio (OR) for development of RA was for the combination of HLA-SE alleles and ACPA positivity, especially for antibodies against Fibß62-81b, CCP-1/Fil307-324, and Fibβ36-52. A gene-environment additive interaction between smoking and HLA-SE alleles for the risk of disease development was found, with the highest OR for individuals positive for antibodies against Fibβ36-52, CEP-1, and Fibα580-600. CONCLUSIONS: The relationships between antibodies against the different ACPA specificities, HLA-SE, and smoking showed a variable pattern in individuals prior to the onset of RA. The combination of smoking and HLA-SE alleles was significantly associated with the development of some of the antibody specificities closer to onset of symptoms, and these associations remained significant at diagnosis. An additive gene-environment interaction was found for several of the antibodies for the development of RA.