Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30244471 Design an Intervention Study. 2018 Randomized controlled trials are commonly designed to compare the effectiveness of treatments in rheumatoid arthritis (RA). In a clinical trial (intervention study), researchers apply interventions or preventive services to patients and examine outcomes. Clinical trial design consists of the following categories: choice of intervention, selection of patients, informed consent, baseline measurement, bank specimens, randomized allocation and blinding, and outcome measurements. Here, we discuss the design of clinical trials for RA.
30053199 Predictors of sustained remission in patients with early rheumatoid arthritis treated acco 2018 Nov 1 OBJECTIVES: To study prognostic factors for achievement of sustained remission in early RA patients receiving semi-personalized tight controlled treatment, and to assess the consistency of potential predictors across definitions of sustained remission. METHODS: DMARD-naïve early RA patients with symptom duration <2 years were treated according to a pre-defined algorithm within the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen trial. The algorithm allowed treatment adjustments based on established risk factors for a worse outcome. Multivariate logistic regression was used to examine baseline predictors of achieving sustained DAS remission at 16-24 months, and to assess predictors of secondary remission outcomes (all sustained 16-24 months): ACR/EULAR Boolean, Simplified Disease Activity Index (SDAI), no swollen joints and a composite outcome of DAS remission, no swollen joints and no radiographic progression. RESULTS: Of 222 patients, 118 (53%) reached sustained DAS remission, while 53 (24%) reached sustained ACR/EULAR Boolean and 73 (33%) sustained SDAI remission. More joint tenderness, assessed by Ritchie Articular Index, was a negative predictor of reaching sustained DAS remission (odds ratio (OR) = 0.90/U, 95% CI: 0.86, 0.94), sustained ACR/EULAR Boolean remission (OR = 0.92, 95% CI: 0.86, 0.98), sustained SDAI remission (OR = 0.94, 95% CI: 0.90, 1.00) as well as the two alternative definitions of sustained remission. Short symptom duration at baseline predicted sustained Boolean and SDAI remission. Other identified predictors were inconsistent across outcomes. CONCLUSION: A higher tender joint score at baseline consistently reduced the chance of reaching sustained remission across all definitions. Our results support sustained remission as an achievable goal in early RA, especially when initiating DMARDs within 3 months symptom duration. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01205854.
29247126 Preference phenotypes to facilitate shared decision-making in rheumatoid arthritis. 2018 May OBJECTIVE: Implementing treat-to-target (TTT) strategies requires that patients with rheumatoid arthritis (RA) and their rheumatologists decide on how best to escalate care when indicated. The objective of this study was to develop preference phenotypes to facilitate shared decision-making at the point of care for patients failing methotrexate monotherapy. METHODS: We developed a conjoint analysis survey to measure the preferences of patient with RA for triple therapy, biologics and Janus kinase (JAK) inhibitors. The survey included seven attributes: administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information and cost. Each choice set (n=12) included three hypothetical profiles. Preference phenotypes were identified by applying latent class analysis to the conjoint data. RESULTS: 1273 participants completed the survey. A five-group solution was chosen based on progressively lower values of the Akaike and Bayesian information criteria. Members of the largest group (group 3: 38.4%) were most strongly impacted by the cost of the medication. The next largest group (group 1: 25.8%) was most strongly influenced by the risk of bothersome side effects. Members of group 2 (11.2%) were also risk averse, but were most concerned with the risk of very rare side effects. Group 4 (6.6%) strongly preferred oral over parenteral medications. Members of group 5 (18.0%) were most strongly and equally influenced by onset of action and the risk of serious infections. CONCLUSIONS: Treatment preferences of patients with RA can be measured and represented by distinct phenotypes. Our results underscore the variability in patients' values and the importance of using a shared decision-making approach to implement TTT.
30256536 RNA-seq analysis reveals different gene ontologies and pathways in rheumatoid arthritis an 2018 Sep AIMS: To understand the pathogenesis of cartilage damage in Kashin-Beck disease (KBD) and rheumatoid arthritis (RA) which similar clinical symptoms. METHODS: RNA sequencing (RAN-seq) analysis was used to reveal the different pathogeneses between KBD and RA. The messenger RNA expression profiles of articular cartilage isolated from KBD patients (n = 3) and RA patients (n = 3) were compared using RNA-seq analysis. Differentially expressed genes (DEGs) were determined using the Benjamini-Hochberg approach. The Database for Annotation, Visualization and Integrated Discovery (DAVID 6.7) was employed to assess functional categories and Gene Ontology (GO). The Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology Based Annotation System (KOBAS 2.0) was used to identify significantly enriched KEGG pathways. RESULTS: In the individually sequenced dataset, we identified 1568 significant DEGs in KBD compared to RA (232 up-regulated genes and 1336 down-regulated genes). GO function analysis identified nine significant biological processes (BPs), eight molecular functions (MFs), and five cell components (CCs) in KBD, and also the top ten ranked significant BPs, MFs and CCs were found in RA. The KEGG pathway enrichment analysis identified biosynthesis of amino acids involved in KBD. The chemokine signaling pathway, nuclear factor-kappa B signaling pathway, B cell receptor signaling pathway, leukocyte transendothelial migration, and osteoclast differentiation were involved in RA. CONCLUSIONS: RNA-seq revealed that proteoglycan-mediated metabolic disorders contributed to the onset of KBD, whereas immune dysregulation was apparently involved in the pathogenesis of RA.
29624881 Study on association of human leukocyte antigen-DRB1 alleles amongst Bangladeshi patients 2018 Aug INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic and autoimmune disease affecting 0.5-1% of the world population. Genetic and environmental factors are already established as being involved in the development of RA. Different human leukocyte antigen (HLA)-DRB1 alleles have major pathogenic effects to the development of RA. OBJECTIVE: To determine the HLA-DRB1 allelic frequency of RA in one Bangladeshi tertiary care center. METHODS: This case-control study was conducted at the Microbiology and Rheumatology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU). Fifty-two patients diagnosed as having RA and 52 healthy controls were enrolled. Buccal swabs were collected from all subjects and HLA-DRB1 typing was carried out with polymerase chain reaction with sequence-specific primers (PCR-SSP) of low resolution. Blood was also collected for auto-antibodies (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) detection from all subjects. RF was detected by nephelometry and anti-CCP was detected by using the enzyme-linked immunosorbent assay method. Statistical associations of HLA antigen between the groups were determined by chi-square test. RESULTS: In RA patients DR*04 and DR*10 were found at the DRB1 locus at higher frequencies (20.5%, P = 0.0035 and 18.3%, P = 0.0045, respectively). However, the frequency of DR*15 was significantly lower (P = 0.005) in RA cases (18.3%) than the control group (35.6%). The frequencies of autoantibodies (anti-CCP and RF) were compared between approximate shared epitope (SE) positive and SE negative patients, and no significant association was found. CONCLUSIONS: In this study DRB1*04 and DRB1*10 alleles were significantly associated with RA patients while DRB1*15 was found more in the control group.
29458278 Secukinumab after anti-tumour necrosis factor-α therapy: a phase III study in active rheu 2018 Jul OBJECTIVE: To assess the efficacy and safety of secukinumab in patients with rheumatoid arthritis (RA) who failed to respond to tumour necrosis factor- α (TNF-α) inhibitors. METHOD: This phase III double-blind, double-dummy, placebo-controlled study (NCT01770379) randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks. American College of Rheumatology (ACR) 20 response at week 24 was the primary endpoint. Secondary outcomes included the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP), Health Assessment Questionnaire Disability Index (HAQ-DI), and ACR50 at week 24. Long-term treatment was planned for 5 years. RESULTS: ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo. None of the secondary endpoints was met for either secukinumab dose. Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups. No new or unexpected adverse events were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies. CONCLUSIONS: Given that other second-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings may suggest that interleukin-17A inhibition with secukinumab does not provide additional benefit to these patients. This study further confirms the well-characterized safety profile of secukinumab.
29879317 Clinical effectiveness of influenza vaccination in patients with rheumatoid arthritis. 2018 Jun OBJECTIVE: To determine the clinical effectiveness of influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: The present study was conducted by using the Taiwan National Health Insurance Research Database. In this retrospective nationwide study, we included 3748 RA patients who received influenza vaccinations in 2008, 2009 and 2010, and 3748 matched RA patients who did not receive influenza vaccinations. We followed the patients from 4 weeks after influenza vaccination to the end of the influenza season in each year. After adjustment for potential confounding factors, including disease-modifying anti-rheumatic drugs, we used the Cox proportional hazards regression model to analyze the clinical effectiveness of influenza vaccination. RESULTS: The influenza vaccination rate in RA patients was 14.8% in 2008, 19.8% in 2009 and 9.50% in 2010. Receiving influenza vaccine was associated with reduced risk of hospitalization for septicemia, bacteremia or viremia (hazards ratio [HR] = 0.65, 95% CI = 0.45-0.94), and lower risk of mortality (HR = 0.62, 95% CI = 0.39-0.97). The effectiveness was particularly significant in elderly patients. CONCLUSIONS: RA patients receiving influenza vaccine have significantly lower morbidity and mortality, particularly in elderly patients. Further studies are needed to explore effective policies to increase the vaccination rate in elderly RA patients.
30539352 Diastolic dysfunction in rheumatoid arthritis patients with low disease activity. 2019 Apr INTRODUCTION/OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk for congestive heart failure (CHF) and left ventricular diastolic dysfunction (LVDD), as compared to the general population. High disease activity is to be associated with higher incidence of cardiovascular disease (CVD), CHF, and mortality in RA patients. LVDD is not anticipated in RA patients without CVD symptoms and may be underdiagnosed especially in those with low disease activity. METHOD: The study group consisted of 70 RA patients (54 women, 16 men) with no CVD and 33 healthy controls, of comparable age. All RA patients had low disease activity (DAS28 ≤ 3.2) from 2 to 7 years. Laboratory and imaging assessments included metabolic, RA-related, and cardiovascular parameters. Echocardiographic and Doppler studies were conducted in patients and controls with assessment of ejection fraction (EF) and diastolic dysfunction (assessed as E/A ratio). RESULTS: The mean E/A ratio did not differ significantly between RA patients and healthy controls (1.08 (0.28) vs 0.99 (0.21), NS); comparable numbers of patients and controls had abnormal E/A (< 1.0) (26 (37.1%) vs 10 (30.3%), NS). Patients with decreased E/A were significantly older and had higher disease duration, activity, and presence of bone erosions than their RA counterparts with normal E/A. The mean EF was not significantly different in patients and controls. CONCLUSIONS: The prevalence of DD as expressed by E/A ratio in RA patients with continued low disease activity was not different from that of controls. Higher disease duration and severity may predispose to DD occurrence in patients with preserved EF.
30358109 Pharmacodynamic biomarkers and differential effects of TNF- and GM-CSF-targeting biologics 2019 Apr AIM: The aim of our study was to identify pharmacodynamic biomarkers and assess differential effects of tumor necrosis factor (TNF)- and non-TNF-targeting agents on rheumatoid arthritis (RA) patients with an inadequate response to anti-TNF agents (anti-TNF-IR) in comparison with biologic-naïve patients. METHODS: EARTH EXPLORER 2, a phase IIb trial, evaluated golimumab, an anti-TNF antibody, and mavrilimumab, an granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor antibody, in disease-modifying antirheumatic drug (DMARD)-IR and anti-TNF-IR patients. Our current study assessed peripheral protein markers and gene expression levels in association with clinical response post-treatment in two disease strata. RESULTS: Serum proteomics results indicated the existence of specific pharmacodynamic markers for golimumab and mavrilimumab, regardless of prior anti-TNF treatment. In contrast, both antibodies induced early and sustained suppression of RA disease markers, including interleukin (IL)-6, C-reactive protein, IL2RA, and matrix metalloproteinase 1, in DMARD-IR patients. Golimumab-induced early changes rapidly returned toward baseline concentrations in anti-TNF-IR patients, whereas mavrilimumab-induced changes were maintained through to day 169. RNA sequencing demonstrated gene expression changes at day 169 after administration of mavrilimumab but not golimumab in anti-TNF-IR patients. Additionally, receiver operating characteristic curve and regression analysis showed the association of early IL-6 change and subsequent clinical responses to golimumab in anti-TNF-IR patients. CONCLUSION: Our results revealed golimumab- and mavrilimumab-specific pharmacodynamic biomarkers, and demonstrated differential biomarker-treatment relationships in anti-TNF-IR and DMARD-IR patients, respectively. Early IL-6 change after anti-TNF antibody treatment may be a potential predictive biomarker for selection of different treatment regimens in anti-TNF-IR patients.
28967710 Personalized diet and exercise recommendations in early rheumatoid arthritis: A feasibilit 2018 Mar BACKGROUND: Physical activity and diet have a positive influence on disease activity and cardiovascular risk in patients with rheumatoid arthritis (RA). OBJECTIVE: We tested the feasibility and effect of a brief individualized counselling intervention on physical activity levels and fitness, and dietary intake, compared with standard of care. METHODS: Thirty patients with inflammatory arthritis (<1 year duration) were assigned to standard of care or the intervention, which consisted of individualized visits with a dietetic intern and physiotherapist at two time points, to review age-specific strategies on diet and exercise. Primary outcomes included anthropometric measurements (height, weight, waist and hip circumference), nutritional intake, physical activity (pedometer steps) and physical fitness. Disease activity measures and biochemical testing (blood pressure measurement, inflammatory markers, cholesterol profile and random glucose) were collected. The changes in these outcomes from baseline to 6 months were assessed using paired t-tests between groups. RESULTS: Thirteen patients in the intervention group and 10 in the control group completed the study. There were non-significant trends in improvements in physical activity, low-density lipoprotein cholesterol level and nutritional intake (vitamin C, iron, fibre, vitamin A and folate) in the intervention group. CONCLUSIONS: Poor enrolment and high dropout rates in this short-term study highlighted the difficulty of behavioural change. Those continuing in the study and who received the intervention demonstrated a non-significantly improved activity level and nutritional intake that may benefit long-term outcomes.
29516308 Transplantation and Alternatives to Treat Autoimmune Diseases. 2018 Transplantation is considered as one of the methods for the treatment of autoimmune diseases. There are different sorts of transplantation which improved the situation for the cure of different kinds of autoimmune diseases. Cord blood transplantation is favored over other transplant techniques. The propelled treatments incorporate interferon administrative elements and mesenchymal stromal cells for the management of immune system issue particularly in the treatment of rheumatoid joint inflammation. According to the studies conducted, it was proven that cord blood/UC mesenchymal cells along with DMARDs, without consistent organization expanded the level of administrative regulatory T-cells of the peripheral blood which might be a protected and huge technique for the treatment of patients experiencing rheumatoid joint inflammation. This review article focusses on different organ transplantation and alternative methods to treat autoimmune condition like rheumatoid arthritis. Using 3D printing and artificial intelligence are some of the recent trends that may be used for the management of autoimmune diseases.
28930550 Strategies for reducing inflammation and promoting bone repair in arthritis. 2018 Jan 1 Chronic forms of arthritis encompass many joint inflammatory disorders, including rheumatoid arthritis (RA), an autoimmune inflammatory disease, and osteoarthritis (OA), typically a 'wear and tear' condition that is now known to also have an inflammatory etiology. The impact of inflammation in the disease prognosis and joint degradation due to impaired repair mechanisms has long been recognized for RA, and now also for OA. Both forms of arthritis are prevalent chronic health conditions, and despite recent advances, their treatment still represents an unmet medical need because of safety and efficacy concerns with currently prescribed drugs. There is an urgent need to develop and test new drugs that selectively target inflamed joints and to control articular inflammation while preventing healthy tissue damage. The therapeutics developed for RA might be useful for OA, since studies in humans and animal models demonstrate a key role for chronic, low-grade inflammation in the pathogenesis of OA. In this review, we discuss current and emerging new therapies for management of inflammation and promotion of cartilage and/or bone repair in RA and OA.
28880683 RANKL: A therapeutic target for bone destruction in rheumatoid arthritis. 2018 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive joint destruction. Recent studies have indicated the critical involvement of osteoclasts in bone destruction in RA. The osteoclast differentiation factor receptor activator of NF-κB ligand (RANKL), which belongs to the tumor necrosis factor superfamily, plays a critical role in osteoclast differentiation and bone destruction in RA. Denosumab, an antibody against human RANKL, efficiently suppressed the progression of bone erosion in RA patients in randomized controlled studies, and is considered as a putative therapeutic option for preventing bone destruction in RA.
30014260 Fatigue in early, intensively treated and tight-controlled rheumatoid arthritis patients i 2018 Sep Fatigue has a large impact on quality of life and is still unmanageable for many patients. Study aims were describe (1) the prevalence and pattern of fatigue over time in patients with early rheumatoid arthritis under a treat-to-target strategy and (2) identify predictive factors for worsening and recovering of fatigue over time. Data from the tREACH study were used, comparing different treatment strategies with fatigue as secondary objective. Patient outcomes on fatigue, quality of life, depression, and coping were obtained every 6 months and clinically assessed every 3 months. Prediction of fatigue at 12 months was investigated with an ROC curve. Analysis was stratified into non-fatigue and fatigue at baseline. Logistic regression was used for the evolution of fatigue in relation with the covariates over time. Almost half of all patients (n = 246) had high fatigue levels at baseline, decreasing slightly over time. At 12 months, 43% of patients were fatigued; while 23% of the initially fatigued patients showed lower levels of fatigue, the fatigue level had increased in 15% of the initially non-fatigued patients. The strongest predictor of fatigue was the previous fatigue levels (AUC 0.89). Higher score on the depression scale and coping with limitations was associated with developing fatigue over time in the initially non-fatigued group. Despite a strict treat-to-target strategy, fatigue remained an overall problem during the first year of treatment, and was mainly predicted by its baseline status. In subgroups, a small additional effect of depression was seen. Monitoring fatigue and depression may be important in managing fatigue.
29298452 Have the Annual Trends of Total Knee Arthroplasty in Rheumatoid Arthritis Patients Changed 2018 Oct As the use of disease modifying antirheumatic drugs have increased, it remains unclear whether or not this has affected the rates of total knee arthroplasty (TKA) in rheumatoid arthritis (RA) patients. Therefore, the purpose of this study was to evaluate the annual trends of RA patients who underwent TKA. Specifically, we evaluated: (1) the annual trends of TKAs due to RA in the United States population; and (2) the annual trends in the proportion of TKAs due to RA in the United States. The Nationwide Inpatient Sample was used to identify all patients who underwent TKA between 2002 and 2013 (n = 6,492,873). Then, we identified TKA patients who had a diagnosis of RA, defined by the International Classification of Diseases, Ninth Revision (ICD-9) code 714.0. The incidence of TKAs with a diagnosis of RA in the United States was calculated using the U.S. population as the denominator. Regression models were used to analyze the annual trends of RA in patients who underwent TKA. A total of 209,332 RA patients were identified who underwent TKA. The annual prevalence of RA in patients who underwent TKA slightly increased, from 33.2 per 1,000 TKAs in 2002 to 35 per 1,000 TKAs in 2013 (R(2) = 0.254, p = 0.095). The annual number of TKAs with a diagnosis of RA increased by 93.1% from 11,618 to 22,430. After normalizing for the U.S. population, the incidence of TKAs with RA increased from 5.4 to 9.2 TKAs per 1 million U.S. adults (incidence rate ratio [IRR] = 1.05; 95% confidence interval [CI], 1.05-1.05; p < 0.001). In 2002, 11,618 (3.31%) TKAs, and in 2013, 22,430 (3.50%) TKAs were due to RA. The prevalence of RA in those who underwent TKA remained the same from 2002 to 2013 (coefficient = 0.02; 95% CI, -0.01 to 0.05; p = 0.095). The results of this study demonstrated that the rates of TKA performed in RA patients have remained relatively stable. Furthermore, there may have been a decline in the rate of RA patients undergoing TKA, due to an increase in the U.S. population by approximately 28.8 million during the study period.
30217121 Involvement of midkine in autoimmune and autoinflammatory diseases. 2019 Jul Midkine (MK) is a heparin-binding growth factor that markedly expressed during embryogenesis but downregulated to inconsiderable levels in healthy adults. However, MK is upregulated during tissue repair and in many pathologic conditions, mostly malignancies and inflammatory diseases. MK promotes a number of functions in target cells such as migration, proliferation, survival, growth, reproduction and repair, angiogenesis, and gene expression. It acts as a pro-inflammatory cytokine and contributes to chronic inflammation via promoting chemotaxis and tissue infiltration of neutrophils and macrophages. Furthermore, MK upregulated the production of various inflammatory mediators (i.e. interleukin (IL) 6 and IL8). Recent studies have demonstrated strong evidence that MK is involved in the onset and progression of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) and other autoimmune conditions such as multiple sclerosis (MS). Additionally, it has been shown that MK is overexpressed in two major clinically defined forms of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), which are classified as autoinflammatory diseases. Taken together, MK is involved in the pathogenesis of autoimmune and autoinflammatory diseases and may serve as an indicator and biomarker in these conditions. Furthermore, MK inhibitors are expected to contribute in the management of these diseases.
30343710 PBC and related extrahepatic diseases. 2018 Jun Patients with PBC have at least 60% of probability to have an autoimmune extrahepatic condition. The pathogenesis of these conditions includes a common mechanism involving both innate and adaptive immune responses targeting cholangiocytes and different extrahepatic tissues. The recent EASL guidelines recommend the management of these conditions, although detailed practical treatments have not been indicated. Autoimmune extrahepatic conditions may include: rheumatologic, endocrine, pulmonary, gastrointestinal, dermatologic diseases. This review aims to focus the most important extrahepatic autoimmune conditions associated to PBC with practical recommendation regarding diagnostic approach and management.
30306254 Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid 2018 Nov This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease. Using multiple logistic regression, we estimated the chance of early DMARD receipt based on age, sex, serotype and specialty of prescribing physician while controlling for region of residence. In total, 44% of incident RA patients received a DMARD prescription within the first year of disease. In multiple regression, younger patients (< 35 years) had 1.7-fold higher chances of receiving a csDMARD than patients aged ≥ 65 years [odds ratio (OR): 1.65 with 95% confidence interval (CI) 1.51-1.80] and almost tenfold higher chances to receive a bDMARD [OR (95% CI) 9.5 (8.0-11.3)]. Seropositivity and a visit to a rheumatologist were positively associated with DMARD initiation [OR (95% CI) 2.8 (2.6-2.9) and 5.9 (5.6-6.2) for csDMARDs, respectively]. Based on data covering 87% of the German population, the present study revealed that less than half of incident RA patients receive DMARDs within the first year of disease and that marked differences exist according to age. The study highlights the importance of involving a rheumatologist early in the management of RA.
29290168 The Economic Burden of ACPA-Positive Status Among Patients with Rheumatoid Arthritis. 2018 Jan BACKGROUND: Anticitrullinated protein antibodies (ACPAs) are serological biomarkers associated with early, rapidly progressing rheumatoid arthritis (RA), including more severe disease and joint damage. ACPA testing has become a routine tool for RA diagnosis and prognosis. Furthermore, treatment efficacy has been shown to vary by ACPA-positive status. However, it is not clear if the economic burden of patients with RA varies by ACPA status. OBJECTIVE: To determine if the economic burden of RA varies by patient ACPA status. METHODS: IMS PharMetrics Plus health insurance claims and electronic medical record (EMR) data from 2010-2015 were used to identify patients with incident RA. Patients were aged ≥ 18 years, had ≥ 1 inpatient or ≥ 2 outpatient claims reporting an RA diagnosis code (ICD-9-CM code 714.0), and had an anticyclic citrullinated peptide (anti-CCP; a surrogate of ACPA) antibody test within 6 months of diagnosis. Incident patients were defined as those who had no claims with an RA diagnosis code in the 6 months before the first observed RA diagnosis. The primary outcome of interest was RA-related medical expenditures, defined as the sum of payer- and patient-paid amounts for all claims with an RA diagnosis code. Secondary outcomes included health care utilization metrics such as treatment with a disease-modifying antirheumatic drug (DMARD) and physician visits. Generalized linear regression models were used for each outcome, controlling for ACPA-positive status (defined as anti-CCP ≥ 20 AU/mL), age, sex, and Charlson Comorbidity Index score as explanatory variables. RESULTS: Of 647,171 patients diagnosed with RA, 89,296 were incident cases, and 47% (n = 42,285) had an anti-CCP test. After restricting this sample to patients with a linked EMR and reported anti-CCP test result, 859 remained, with 24.7% (n = 212) being ACPA-positive. Compared with ACPA-negative patients, adjusted results showed that ACPA-positive patients were more likely to use either conventional (71.2% vs. 49.6%; P < 0.001) or biologic (20.3% vs. 11.8%; P < 0.001) DMARDs during the first year after diagnosis and had more physician visits (5.58 vs. 3.91 times per year; P < 0.001). Annual RA-associated total expenditures were $7,941 for ACPA-positive and $5,243 for ACPA-negative patients (Δ = $2,698; P = 0.002). RA-associated medical expenditures were $4,380 for ACPA-positive and $3,427 for ACPA-negative patients (Δ = $954; P = 0.168), whereas DMARD expenditures were $3,560 and $1,817, respectively (Δ = $1,743; P = 0.001). CONCLUSIONS: RA-related economic burden is higher for patients who are ACPA-positive compared with those who are ACPA-negative. Providers may wish to inform patients diagnosed with ACPA-positive RA about the likely future disease and economic burden in hopes that both stakeholders can be more proactive in addressing them. DISCLOSURES: Funding for this research was contributed by Bristol-Myers Squibb. Patel and Price are employees and stockholders of Bristol-Myers Squibb. Shafrin and Tebeka are employees of Precision Health Economics, a health care consulting firm that received funding from Bristol-Myers Squibb to conduct this study. Michaud has received a grant from Pfizer and is employed by the National Data Bank for Rheumatic Diseases, which has received funds from Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, and Regeneron. Study concept and design were contributed by Shafrin, Price, Patel, and Michaud. Shafrin, Price, and Patel collected the data, and all authors contributed equally to data analysis. The manuscript was written by Shafrin and Tebeka and revised by Shafrin, Price, Patel, and Michaud.
30338651 Target setting for lower limb joint surgery using the Timed Up and Go test in patients wit 2018 Oct OBJECTIVE: This prospective observational cohort study aimed to set targets for lower limb joint surgery based on the Timed Up and Go test (TUG), an objective functional outcome measure, in patients with established rheumatoid arthritis (RA). METHODS: We validated TUG as an outcome measure of lower limb joint surgery and compared it with changes in patient-reported outcomes, including the Health Assessment Questionnaire Disability Index (HAQ-DI) and European Quality of life scale with five dimensions (EQ-5D). Changes in these outcomes were compared by performed surgery and by achievement of the minimal clinically important difference (MCID) for EQ-5D using univariate analysis of variance. Associations between TUG and HAQ remission (HAQ-DI ≤0.5) were determined using logistic regression analysis. Cut-off values of TUG at baseline and 6 months after surgery for HAQ remission were determined using receiver operating characteristic curves. RESULTS: A total of 126 patients were analyzed. Mean age, HAQ-DI, and TUG were 65.4 years, 1.036, and 12.8 seconds, respectively. After surgery, patients showed improvements in TUG as well as HAQ-DI. TUG at 6 months after surgery was significantly associated with HAQ remission (adjusted OR: 0.78; 95% CI: 0.65-0.93). TUG cut-off values at baseline and 6 months after surgery for achieving HAQ remission were 12.1 and 8.8 seconds, respectively. Significant improvements in TUG (∆TUG, 3.7 seconds) were associated with achievement of the MCID for EQ-5D (≥0.05) at 6 months after surgery. CONCLUSION: Timed Up and Go test is a useful tool for assessing the outcome of lower limb joint surgery in RA patients. We propose that TUG ≤9 seconds could be an objective target for achieving good physical function after lower limb joint surgery.