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ID PMID Title PublicationDate abstract
18378278 Prevalence and clinical relevance of autoimmune neutropenia in patients with primary Sjög 2009 Apr OBJECTIVE: To analyze the prevalence of neutropenia in a large cohort of patients with primary Sjögren's syndrome (SS) and its association with clinical and immunological disease expression and adverse outcomes. METHODS: The study cohort included 300 patients diagnosed with primary SS in our department between 1984 and 2002. The outcomes measured after the first laboratory evidence of neutropenia (<2.5 x 10(9)/L) were first hospital admission caused by infection, development of systemic manifestations, neoplasia, and death. RESULTS: Ninety-nine (33%) patients had neutropenia during the follow-up, which was related to neoplasia or drugs in 9 (3%) patients and was considered idiopathic in the remaining 90 (30%). Patients with neutropenia had a lower mean age at diagnosis of SS (51.9 versus 59.4 years, P < 0.001) and a higher prevalence of anti-Ro/La antibodies (53% versus 22%, P < 0.001), rheumatoid factor (49% versus 32%, P = 0.009), and low C4 levels (17% versus 8%, P = 0.044) than those without neutropenia. Patients with neutropenia had a higher incidence of hospital admission caused by infection (24% versus 9%, P = 0.002), especially those with neutropenia <1 x 10(9)/L (50% versus 9%, P = 0.002), and a higher rate of admission (log rank = 0.0023) in comparison with those without neutropenia. Agranulocytosis was found in 7 (2%) patients, predominantly related to neoplasia (5 cases). One (1%) of the 90 patients with SS-related neutropenia developed large granular lymphocyte T-cell leukemia. CONCLUSION: Neutropenia should be considered a relevant hematologic finding of primary SS, due both to its elevated prevalence and to its clinical significance (close association with anti-Ro/La antibodies, coexistence with other cytopenias, and development of severe infections).
20954341 [Pharmacoeconomics of molecular target drugs in Japan]. 2010 Oct Various molecular target drugs are developed in recent era in Japan, especially for treatment of cancer, rheumatoid arthritis and other diseases. Although they are much more effective compared to previous drugs, their costs are much more expensive. Thus, pharmacoeconomic analysis in which we evaluate their efficiency, would be highly needed. When we take pharmacoeconomic analyses, we need to assess both costs and health outcomes. In addition, we must compare cost-effectiveness of new interventions and control. To estimate costs of each intervention, not only direct medical costs, but direct non-medical costs (e.g. transportation costs, caregiving costs, house--modification costs) and indirect costs, or productivity losses should be separately calculated and presented. To evaluate efficiencies of anti-rheumatoid biologic agent in Japan, we started to collaborate with large-scale cohort of patient with rheumatoid arthritis in Japan, IORRA cohort in Tokyo Women's Medical University. With this data, we are taking various pharmacoeconomic analysis.
27789987 Recent advances in neutralizing the IL-6 pathway in arthritis. 2009 Recent advances in understanding the mechanism(s) of how IL-6 trans-signaling regulates immune cell function and promotes inflammation in autoimmune arthritis are critically reviewed. Serum and/or synovial fluid (SF) IL-6 is markedly elevated in adult and juvenile rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and osteoarthritis (OA). IL-6, in concert with IL-17, determines the fate of CD4(+) lymphocytes and therefore TH(17) cell differentiation. IL-6 also plays a critical role in modulating B-lymphocyte activity. The recognition that IL-6 trans-signaling regulates inflammation resulted in the development of tocilizumab, a fully humanized monoclonal antibody that neutralizes the biological activity of the IL-6-receptor (IL-6R). Significant clinical benefit was demonstrated as well as reduced serum IL-6 levels with suppression of X-ray progression of disease in several clinical trials in which juvenile or adult RA patients were treated with tocilizumab monotherapy or tocilizumab plus methotrexate. However, levels of serum and/or SF IL-6 cytokine protein superfamily members, adiponectin, oncostatin M, pre-B-cell colony enhancing factor/visfatin and leukemia inhibitory factor are also elevated in RA. Additional studies will be required to determine if anti-IL-6 trans-signaling inhibition strategies with tocilizumab or recombinant soluble IL-6R reduce the level of these cytokines.
20035333 The effects of PDL-Ig on collagen-induced arthritis. 2011 Apr Programmed death ligand (PDL) is a new member of the B7 family of costimulatory molecules that specifically interacts with programmed death 1 (PD-1) expressed on activated T cells, B cells, and myeloid cells. Collagen II (CII)-induced arthritis (CIA) is an experimental model of arthritis that has been used to dissect the pathogenesis of human rheumatoid arthritis. In this study, we have investigated the effects of PDL-Ig on CIA. Administration of PDL-Ig significantly ameliorated the disease as assessed by clinical arthritis score and histology in the joints. Expression of proinflammatory cytokines, such as IL-17 and IL-23, in the serum was reduced by PDL-Ig treatment. These results showed a beneficial effect of PDL-Ig on CIA through anti-inflammatory actions and inhibition of cell proliferation in response to CII, suggesting that the PD-1-PDL pathway may be involved in the pathogenesis of CIA, and thus PDL-Ig may be a useful therapy for the improvement of human rheumatoid arthritis.
19669855 Pulmonary arterial hypertension complicating adult-onset Still's disease. 2013 Mar Adult-onset Still's disease (AOSD) is a rare condition diagnosed by a combination of clinical and laboratory features and after ruling out other conditions. Pulmonary manifestations, apart from pleuritis, are uncommon and pulmonary arterial hypertension (PAH) in extremely uncommon. We have described a case of AOSD with severe PAH. There have been rare reports of PAH occurring in AOSD in the literature. Probably, this manifestation may have been understudied, being confined to cases which are symptomatic. A larger study to look at the asymptomatic occurrences of PAH in AOSD may help in unraveling the mystery of this disease.
20476895 Abatacept in the treatment of rheumatoid arthritis. 2009 Jan Rheumatoid arthritis (RA) is a chronic inflammatory arthritis affecting 1% of the population. The immunologic dysfunction underlying this immune disorder is complex and intricate with the involvement of various immune cells as well as cytokines and surface molecules. While inhibition of TNF-alpha has changed the outlook of patients with this disorder, it regulates only one aspect of the inflammatory cascade associated with RA. This is corroborated by experience in the clinic, where a significant proportion of the patients do not have clinical benefit with such therapies. Furthermore, a number of patients experience blunting of the initial therapeutic benefits of TNF-alpha-targeted therapies. Thus, a different approach to regulate the immune dysfunction associated with RA is necessary. T cells are considered important in the pathogenesis of RA and abatacept, a fusion protein, was developed to abolish the activation of the T cell by blocking its interaction with the antigen-presenting cell. Abatacept has demonstrated promising clinical improvements in patients with RA. Although clinical experience with this new drug is limited and its mechanism of action remains to be understood, the data on the safety profile are reassuring.
20347831 Rheumatoid factor interference in immunogenicity assays for human monoclonal antibody ther 2010 May 31 Rheumatoid factors (RFs) are endogenous human antibodies that bind to human gamma globulins. RFs demonstrate preferential binding to aggregated gamma globulins and are involved in the clearing mechanism of immune complexes. Immunoassays designed to measure human anti-human antibodies (HAHA) after administration of monoclonal antibody therapeutics are thus vulnerable to interference from RFs. When using a sensitive electrochemiluminescent (ECL) bridging immunoassay, samples from subjects with rheumatoid arthritis demonstrated much higher baseline reactivity than healthy subjects. Interference was found to be dependent on the aggregation state of the therapeutic antibody that had been conjugated with the detection reagent (ruthenium). Size exclusion high performance liquid chromatography (SE-HPLC) demonstrated that of the total integrated peaks, as little as 0.55% high molecular weight aggregates (>600kDa) were sufficient to cause increased reactivity. Stability studies of the ruthenium and biotin conjugated therapeutic antibody indicated that storage time, temperature and buffer formulation were critical in maintaining the integrity of the reagents. Through careful SE-HPLC monitoring we were able to choose appropriate storage and buffer conditions which led to a reduction in the false reactivity rate in therapeutic-naïve serum from a rheumatoid arthritis population.
21794592 [What are patients with early rheumatoid arthritis like in Spain? Description of the PROAR 2009 May OBJECTIVE: To identify factors present in recent onset arthritis that may help to predict rheumatoid arthritis (RA), and to describe a cohort of recent onset RA. PATIENTS AND METHOD: A 5 year prospective cohort of patients with early oligo and polyarthritis (< 1 year of evolution) from 34 rheumatology units, was studied. Sociodemographic, clinical features and RA risk factors were recorded. Rheumatoid factor (RF), anti-CCP determinations and radiographs of hands and feet were analyzed too. After three years, a diagnosis of certainty and the variables that determined the evolution to RA, were evaluated. RESULTS: One hundred and seventy one patients were included; 161 (94.2%) fulfilled RA diagnostic criteria; most of them (157; 97.5%) in the first visit. Factors associated with RA diagnosis were: positive RF, anti-CCP and DAS-28; 65% of the patients had radiological erosions in the first visit. CONCLUSIONS: Positive RF, anti-CCP and the disease activity are predictive factors of RA. Radiological damage exists very early in most of patients, that's why it is more important to treat the disease aggressively instead than achieving an RA diagnosis of certainty.
18304610 Assessing the impact of psoriatic arthritis on patient function and quality of life: lesso 2009 Feb OBJECTIVES: To identify and describe measures that can be used to assess the impact of psoriatic arthritis (PsA) on patient functioning and health-related quality of life (HRQOL). METHODS: A literature search of the PubMed database to identify papers describing assessment tools for quality of life and function in rheumatic diseases. RESULTS: Many tools have been developed that can be used to assess the impact of rheumatic disease on patient functioning and HRQOL. Although several disease-specific tools have been developed for rheumatoid arthritis, ankylosing spondylitis, and psoriasis, few have been developed specifically for PsA, a condition that affects both skin and joints. However, several have been adopted from their use in other conditions and used in clinical trials, such as the Health Assessment Questionnaire and Short Form 36 and have shown good performance characteristics. The Psoriatic Arthritis Quality of Life questionnaire, a recently developed disease-specific instrument, has good internal consistency, validity, and reliability. Initiatives are underway by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis to evaluate Psoriatic Arthritis Quality of Life responsiveness to treatment in clinical trials, in addition to other projects intended to improve the assessment of quality of life and function in PsA. These efforts are influenced by "lessons learned" from assessment tools in rheumatoid arthritis, ankylosing spondylitis, and psoriasis. CONCLUSIONS: Assessing the impact of PsA and its treatment on patient function and quality of life is critical to improving patient outcomes, and therefore, valid and reliable tools that can be easily used in both clinical trials and clinical practice are being developed and refined.
21253624 [A short history of anti-rheumatic therapy. IV. Corticosteroids]. 2010 Oct In 1948 a corticosteroid compound was administered for the first time to a patient affected by rheumatoid arthritis by Philip Showalter Hench, a rheumatologist at the Mayo Clinic in Rochester, Minnesota (USA). He was investigating since 1929 the role of adrenal gland-derived substances in rheumatoid arthritis. For the discovery of cortisone and its applications in anti-rheumatic therapy, Hench, along with Edward Calvin Kendall and Tadeusz Reichstein, won the 1950 Nobel Prize for Medicine. In this review we summarize the main stages that led to the identification of the so-called compound E, which was used by Hench. We also consider the subsequent development of steroid therapy in rheumatic diseases, through the introduction of new molecules with less mineralocorticoid effects, such as prednisone, and more recently, deflazacort.
21794692 [Does early treatment of Rheumatoid Arthritis lead to a better long-term prognosis?]. 2010 Mar Time is a crucial dimension in most chronic diseases, especially in inflammatory rheumatic disease, which it affects in many ways. Early treatment in rheumatoid arthritis (RA) is an essential issue, as joint damage occurs within the first weeks or months of the disease process and inflammatory activity maintained over time is responsible for all of the consequences of the disease. The introduction of new drugs with faster and more effective action, such as tumor necrosis factor (TNF) inhibitors, has represented a major shift in the strategy of RA treatment, allowing the clinician to aim for remission and prevention of structural damage as realizable goals.
22291497 Rituximab in severe skin diseases: target, disease, and dose. 2010 New clinical indications for rituximab seem to appear every day. This review will trace the use of this monoclonal antibody from lymphoid malignancy, to classic autoimmune disease, and specifically severe autoimmune skin diseases. The history leading to different dosing schema with associated pharmacokinetic data will be discussed. A case of livedoid vasculopathy (atrophie blanche) responding to rituximab will illustrate how the response to therapy can help to elucidate previously obscure pathophysiology.
19562236 Common prognostic factors of work disability among employees with a chronic somatic diseas 2009 Jul OBJECTIVE: Based on prospective and retrospective disease cohort studies, the aim of this review was to determine common prognostic factors for work disability among employees with rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, diabetes mellitus, and ischemic heart disease (IHD). METHODS: A systematic literature search in Medline (1990-2008) and Embase (1990-2008) was carried out to identify relevant cohort studies using a well-defined list of inclusion and quality criteria. RESULTS: We identified 43 relevant cohort studies with sufficient methodological quality (20 for rheumatoid arthritis, 3 for asthma and 20 for IHD). The common prognostic factors for work disability found in all the diseases were: perceived health complaints, limitation in daily physical activities caused by the disease (high versus low), heavy manual work, and female gender. The common positive prognostic factors for rheumatoid arthritis and IHD were age (high versus low) and sickness absence. The common negative factors for rheumatoid arthritis and IHD were education (high versus low) and ethnic origin (white versus non-white). CONCLUSIONS: As many prognostic factors for work disability are similar for employees with various chronic diseases, it is possible to detect high risk groups. This information supports the development and implementation of a general disability management intervention for employees suffering from a chronic disease to overcome health-related limitations at work.
21794637 [Are imaging techniques necessary for defining remission in rheumatoid arthritis?]. 2009 Apr Accurate assessment of inflammatory activity in rheumatoid arthritis (RA) is essential to evaluate response to therapy and disease remission. RA remission has been classically assessed by clinical and laboratory parameters. However, subclinical synovitis may explain progression of joint damage in spite of apparent clinical remission in RA patients. Imaging techniques, such as magnetic resonance imaging and high-resolution ultrasonography (US) with Doppler technique, provide a sensitive measure and monitoring of joint inflammatory activity and a more accurate assessment of RA remission than clinical evaluation which may contribute to make optimal treatment decisions. Within the last decade, an increasing number of rheumatologists have progressively incorporated musculoskeletal US as a valuable diagnostic tool in their clinical practice. This technique facilitates the scanning of all peripheral joints as many times as required at the time of consultation.
20018061 Identification of correlated genetic variants jointly associated with rheumatoid arthritis 2009 Dec 15 Using the North American Rheumatoid Arthritis Consortium genome-wide association dataset, we applied ridged, multiple least-squares regression to identify genetic variants with apparent unique contributions to variation of anti-cyclic citrullinated peptide (anti-CCP), a newly identified clinical risk factor for development of rheumatoid arthritis. Within a 2.7-Mbp region on chromosome 6 around the well studied HLA-DRB1 locus, ridge regression identified a single-nucleotide polymorphism that was associated with anti-CCP variation when including the additive effects of other single-nucleotide polymorphisms in a multivariable analysis, but that showed only a weak direct association with anti-CCP. This suggests that multivariable methods can be used to identify potentially relevant genetic variants in regions of interest that would be difficult to detect based on direct associations.
20018024 On the association between rheumatoid arthritis and classical HLA class I and class II all 2009 Dec 15 Using single-nucleotide polymorphisms (SNPs), we sought to predict classical class I and class II human leukocyte antigen (HLA) alleles, and test for their associations with rheumatoid arthritis (RA) in the North American Rheumatoid Arthritis Consortium sample of cases and controls, genotyped on the Illumina HumanHap550 BeadChip. We use publicly available databases of SNP data and HLA data to find SNPs or SNP-haplotypes to be used as surrogates for each HLA allele. To reduce the confounding effects of linkage disequilibrium with the HLA-DRB1 locus, we tested for the association conditional on the presence or absence of a shared epitope allele on the same haplotype as the target HLA allele. Using SNP surrogates, we find that components of the DQ8 serotype (DQA1*0301:DQB1*0302) are associated with RA, irrespective of the presence or absence of a shared epitope allele on their respective haplotypes. Knowledge of the haplotype structure in the HLA region is still necessary for better interpretation of the results.
20581017 Cardiovascular risk factors in primary Sjögren's syndrome: a case-control study in 624 pa 2010 Jul We evaluated the prevalence and clinical significance of cardiovascular risk factors in a large series of patients with primary Sjögren's syndrome (SS), focusing on the possible association with clinical and immunological SS features, the therapies administered, and the impact on cardiovascular disease. The study cohort included 312 patients fulfilling the 2002 classification criteria for primary SS, consecutively evaluated and followed in our department between 1984 and 2009. The control group consisted of 312 age- and sex-matched patients without systemic autoimmune diseases followed during the study period in a primary care centre. In comparison with the age- and sex-matched control group, patients with primary SS showed a higher frequency of diabetes mellitus (27% versus 13%, p < 0.001) and hypertriglyceridaemia (22% versus 15%, p = 0.023), and a lower frequency of hypertension (30% versus 46%, p < 0.001) and smoking (19% versus 31%, p < 0.001). The adjusted, multivariate analysis showed that SS patients with at least three cardiovascular risk factors had a higher mean age at SS diagnosis (p < 0.001), a higher frequency of liver involvement (p = 0.01) and central nervous system involvement (p = 0.001), higher mean levels of C-reactive protein (CRP, p = 0.001), a lower percentage of circulating gamma globulins (p = 0.001), and had received corticosteroids more frequently (p = 0.003) in comparison with patients without cardiovascular risk factors. Patients who had received corticosteroids showed a higher frequency of hypertension (37% versus 25%, p = 0.032), diabetes mellitus (37% versus 21%, p = 0.002), and hypertriglyceridaemia (33% versus 15%, p < 0.001). Patients with primary SS showed a twofold higher prevalence of diabetes mellitus and a 1.5-fold higher prevalence of hypertriglyceridaemia in comparison with primary care patients. Corticosteroid use was closely associated with cardiovascular risk factors. These results suggest that cardiovascular risk factors should be taken into account in the management of patients with primary SS and show the importance of recognizing and controlling both traditional and SS-related modifiable risk factors.
19727217 [Clinical features of primary Sjogren syndrome in youth]. 2009 Jun 18 OBJECTIVE: To observe the clinical features of primary Sjogren syndrome (pSS) in young people (< or =34 years). METHODS: The data of 232 patients with pSS who were in hospital from 2004 to 2008 were analysed in a prospective study. RESULTS: A total of 23.7%(55/232) patients' symptoms came on in youth (< or =34 years), who were all females, mean age was (27.6+/-6.2) years. The other 177 patients' symptoms came on when they were more than 34 years old. In young group, 32.73%(18/55) patients' first symptoms were xerostomia and/or keratoconjunctivitis sicca, the other 67.27%(37/55)came on without xerostomia and keratoconjunctivitis sicca, while in the middle-aged and aged group, 59.32%(105/177) patients' first symptoms were xerostomia and/or keratoconjunctivitis sicca, 40.67% (72/177)without xerostomia and keratoconjunctivitis sicca. There was significant difference(P=0.001). The duration from first symptom to first diagnosis of pSS in the young group was (93+/-107) months, which was significantly longer than those of the middle-aged and aged group [(45+/-59) months, P=0.001]. The systemic damage of the young group was 61.8%(34/55), which was significantly greater than 41.24%(73/177)in the middle-aged and aged group(P=0.026). CONCLUSION: Primary Sjogren syndrome in young people is not rare, and about 2/3 of them come on without xerostomia and/or keratoconjunctivitis sicca. Not only the duration from first symptom to first diagnosis of pSS in the young group is longer, but also the systemic damage of the young group is greater than those of the middle-aged and aged group. These findings should alert the clinician to make the possible diagnosis of pSS in young patients.
20075703 Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features and long- 2010 Jan Reactive hemophagocytic syndrome (RHS) is a rare, life-threatening, and little-known complication of rheumatic diseases. This disorder is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms. RHS may develop in patents who have lymphoma, organ transplantation, serious infection, and rheumatic diseases, most notably systemic lupus erythematosus and adult-onset Still disease (AOSD). Observations of specific cases of RHS in AOSD remain rare, and the significance of this syndrome during the course of AOSD remains unknown. We retrospectively studied 16 episodes of AOSD-associated RHS in 8 patients. To determine whether RHS is associated with a particular phenotype of AOSD, we conducted a case-control study from the cohort of AOSD patients seen during the same period. The estimated frequency of RHS in AOSD patients from our cohort was 15.3% (8/52). The median age at RHS diagnosis was 44.5 years. We collected clinical and laboratory data. RHS was the first manifestation of AOSD in 7 cases. The main symptoms were fever (n = 8), salmon rash (n = 6), arthralgia (n = 7), lymphadenopathy (n = 6), and shock (n = 4). Serum ferritin concentration was consistently elevated (>1000 microg/L in 8 cases), and the level of glycosylated ferritin was low in all cases (<5% in 7 cases, 15% in 1 case). Six patients presented with coagulopathy; hypertriglyceridemia was found in 6 cases. Admission to the intensive care unit was required in 4 cases. Treatment included corticosteroids (n = 8) and intravenous immunoglobulin (n = 6), cyclophosphamide in 2 cases, infliximab in the same 2 cases, and cyclosporine in 1 case. With a follow-up ranging from 2 to 15 years, the patients were in remission with prednisone plus methotrexate (n = 4), prednisone plus infliximab (n = 2), and low-dose prednisone alone (n = 2). We compared the 8 patients included in this study with 44 control patients with AOSD without RHS. Low haptoglobin levels, very high ferritin levels (>10,000 microg/L), and a normal or low neutrophil count seem to be predictive factors of the occurrence of RHS in AOSD.
29320019 2010 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation of the joints. The disease affects 0.5% to 1% of the adult population, and causes severe pain and disability. Direct costs related to treatment, and indirect costs associated with occupational disability, is significant. RA is treated with an interdisciplinary approach, in which disease modifying anti-rheumatic drugs (DMARDs) are an important component. The recommended first choice is one or more DMARDs. In the absence of treatment effect, a biologic drug may be added. The purpose of this systematic review was to investigate the efficacy and safety of biologics, compared with DMARDs in patients with early (≤ 3 years) RA. The commisioner is the Norwegian Rheumatism Association, whose members are concerned with good treatment at the early stages of RA. We included a total of 12 randomised controlled trials that examined the effect of biologics infliximab, adalimumab, etanercept and abatacept. The results suggest that, compared with DMARDs alone, biologicals in combination with DMARDs give: more patients in remission; neither more or less serious adverse events; more patients who achieved a 50% improvement; improved physical function; less joint destruction. Due to methodological weaknesses in the included studies most results contain some degree of uncertainty.