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ID PMID Title PublicationDate abstract
26288664 B-cell survival factors in autoimmune rheumatic disorders. 2015 Aug Autoimmune rheumatic disorders have complex etiopathogenetic mechanisms in which B cells play a central role. The importance of factors stimulating B cells, notably the B-cell activating factor (BAFF) and A proliferation inducing ligand (APRIL) axis is now recognized. BAFF and APRIL are cytokines essential for B-cell proliferation and survival from the immature stages to the development of plasma cells. Their levels are increased in some subsets of patients with autoimmune disorders. Several recent biologic drugs have been developed to block this axis, namely belimumab [already licensed for systemic lupus erythematosus (SLE) treatment], tabalumab, atacicept and blisibimod. Many clinical trials to evaluate the safety and efficacy of these drugs in several autoimmune disorders are ongoing, or have been completed recently. This review updates the information on the use of biologic agents blocking BAFF/APRIL for patients with SLE, rheumatoid arthritis, Sjögren's syndrome and myositis.
26078980 Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheime 2015 Bone is sensitive to overactive immune responses, which initiate the onset of inflammatory bone disorders, such as rheumatoid arthritis and periodontitis, resulting in a significant systemic inflammatory response. On the other hand, neuroinflammation is strongly implicated in Alzheimer's disease (AD), which can be enhanced by systemic inflammation, such as that due to cardiovascular disease and diabetes. There is growing clinical evidence supporting the concept that rheumatoid arthritis and periodontitis are positively linked to AD, suggesting that inflammatory bone disorders are risk factors for this condition. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to brain-resident microglia. More importantly, senescent-type, but not juvenile-type, microglia provoke neuroinflammation in response to systemic inflammation. Because the prevalence of rheumatoid arthritis and periodontitis increases with age, inflammatory bone disorders may be significant sources of covert systemic inflammation among elderly people. The present review article highlights our current understanding of the link between inflammatory bone disorders and AD with a special focus on microglia aging.
27730043 Methotrexate-induced nonhealing cutaneous ulcers in a nonpsoriatic patient without pancyto 2016 Sep Methotrexate forms one of the main drugs in the pharmacological management of rheumatoid arthritis, psoriasis, and some neoplastic diseases. Methotrexate rarely causes cutaneous ulceration and most cases are reported in patients with psoriasis and have been accompanied by pancytopenia. The author here reports occurrence of multiple (two) cutaneous ulcers due to methotrexate in a nonpsoriatic patient. The patient was on methotrexate for seronegative rheumatoid arthritis for 10 years. To the best of the Author's knowledge, this is a rare case of cutaneous ulceration due to methotrexate in a nonpsoriatic patient reported in the literature so far, and probably one of its kind without pancytopenia or other hematological abnormalities. Stopping this medication led to complete healing of the ulcerated lesion in about four to six weeks.
26034476 Adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis. 2015 Jan Lipodystrophy is a group of metabolic disorders, possibly caused by autoimmune disease. In this report, we describe a case of adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis without a family history. Interestingly, immunohistochemical staining revealed dense infiltration of IL-27-producing cells as well as MMP-7-and MMP-28-expressing cells, both of which have been reported to facilitate the development of autoimmune disease. Our present case might suggest possible mechanisms for acquired partial lipodystrophy.
27857821 Carotid Artery Atherosclerosis in Patients with Active Rheumatoid Arthritis: Predictors of 2016 INTRODUCTION: This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA). METHODS: Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)≥8 OR SJC plus TJC≥4 with elevated acute phase reactants) and were enrolled (27 female; mean age 59.3±9.8years). Patients using lipid lowering drugs and uncontrolled comorbidities were excluded. RESULTS: Atherosclerotic plaque occurred in 35% and arterial wall hypertrophy (IMT≥0.6mm) in 86% of patients. Most (68%) had an abnormal lipid profile characterized by reduced HDL and/or increased total cholesterol/HDL index, which was adversely affected by disease activity. Stepwise binary logistic regression analysis showed that Framingham risk score (OR=1.155, 95%CI:1.002-1.332, p=0.046) and ESR (OR=1.148, 95%CI:1.015-1.299, p=0.028) predicted plaque burden most strongly. Plaque progression was significantly associated with baseline higher hsCRP, ESR, and heavy smoking, but only hsCRP predicted plaque growth in multivariate regression analysis (p=0.004); and hsCRP was related to higher disease activity (r=0.443, p=0.016), LDL (r=0.544, p=0.007), and smoking (r=0.384, p=0.04). CONCLUSION: RA-related inflammation contributed to augmented CV burden in RA and might mediate its effect on atherosclerosis through hsCRP and modulation of the traditional CV risk factors, such as dyslipidemia.
30375576 Caregiver Burden of Rheumatoid Arthritis Patients With Self-Care Deficit in China: A Cross 2016 Dec OBJECTIVES: This study aims to investigate the level of caregiver burden of Chinese rheumatoid arthritis (RA) patients with self-care deficit. PATIENTS AND METHODS: This cross-sectional study included a total of 65 caregivers (30 males, 35 females; mean age 52 years; range 20 to 79 years) of 65 RA inpatients (9 males, 56 females; mean age 59 years; range 20 to 85 years) with self-care deficit. Demographic data of patients and their respective caregivers were collected. The level of caregiver burden was defined using Caregiver Burden Inventory, a 24-item-five-domain survey tool. Correlation between different demographic factors and caregiver burden was analyzed. Predictive factors for burden level were also investigated. RESULTS: A mean Caregiver Burden Inventory score of 44.0±4.0 was observed among caregivers of Chinese RA patients with self-care deficit. Among the five Caregiver Burden Inventory domains, developmental burden scored the highest (11.7±1.4), while physical burden scored the lowest (6.7±1.0). Among various demographic factors, patients' age (r=0.306, p=0.013) and health insurance coverage (r=-0.246, p=0.04) were correlated with the level of caregiver burden. Besides, caregiver's educational level (r=-0.316, p=0.01), relationship of caregiver with the patient (r=0.355, p=0.004), and whether or not the caregiver lived with the patient (r=0.362, p=0.003) were also significant factors. Predictive factors for caregiver burden of RA patients were identified as patient's health insurance coverage and caregiver's relationship with the patient, in agreement with the correlation analysis. CONCLUSION: Since caregiver burden may contribute to adverse health outcomes, supportive interventions should be established to target Chinese RA patients with self-care deficit and their caregivers to consolidate the sustainable care provided both at hospital and home.
26884917 Application of contrast-enhanced ultrasonography and ultrasonography scores in rheumatoid 2015 OBJECTIVE: To investigate diagnostic value of ultrasonography scores (US) and contrast-enhanced ultrasonography (CEUS) in evaluating rheumatoid arthritis (RA) activity. METHODS: 39 patients with RA were included and the metacarpophalangeal, proximal interphalangeal, wrist, elbow and knee joints of them were examined by high frequency ultrasound. The severe joints and the related indexes (synovial thickness, synovial blood flow, joint effusion and bone erosion) were exposed. Then scores (0~3) were obtained and the sum was calculated. For 12 patients of the 39, 2.4 ml SonoVue was intravenously injected with observation of synovial enhancing. ROIs time-intensity curve (TIC) was obtained and the parameters including area under curve (AUC), peak intensity (PI) and time to peak (TTP) were analyzed. For 39 patients, the relationships among each parameters, ultrasonography scores, DAS28 scores and biochemical examinations (ESR, CRP, RF, anti-CCP) were analyzed. RESULTS: The US were significantly correlated with DAS28 Scores (r=0.823, P<0.01=. The correlation between US and CRP was better than that between DAS28 scores and CRP (rUS =0.692, rDAS28=0.526, P<0.01). The synovial thickness in US were correlated with DAS28 Scores and biochemical examinations (ESR, CRP) (rDAS28=0.852, rESR=0.779, rCRP=0.587, P<0.01. The AUC and PI in CEUS were significantly correlated with US (rAUC=0.832, rPI=0.809, P<0.01=. The correlations among AUC, PI and ESR were better than that between US and ESR (rAUC=0.907, rPI=0.851, rUS=0.836, P<0.01=. The correlations among AUC, PI and CRP were better than that between US and CRP (rAUC=0.855, rPI=0.854, rUS=0.692, P<0.01. CONCLUSIONS: US was almost identical with DAS28 Scores and biochemical examinations (ESR, CRP) in diagnosis of RA activity, while CEUS was almost identical with DAS28 Scores and biochemical examinations (ESR, CRP). In diagnosis of RA, US may be better than DAS28 Scores, while CEUS better than US. Both of them were useful for evaluation of RA activity.
26862353 Determinants of Disability in Rheumatoid Arthritis: A Community-Based Cohort Study. 2015 Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the 'patient-acceptable symptom state' for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ ≥1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms.
26834936 Novel Adherence Measures for Infusible Therapeutic Agents Indicated for Rheumatoid Arthrit 2015 Dec BACKGROUND: Published studies on adherence to biologic medications show that many types of calculation methods are used. However, infused biologics are not well-suited to typical measures of adherence, such as proportion of days covered. OBJECTIVE: To construct and assess 7 novel adherence measures potentially applicable to infusible biologic agents and compare outcomes for 2 infusible biologics used for the treatment of patients with rheumatoid arthritis (RA). METHODS: Adults (aged ≥18 years) diagnosed with RA (ie, 2 or more 714.x claims) who received ≥24 months of continuous medical and pharmacy eligibility and who started taking abatacept or infliximab therapy were selected from a large commercial insurer database of medical and pharmacy claims. The 7 new adherence measures included cumulative amount of time with a refill gap ≥20% (CG20) beyond the expected infusion interval, cumulative time off treatment, days of uninterrupted use (DoUU), observed versus expected refill ratio (OvERR), repeated observations of underuse (RoUU), variance in time between infusions, and time to discontinuation (TTD). Mean observed infusion intervals were calculated and served as a reference measure of adherence. RESULTS: The mean maintenance intervals approximated recommended guidelines. The mean observed infusion interval for abatacept recipients was 33 days (recommended, 28 days); it was 53 days (recommended, 56 days) for patients receiving infliximab. Three measures demonstrated a significant positive relationship to the mean observed infusion interval-CG20 (r = .258), DoUU (r = .212), and TTD (r = .081; P <.05). OvERR (r = -.072) and RoUU (r = -.189; P <.05) showed significant negative correlations. Real-world comparisons showed that adherence was significantly (P <.001) greater for the infliximab group according to most measures. CONCLUSION: New measures of adherence correlate significantly with mean maintenance intervals. Future studies should examine relationships between these adherence measures and clinically relevant end points and/or cost outcomes to determine their predictive utility. Alternative methods of reporting adherence may have greater clinical significance than traditional measures.
26229559 Prevalence and risk factors of asymptomatic bronchiectasis in patients with rheumatoid art 2015 Jul INTRODUCTION AND OBJECTIVES: Bronchiectasis is a pulmonary manifestation that often occurs in individuals with rheumatoid arthritis (RA). Nevertheless, the prevalence of bronchiectasis in RA patients and predictors of its development/progression remain ill-defined. Our objective was to investigate the prevalence of bronchiectasis in a group of RA patients and examine possible clinical or biochemical risk factors that might contribute to its development. METHODS: This was an observational study analyzing 100 RA patients with no pulmonary symptoms selected from King Abdulaziz University Hospital in the Western region of Saudi Arabia from October 2013 to 2014. Demographic, clinical and laboratory information were collected for all patients. Diagnosis was based on the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification system, and disease activity was assessed using the 28-Joint Disease Activity Score Index with C-reactive protein; high-resolution computed tomography chest scans were performed. The prevalence of bronchiectasis was recorded and its association with different risk factors was examined using standard statistical methods. RESULTS: All 100 patients fulfilled the ACR and EULAR classification criteria for RA diagnosis. Their mean age was 51.05 ± 13.5 years, disease duration was 6.19 ± 6.4 years and disease activity index was 4 ± 1.3 (moderate activity). A total of 35 (35%) patients developed bronchiectasis. Notably, we observed significant positive associations of bronchiectasis with age, disease duration and male gender (P < 0.001, P = 0.006, P = 0.028, respectively). CONCLUSIONS: Asymptomatic bronchiectasis represents a common complication in moderately active RA patients within the Western Region of Saudi Arabia. Furthermore, several predictors of bronchiectasis development were identified, which can contribute to effective risk stratification in RA patients. Further prospective studies are needed to detect the prognosis of asymptomatic bronchiectasis in RA patients.
26180748 Vascular disease as a cause of death in patients with severe disability due to osteoarthri 2015 OBJECTIVES: The mechanism of the increased risk of cardiovascular disease in rheumatoid arthritis (RA) remains uncertain. We had the opportunity to compare the causes and ages of death in a population of osteoarthritis (OA) and RA patients who had had similar lower limb disability. METHODS: Death certificates were sought for a population of OA and RA patients who had had knee joint replacements performed by a single orthopaedic surgeon over a 10 year period with a minimum follow up period of 18 years. Primary cause of death was assigned by a blinded clinician and compared between the populations. Competing risk analysis was used to compare RA and OA populations for cardiovascular deaths. RESULTS: The total population was 607 (294 OA; 313 RA). 85% (249) of the OA and 79% (246) of the RA patients had deceased at the time of study in 2008. 85% of the death certificates were found. The RA patients were operated an average of 7.5 years younger and also died 7.5 years younger. The causes of death were similar in the two populations. The ages at death were consistently and similarly older for the OA group for all causes of death. There was a 9% increased risk of cardiovascular death in the RA group but this was not statistically different from the OA group. CONCLUSIONS: OA and RA patients, controlled for lower limb disability, have similar causes of death including cardiovascular disease. However, the RA patients died significantly younger. Cause of death is likely to be related to things that OA and RA share, such as disability and some treatments e.g. NSAIDs, whereas age at death relates to differences, such as age of onset and inflammation.
27747493 Refining the Management of Rheumatoid Arthritis: the Benefits of Subcutaneous Tocilizumab. 2015 Jun Rheumatoid arthritis (RA) is a chronic systemic autoimmune condition which affects approximately 1% of the adult population worldwide and is characterized by joint inflammation, with extra-articular features being common. Interleukin 6 (IL-6) is one of the chief pro-inflammatory cytokines found in the joints and sera of patients with RA. Increased levels of IL-6 correlate with inflammation, disease activity, and radiological damage. RA treatment should focus on minimizing the signs and symptoms of disease (pain, stiffness, and swelling of the joints) and on preventing or minimizing joint damage to preserve functionality and quality of life. The benefits of early, intensive intervention are now acknowledged, with all patients with newly diagnosed, active RA being started on methotrexate (MTX) monotherapy or combination therapy. Lack of efficacy, intolerance, and/or toxicity can lead to discontinuation of this drug, and there is a need for exploring further treatment options. In the UK, patients with persistently high disease activity who have failed at least two conventional disease-modifying agents (DMARDs) including MTX may qualify for biologic therapy. Numerous trials have shown intravenous (IV) tocilizumab (TCZ), a biologic drug targeting and inhibiting IL-6, to be effective for controlling inflammation in RA, with an acceptable safety profile. Its superiority in monotherapy when compared with other biologic agents makes it the drug of choice for patients who are intolerant or have contraindications to traditional DMARDs. However, one of the drawbacks of IV TCZ is the requirement for monthly infusions, which is inherently inconvenient for the patient and associated with increased cost. Subcutaneous (SC) TCZ has now been approved following two clinical trials which showed similar efficacy and safety compared to IV TCZ, and better efficacy compared to placebo (SUMMACTA and BREVACTA trials, respectively). Respiratory infections are the most common side effects in patients receiving SC TCZ. Advantages of SC formulations include convenience and reduced cost compared with IV therapies. Overall, patients tend to have a preference for SC over IV administration of medications. Close monitoring of patients should be undertaken in all cases, paying particular attention to the full blood count, liver enzymes, and cholesterol levels.
27649959 [Periprosthetic infections in patients with rheumatism : A challenge]. 2016 Dec The increasing number of implantations will lead to more periprosthetic infections. Periprosthetic infections in patients with rheumatism, who are often undergoing immunosuppressive treatment, represent a challenge for the treating physicians. The optimal care and treatment therefore necessitate an interdisciplinary agreement between orthopedic surgeons, specialists for infections and rheumatologists.
27241704 Biosimilars in rheumatology: understanding the rigor of their development. 2017 Feb This article examines the current landscape of biosimilar development in rheumatology. As misperceptions about biosimilars exist regarding their comparability to the reference products for clinical use, we review the development paradigm with the goal of improving rheumatologists' understanding of the rigor with which biosimilars are developed. With an emphasis on European Union and US markets, it gives an overview of some of the challenges and issues related to biosimilar development that need to be considered by rheumatologists in this increasingly growing therapeutic space.
27107513 New biological therapies in Sjögren's syndrome. 2015 Dec Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by dryness and systemic involvement in more than a third of the patients. Patient management has suffered from the lack of effective treatments. However, progresses made in the understanding of pSS pathogenesis have allowed a move to a more targeted approach to therapeutic intervention. Given the key role of chronic B cell activation, B cell-targeted therapies were the first candidate. New pathways are currently investigated including costimulation and ectopic germinal centre formation. In this review, we have summarized the new tools available in clinical research in the field of pSS, the current evidence regarding B cell-targeted therapies and an overview of the promising drugs in the pipeline.
27747522 Emerging Therapies for Rheumatoid Arthritis. 2016 Jun Diverse strategies to develop novel treatments for rheumatoid arthritis which specifically target those patients who do not respond to available medications, including biologics, are currently being explored. New potential therapeutic approaches which may become available as part of standard therapeutic regimens include the propagation of regulatory T cells and-in the future-of regulatory B cells. New biologic disease-modifying antirheumatic drugs (b-DMARDs) against interleukin-17 and -6, granulocyte-macrophage colony-stimulating factor, and complement component 5 are now standard components of clinical treatment programs. In addition, recent data indicate that bispecific monoclonal antibody therapies may be more effective than monoclonal antibody monotherapies. It is also becoming apparent that the use of more toxic b-DMARDs against B cells, a therapeutic strategy already being applied in the treatment of hematological diseases, may also be efficacious for treating B cell-mediated autoimmune diseases. Undoubtedly, more small molecules will be developed in the future, and combination therapies with, for example, kinase inhibitors and b-DMARDs, will most likely be tested. Finally, immunoproteasome inhibitors will become available for patients with B cell-mediated autoimmunities, which are refractory to currently available treatment options. The new and exciting extension of current treatment options for rheumatoid arthritis, biosimilars, will not be discussed in this review as details on these agents are available in recently published reports.
25815013 Intertoe Squamous Cell Carcinoma Developed in a Patient with Rheumatoid Arthritis under Et 2015 The use of tumor necrosis factor-α (TNF-α) inhibitors in the treatment of various inflammatory conditions has altered the field of medical therapeutics. Squamous cell carcinoma is the second most common cancer of the skin, usually affecting sun-exposed areas of the body. We present here the case of a 75-year-old woman with rheumatoid arthritis, who developed an intertoe squamous cell carcinoma (SCC) of the right foot. According to her history, she received etanercept and methotrexate for 5 years for rheumatoid arthritis. The rare localization of this cancer could suggest a possible linkage of the malignancy to the chronic intake of anti-TNF-α treatment. This is the first reported case of an interdigital SCC developed under the use of an anti-TNF-α agent.
25670881 Safety of biologics in rheumatoid arthritis: data from randomized controlled trials and re 2015 Over the past decade, the use of biologics has significantly changed the management of rheumatoid arthritis (RA). Biologics selectively target components of the immune system, resulting in better disease control. However, the growing use of biologics in RA has increased safety concerns among rheumatologists. Randomized controlled trials (RCTs) and registries are the most reliable sources of clinical safety data. Although safety data from RCTs provide certain insights into the clinical safety profile of an agent, strict constraints in study design (eg, exclusion criteria and restrictive treatment protocols) often do not accurately reflect possible safety issues in the use of the agent, either in the clinical setting or over long-term treatment. Registries, on the other hand, are not restrictive regarding patient enrollment, making them more reliable in evaluating long-term safety. A number of registries have been established globally: in Europe, the United States, and Asia. However, the availability of registry data from Eastern Europe is lacking. The notable exceptions so far are registries from the Czech Republic (ATTRA, a registry of patients treated with anti-tumor necrosis factor-alpha drugs) and Serbia (National registry of patients with rheumatoid arthritis in Serbia [NARRAS]). The current report provides an overview of safety data with biologics in RA from RCTs and registries. Availability of regional safety data from Eastern Europe is of great importance to its clinicians for making evidence-based treatment decisions in RA.
27843301 Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-ch 2016 BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) used in second-line treatment of rheumatoid arthritis (RA) are administered parenterally. However, so-called targeted synthetic DMARDs (tsDMARDs) - developed more recently - offer alternative (ie, oral) administration forms in second-line treatment. Since bDMARDs and tsDMARDs can be regarded as equal in terms of efficacy, the present study examines whether such characteristics as route of administration drive RA patients' treatment choice. This may ultimately suggest superiority of some second-line DMARDs over equally effective options, at least according to RA-patient preferences. OBJECTIVE: The current study assessed the importance of oral administration among other treatment characteristics differing between available second-line DMARDs for RA patients' preferences using a discrete-choice experiment (DCE). MATERIALS AND METHODS: The DCE involved scenarios of three hypothetical treatment options in a d-efficient design with varying levels of key attributes (route and frequency of administration, time till onset of drug effect, combination therapy, possible side effects), as defined by focus groups. Further patient characteristics were recorded by an accompanying questionnaire. In the DCE, patients were asked to choose best and worst options (best-worst scaling). Results were analyzed by count analysis and adjusted regression analysis. RESULTS: A total of 1,588 subjects completed the DCE and were eligible for final analyses. Across all characteristics included in the DCE, "oral administration" was most desired and "intravenous infusion" was most strongly rejected. This was followed by "no combination with methotrexate" being strongly preferred and "intake every 1-2 weeks" being strongly rejected. On average, levels of route of administration showed strongest influences on patients' decisions in post hoc bootstrapping analysis. CONCLUSION: According to the results, an oral DMARD that does not have to be combined with methotrexate and is not administered (only) every 1-2 weeks appears a highly favorable treatment option for patients with RA. DMARDs meeting these preferences may increase compliance and adherence in RA treatment.
27478728 Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-sc 2016 OBJECTIVES: To study risk for cardiovascular disease (CVD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We used a Medical Data Vision database mainly composed of health insurance claim data and diagnosis-procedure combination data from Japan. Patients with RA diagnosed from April 2011 to March 2014 at 71 hospitals were identified with the International Classification of Diseases 10th revision (ICD-10) and history of anti-RA drug prescription. Hospitalizations for CVD including ischemic heart disease, heart failure, and stroke were identified by a combination of diagnosis (ICD-10) and diagnostic procedures. CVD incidence rate ratio (IRR) for RA versus osteoarthritis was calculated. Risk factors were analyzed using univariate and multivariate Cox proportional hazard models with baseline C-reactive protein (CRP) and traditional risk factors as covariates. RESULTS: We identified 8658 patients with RA. The age-sex adjusted IRR for RA versus osteoarthritis was high for total CVD [2.12; 95 % confidence interval (CI) 1.93-2.32], ischemic heart disease (2.16; 95 % CI 1.86-2.50), heart failure (2.34; 95 % CI 2.07-2.65), and stroke (1.68; 95 % CI 1.41-2.00). Risk factor analysis showed a tendency for cardiovascular risk to increase with higher baseline CRP, although the difference was not statistically significant (hazard ratio 1.43; 95 % CI 0.99-2.07). CONCLUSION: Our study indicates an increased risk for CVD and an association between systemic inflammation and CVD in Japanese RA patients.