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ID PMID Title PublicationDate abstract
22833186 Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoi 2012 Nov OBJECTIVE: To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs. METHODS: We performed a systematic search in Medline via PubMed, the Cochrane Central Register of Controlled Trials, EMBase via OVID, the Institute for Scientific Information Web of Science, and other sources. Eligible trials were parallel-group, randomized, placebo-controlled trials of oral NSAID therapy in RA patients for which there were extractable CRP data. Standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated from the differences in means of CRP levels between groups (active treatment minus placebo) divided by the pooled SDs. For the meta-analysis, a random-effects model was used to estimate the overall change in CRP level, and stratified analysis was used to examine differences among NSAIDs. RESULTS: We included 19 trials of 10 different NSAIDs. Overall, NSAIDs showed no effect on the CRP level (SMD 0.01 [95% CI -0.03, 0.06], P = 0.62). However, the prespecified stratified analysis indicated varying effects on the CRP level according to the different NSAIDs; lumiracoxib caused a statistically significant and consistent (I(2) = 0%) increase in the CRP level (SMD 0.13 [95% CI 0.01, 0.25], P = 0.037), whereas naproxen caused a statistically significant and consistent (I(2) = 0%) decrease in the CRP level (SMD -0.11 [95% CI -0.20, -0.02], P = 0.022). CONCLUSION: Overall, NSAIDs have no effect on the CRP level. However, the nonselective NSAID naproxen was associated with a significant decrease in the CRP level, whereas the cyclooxygenase 2-selective NSAID lumiracoxib was associated with a significant increase in the CRP level. This finding is interesting considering the suspected influence of NSAIDs on cardiovascular complications.
23072761 Systematic literature review on economic implications and pharmacoeconomic issues of rheum 2012 Jul OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.
22249163 What is the clinical relevance of erosions and joint space narrowing in RA? 2012 Jan 17 The association between joint damage and disability in rheumatoid arthritis (RA), especially in the later stages of disease, is a main reason why radiographic joint damage is a common and valid outcome measure in RA clinical trials. Most studies have assessed the effect of global joint damage, which has limited our knowledge regarding the individual effects of erosions and cartilage damage on physical function. However, recent data have indicated that joint space narrowing is more closely related to functional status than erosions. Modern imaging techniques that provide improved assessment of the cartilage itself, instead of only joint space narrowing, might help disentangle the separate associations of erosive bone damage and cartilage damage with physical function in patients with RA. The aim of this article is to discuss the current knowledge within this field and the clinical consequences thereof.
23227607 [Goals of therapy in rheumatoid arthritis]. 2012 Oct A better definition of goals of therapy has deeply changed the prognosis of rheumatoid arthritis. The main goal is the early control of joint inflammation reaching, if possible, remission in early arthritis and, in later cases, low disease activity. To target such a low activity, a tight control with therapeutic adjustment is necessary. The other goals derive from the control of inflammatory activity: reduction of progression and, if possible, stop of structural damage tightly linked to inflammation; control of functional consequences related mainly to the addition of inflammatory component and structural damage; control of cardio-vascular risk factors responsible of 30-50% of deaths and finally protection of bone.
21898059 Rheumatoid arthritis in patients with hemoglobinopathies. 2012 Sep Rheumatoid arthritis (RA) in patients suffering from hemoglobinopathies is an important clinical problem, but the correlation between these diseases is still imperfectly known. The aim of this study was to analyze the clinical, serological and radiological characteristics of RA occurring in patients with hemoglobinopathies (thalassemia major, thalassemia intermedia and sickle-cell disease). In a single institution, in an adult cohort of 90 patients with hemoglobinopathies, we investigated retrospectively medical records of the patients. We evaluated the clinical findings, the autoantibodies and the radiological progression of patients who were diagnosed with RA according the American College of Rheumatology (ACR) criteria for RA. There were found 4 patients, with thalassemia major, who fulfilling the ACR criteria for RA. The clinical picture of the patients revealed a mild form of arthritis of the knees, shoulders, wrist and hands, while one patient had episcleritis. All patients had radiological damage compatible with RA (Larsen's score, 28.75 ± 29). All had positive rheumatoid factor, while anti-cyclic citrullinated peptide antibodies were positive in 1 patient. Three patients received steroid treatment and one immunosuppressive agent (methotrexate). True RA with low frequency of extra-articular manifestations is described. The diagnosis of RA must be suspected in patients with hemoglobinopathies picture and chronic arthritis of small joints.
23090369 Epidemiological profile of patients with extra-articular manifestations of rheumatoid arth 2012 Oct OBJECTIVES: To describe the epidemiological profile of patients with extra-articular manifestations of rheumatoid arthritis (ExRA) from an university-affiliated rheumatology center; to report the prevalence of ExRA and to compare it with available data; and to identify, if possible, ExRA predictors. METHODS: This study reviewed 262 medical charts of patients previously diagnosed with rheumatoid arthritis (RA) according to the 1987 American College of Rheumatology criteria, and attending that rheumatology center in 2010. The statistical analysis comprised simple mathematical calculations, Student t and chi-square tests, and a significance level of 5% (α= 0.05). RESULTS: During the course of the disease, 120 patients (45.8%) had ExRA. Pulmonary manifestation, rheumatoid nodules and Sjögren's syndrome were the most common manifestations found. Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in most patients tested. Most patients were classified as Steinbrocker functional classes 1 and 2. The mean DAS-28 was 3.629, and the mean HAQ score, 1.12. Patients with ExRA had longer disease duration (P < 0.05), and current smoking habit associated with the presence of ExRA (P < 0.05). CONCLUSIONS: The prevalence of ExRA during disease course was 45.8%, and current smoking habit correlated with the presence of ExRA.
21453269 Clinical applications of autoimmunity to citrullinated proteins in rheumatoid arthritis, f 2011 May Rheumatoid arthritis (RA), although widely considered to be the most commonly occurring autoimmune disease, has only truly been substantiated as a distinct autoimmune disease very recently. The lack of understanding of the specific autoimmune system/s at work in rheumatoid patients resulted in an absence of robust diagnostic tools and had meant that the rational choice for use and design of therapy was based on broad-spectrum immunosuppression. The revelation that the autoimmune response specific for patients with RA is to particular protein antigens bearing the post-translational modification 'citrulline' has therefore revolutionized diagnostics and has helped explain why patients carrying particular MHC alleles are predisposed to the disease. The last two decades have seen the characterization of citrullinated antigens targeted by both antibodies and T cells in rheumatoid patients. In more recent years, we have also witnessed the success of biological therapies in the treatment of RA that specifically target T cells and B cells. Ongoing mapping of antibody targets is increasing the percentage of patients who can be definitively diagnosed with, and prognosed to develop, RA. These advances have led to a great number of patents for citrullinated peptides that have been and may be, in the coming years, used in diagnostic test kits. More recently, characterization of T cell targets (citrullinated peptides) has resulted in the patenting of peptides that could be used in antigen specific therapy. This review focuses on the characterization of the autoimmune response to citrullinated protein targets in RA and how the community is translating this knowledge to improve diagnostics, prognostics and therapy.
23013846 Subacromial bursitis with giant rice bodies as initial presentation of rheumatoid arthriti 2012 Oct Rice body formation is a nonspecific response to chronic synovial inflammation associated with tuberculous arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, seronegative inflammatory arthritis, and even osteoarthritis. Such bodies were termed rice bodies because of their close resemblance to grains of polished white rice. We present a case report of a middle-aged woman with right shoulder subacromial/subdeltoid bursitis with giant rice body formation as her initial presentation of rheumatoid arthritis. Her right shoulder symptoms resolved after subacromial and subdeltoid bursectomy and removal of the rice bodies. She subsequently developed inflammatory arthritis of other joints, met the criteria for rheumatoid arthritis, and has been treated medically.
23265058 [The comparative evaluation of the diagnostic value of methods of detection of antibodies 2012 Oct The hyper production of large specter of autoantibodies, primarily rheumatoid factors and antibodies to citrullinized proteins, is a characteristic sign of rheumatoid arthritis. The detection of these antibodies plays an important role in diagnosing the disease, especially on its early stages. The study compared the diagnostic accuracy of different methods of detection of antibodies to citrullinized proteins under rheumatoid arthritis. The examined sample included 144 patients aged 33-58 years with reliable diagnosis of rheumatoid arthritis. The patients with systemic lupus erythematous, osteoarthritis, psoriatic arthritis, OVERLAP syndrome, ankylosing spondylitis and conditionally healthy donors consisted the comparative group. To detect antibodies to citrullinized proteins the methods of enzyme immunoassay, electrochemiluminescence, immunochromatography were applied. The study demonstrated that all the methods of detection of antibodies to citrullinized proteins have adequate diagnostic value to be implemented both in a routine clinical diagnostic practice and on the stage of screening of patients.
22952388 Improved early identification of arthritis: evaluating the efficacy of Early Arthritis Rec 2013 Aug OBJECTIVE: Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12 weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP). In order to reduce delay of GPs in identifying early arthritis, we initiated an Early Arthritis Recognition Clinic (EARC). METHODS: EARCs were initiated at the Leiden and Groningen University Medical Centers. At this EARC, patients filled in a questionnaire about their symptoms, followed by a short visit with only a full joint examination by an experienced rheumatologist. If arthritis was present the patient got an appointment the same week at the regular outpatient clinic. The main outcome parameter was the GP-delay; the secondary outcome parameter was the total delay. In both centres, patients included in early arthritis clinics that had arrived via regular referrals served as control group. RESULTS: Four hundred patients visited the Leiden EARC and 212 patients the Groningen EARC. Arthritis was detected in 42% and 49% respectively. The median GP-delay for these arthritis patients was 2.0 (0.4-7.3) and 2.0 (0.4-10.0) weeks and the median total delay 8.6 (3.6-22.3) and 10.6 (3.1-30.8) weeks respectively. At these two clinics 59% and 51% of all arthritis patients and 65% and 53% of the patients that were subsequently diagnosed with undifferentiated arthritis or RA were seen within 12 weeks after symptom onset. In the Leiden and Groningen control groups that arrived via regular referrals, only 32% and 38% were seen within 12 weeks time. CONCLUSIONS: The EARC increased the early identification of arthritis and RA.
22417647 Value of self-performed joint counts in rheumatoid arthritis patients near remission. 2012 Mar 14 INTRODUCTION: To determine the validity and reliability of patients' self-performed joint counts compared to joint counts by professional assessors in rheumatoid arthritis (RA) patients in different disease activity states. METHODS: In patients with established RA we determined the inter-rater reliability of joint counts performed by an independent evaluator and the patient using intraclass correlation (ICC), and agreement on activity in individual joints by kappa statistics. We also performed longitudinal analyses to assess consistency of assessments over time. Finally, we investigated the concordance of joint counts of different assessors in patients with different levels of disease activity. RESULTS: The reliability of patient self-performed joint counts was high when compared to independent objective assessment (ICC; 95%confidence interval (CI)) for the assessment of swelling (0.32; 0.15 to 0.46) and tenderness (0.75; 0.66 to 0.81), with higher agreement for larger joints (kappa: 0.57 and 0.45, respectively) compared to smaller joints (metacarpo-phalangeal joint (MCPs): 0.31 and 0.45; and proximal interphalangeal joint (PIPs): 0.22 and 0.47, for swelling and tenderness, respectively).Patients in remission according to the Simplified Disease Activity Index (SDAI ≤ 3.3) showed better concordance of the joint counts (swollen joint count (SJC) ties 25/37, tender joint count (TJC) ties 26/37) compared to moderate/high disease activity states (SDAI > 11; MDA/HDA: SJC ties 9/72, TJC ties 21/72). Positive and negative predictive values regarding the presence of SDAI remission were reasonably good (0.86 and 0.95, respectively). A separate training session for patients did not improve the reliability of joint assessment. The results were consistent in the longitudinal analyses. CONCLUSIONS: Self-performed joint counts are particularly useful for monitoring in patients having attained remission, as these patients seem able to detect state of remission.
21373798 Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis: im 2011 Oct Though excellent clinical results have been reported for total joint arthroplasty (TJA) in rheumatoid arthritis (RA) patients, the longitudinal effects of TJA on pain, physical function, and health-related quality of life in RA patients remain unknown. This study aimed to assess changes in disease activity and health-related quality of life after TJA in patients with established RA. We analyzed the effect of total knee arthroplasty (TKA) and total hip arthroplasty (THA) on RA disease activity in an observational cohort of RA patients. Of the registered RA patients, 333 TKA and 77 THA patients were followed for 5 years after surgery. RA disease activity and health-related quality of life were measured using the Disease Activity Score 28 (DAS28) and a Japanese version of the Stanford health assessment questionnaire (J-HAQ). The mean DAS28 in TKA patients decreased from 4.66 (preoperatively) to 4.02 (3 years postoperatively) and to 3.94 (5 years postoperatively); the mean DAS28 in THA patients decreased from 4.41 (preoperatively) to 3.99 (3 years postoperatively) and to 3.92 (5 years postoperatively). The mean J-HAQ for TKA remained essentially unchanged, ranging from 1.48 (preoperatively) to 1.45 (3 years postoperatively) and to 1.47 (5 years postoperatively); the mean J-HAQ for THA also remained unchanged, ranging from 1.74 (preoperatively) to 1.74 (3 years postoperatively) and to 1.73 (5 years postoperatively). Of the total J-HAQ score, the lower limb score improved while the upper limb score worsened. Although TKA and THA improve clinical outcomes in damaged knees and hips and have a positive secondary systemic effect on RA disease activity, they have not had a continuously good effect on the measures of health-related quality of life. We conclude that tight control of RA disease activity is indicated for those patients with TKA and/or THA.
21203790 Predicting outcomes in rheumatoid arthritis. 2011 Mar Biologic therapies have brought improved efficacy in the field of rheumatoid arthritis (RA), but their use in clinical practice may be limited by concerns over cost. Predictive models are, therefore, needed to identify those people with RA with the worst potential outcomes, who will benefit most from the use of these drugs. A variety of studies have investigated factors that will predict the onset of RA to allow preventative intervention and the identification of prognostic factors to guide the need for aggressive treatment at the time of diagnosis and prognostic factors in patients who have failed on optimal traditional therapies-all strategies to guide the cost-effective use of modern therapies. Prediction rules have been developed that are sensitive and specific, but many are limited by their complexity or the need for biomarkers that will never be routinely measured in the clinic. Most rules to date have therefore failed to have a major impact on clinical practice. Probably most interesting is the prediction of response to therapy based upon early treatment response, with outcomes at as early as 3 months predicting response at 12 months. Further work is needed, however, to identify the efficacy of current therapies in preventing disease onset and the long-term cost-effectiveness of appropriately targeted treatment with biologics.
20851924 Rheumatoid arthritis-interstitial lung disease-associated mortality. 2011 Feb 1 RATIONALE: Mortality rates from rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are largely unknown. OBJECTIVES: We sought to determine mortality rates from rheumatoid arthritis-associated interstitial lung disease in the United States from 1988 through 2004. METHODS: Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with rheumatoid arthritis-associated interstitial lung disease, determined the prevalence of interstitial lung disease in all decedents with rheumatoid arthritis, and compared the age and underlying cause of death in these two cohorts of decedents. MEASUREMENTS AND MAIN RESULTS: From 1988 to 2004, there were 39,138,394 deaths in U.S. residents and 162,032 rheumatoid arthritis-associated deaths. Of these deaths, 10,725 (6.6%) met criteria for rheumatoid arthritis-associated interstitial lung. Mortality rates from rheumatoid arthritis fell over the course of this study in both women and men. However, mortality rates from rheumatoid arthritis-associated interstitial lung disease increased 28.3% in women (to 3.1 per million persons in 2004) and declined 12.5% in men (to 1.5 per million persons in 2004). Because the rate of decline in rheumatoid arthritis outpaced rheumatoid arthritis-associated interstitial lung disease in men, the prevalence of rheumatoid arthritis-associated interstitial lung disease increased in both sexes over time. CONCLUSIONS: Clinically significant RA-ILD occurs in nearly 10% of the RA population, and is associated with shortened survival and more severe underlying disease. Whereas overall mortality rates for RA have fallen, those associated with RA-ILD have increased significantly in older age groups.
23227612 [Monitoring of patients with rheumatoid arthritis]. 2012 Oct Monitoring of patients with rheumatoid arthritis must include the monitoring of the effectiveness of the treatments with a goal of remission or of low disease activity, the tolerance follow-up of the different treatments and the monitoring of cardiovascular risk factors. This follow-up is collaboration between the rheumatologist and the general practitioner for optimal outcomes.
22998573 T cell immunoglobulin-3 as a new therapeutic target for rheumatoid arthritis. 2012 Dec T cell immunoglobulin-3 (Tim-3) is a surface molecule expressed on various cell types of the immune system which plays a central role in immune regulation. Recently, identification of galectin-9 (Gal-9) as a ligand for Tim-3 has established the Tim-3-Gal-9 pathway as an important regulator of Th1 immunity and induction of tolerance. The interaction of Tim-3 with Gal-9 induces cell death; the in vivo blockade of this interaction results in exacerbated autoimmunity and abrogation of tolerance in experimental models, thus establishing Tim-3 as a negative regulatory molecule. A number of previous studies have demonstrated that Tim-3 influences chronic autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus. In addition, an association between Tim-3 polymorphisms and susceptibility to several autoimmune diseases has been identified in various autoimmune diseases, including rheumatoid arthritis (RA). Recent work has focused on the role of Tim-3 in RA, and the results indicate that Tim-3 may represent a novel target for the treatment of RA. In this article we will discuss the Tim-3 pathway and the therapeutic potential of modulating the Tim-3 pathway in RA.
21979316 [University contribution to implementation of the treat-to-target concept in rheumatology] 2011 Oct Following similar examples for diabetes mellitus and hypertension an attempt was made to establish a treat-to-target (T2T) program for rheumatic diseases in order to improve the course of the disease. Nevertheless, it is a factum that rheumatology, a recognized discipline in internal medicine, was not represented in university clinics corresponding to its scientific, clinical and socioeconomic importance. On the question how rheumatology in university clinics can contribute to the implementation of a T2T program, several aspects have to be considered. These include improvement in training and further education, establishment of clinical scientific core topics, formulation of guidelines, initiation of controlled studies, establishment of long-term cohorts and the incorporation of pathogenetic and therapeutic information in international networks and national symposia.
22337235 Time to consultation and disease-modifying antirheumatic drug treatment of patients with r 2012 Apr OBJECTIVE: To determine the timeliness of consultation and initiation of disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) referred to rheumatologists. METHODS: The first part of the study was a review of the charts of 151 patients with RA followed by 3 rheumatologists. The outcome measure was the interval between symptom onset and consultation with a rheumatologist. The second part of the study involved a chart review of 4 family physician practices in a small urban center in order to determine the accuracy of diagnostic coding (International Classification of Diseases; ICD-9) of RA, as well as the proportion of patients with RA seen by a rheumatologist. Finally, a survey was sent to primary care physicians at a group of walk-in clinics to determine what percentage of their patients with RA were referred to a rheumatologist and, concerning referral patterns, how likely it is they would refer a confirmed or suspected RA patient to a rheumatologist. RESULTS: Patients with RA referred to rheumatologists in this sample were seen by a rheumatologist at a mean of 9.8 months (median 5 mo, range 0-129 mo) after symptom onset, and mean 1.2 months (median 4.0 mo, range 0-8 mo) after being referred by their primary care physician. All referred patients with confirmed RA were started on DMARD within 1 week of initial consultation. Primary care physicians would refer suspected RA patients 99.5% of the time (median 100, range 90-100%), and 87.6% (median 90, range 50-100%) of patients with confirmed RA would have seen a rheumatologist at least once. A chart review showed that, in a select group of family physicians, 70.9% (22/31) of patients coded as RA per the ICD-9 did indeed have RA and all had seen a rheumatologist for their condition. CONCLUSION: In Northern Alberta, patients with RA are seen and started on DMARD therapy in a timely fashion. Most of the delay is at the primary care level, suggesting a need for improved education of patients and primary care physicians rather than a formal triage system.
22286359 [Rheumatoid arthritis and multiple myeloma as comorbidity. Is tocilizumab a therapy option 2012 Jan Multiple myeloma (MM) is a disease of the elderly with an incidence of 4/100,000 per year and can occur as a comorbidity especially in elderly patients with rheumatoid arthritis (RA). For MM and also for RA interleukin-6 (IL-6) is a pathogenetically important cytokine in both disease events. This article presents the case of a female patient who achieved sustained remission of RA and stabilization of MM with quantitative reduction of paraprotein by treatment with tocilizumab. The question whether tocilizumab represents a meaningful treatment approach for treatment of RA when MM is also present will be discussed.
21773825 Elevation of serum KL-6 levels in 3 patients with rheumatoid arthritis treated with adalim 2012 Feb We describe 3 cases of rheumatoid arthritis presenting with elevated serum KL-6 levels during treatment with adalimumab, which was discontinued because of suspected onset of complications. However, no complications were observed following discontinuation despite comprehensive assessments, and KL-6 levels subsequently returned to baseline levels. In our institutes, 3 out of 29 cases treated with adalimumab showed elevated KL-6 levels. The baseline levels were 445, 347, and 547 U/ml, while the peak levels were 1010, 546, and 2007 U/ml, respectively. The elevated KL-6 levels seem to have been innocuous; nevertheless, further careful observation is deemed necessary.