Browse

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

ID PMID Title PublicationDate abstract
25936426 Tuberculous pyomyositis in a rheumatoid arthritis patient treated with anakinra. 2015 Sep Musculoskeletal tuberculosis (TB) occurs in only 3% of patients with TB while tuberculous pyomyositis is rare. It usually affects immunocompromised or patients with underlying comorbidities. We present a case of tuberculous pyomyositis in a 85-year-old Caucasian patient with rheumatoid arthritis (RA) treated with steroids and anakinra. The patient presented with fever as well as redness, swelling and induration on the lateral side of the hip and thigh. Under ultrasound guidance fluid collection of the thigh was aspirated. Polymerase chain reaction (PCR) and cultures of the fluid were positive for Mycobacterium TB. The patient underwent bronchoscopy. PCR and cultures from the bronchoalveolar lavage were also positive for Mycobacterium TB. The patient was treated with anti TB treatment with amelioration of the inflammation in the hip and thigh. This is the first reported case of tuberculous pyomyositis in a RA patient treated with anakinra.
26353369 Registration-Based Morphometry for Shape Analysis of the Bones of the Human Wrist. 2016 Feb We present a method that quantifies point-wise changes in surface morphology of the bones of the human wrist. The proposed method, referred to as Registration-based Bone Morphometry (RBM), consists of two steps: an atlas selection step and an atlas warping step. The atlas for individual wrist bones was selected based on the shortest â„“2 distance to the ensemble of wrist bones from a database of a healthy population of subjects. The selected atlas was then warped to the corresponding bones of individuals in the population using a non-linear registration method based on regularized â„“2 distance minimization. The displacement field thus calculated showed local differences in bone shape that then were used for the analysis of group differences. Our results indicate that RBM has potential to provide a standardized approach to shape analysis of bones of the human wrist. We demonstrate the performance of RBM for examining group differences in wrist bone shapes based on sex and between those of the right and left wrists in healthy individuals. We also present data to show the application of RBM for tracking bone erosion status in rheumatoid arthritis.
27586802 Targeting GM-CSF in rheumatoid arthritis. 2016 Jul Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well-known as a haemopoietic growth factor. However, it is also essential in regulating functions of mature myeloid cells such as macrophages. Preclinical studies and observations of flares of arthritis in patients following GM-CSF treatment supported its important contribution to the pathogenesis of rheumatoid arthritis (RA). As the most advanced compound, mavrilimumab, a monoclonal antibody against GM-CSF receptor, has already completed phase II trials with a long term of follow-up period of 74 weeks. During this exposure period, an acceptable sustained safety and tolerability profile has been observed addressing the concerns of development of cytopenias or pulmonary alveolar proteinosis. Of note, a rapid and sustained efficacy and normalisation of acute phase reactants were consistently shown in studies both targeting GM-CSF and its receptor. Its tumour necrosis factor (TNF) independent mode of action with concurrent blockade of GM-CSF as well as IL-17 signalling reported from preclinical studies supports the assumption that it can be a useful biologic and an alternative agent in TNF inhibitor resistant patients with RA. Therefore, subsequent studies are warranted to investigate the safety and efficacy of GM-CSF blocking agents in different subgroups of RA.
27906035 Extracellular vesicles in the pathogenesis of rheumatoid arthritis and osteoarthritis. 2016 Dec 1 Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity in the US population. Extracellular vesicles (EVs), including exosomes and microvesicles, are now recognized to play important roles in cell-to-cell communication by transporting various proteins, microRNAs (miRNAs), and mRNAs. EV-derived proteins and miRNAs impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of both OA and RA. Some of the processes by which these membrane-bound vesicles can alter joint tissue include extracellular matrix degradation, cell-to-cell communication, modulation of inflammation, angiogenesis, and antigen presentation. For example, EVs from IL-1β-stimulated fibroblast-like synoviocytes have been shown to induce osteoarthritic changes in chondrocytes. RA models have shown that EVs stimulated with inflammatory cytokines are capable of inducing apoptosis resistance in T cells, presenting antigen to T cells, and causing extracellular damage with matrix-degrading enzymes. EVs derived from rheumatoid models have also been shown to induce secretion of COX-2 and stimulate angiogenesis. Additionally, there is evidence that synovium-derived EVs may be promising biomarkers of disease in both OA and RA. The characterization of EVs in the joint space has also opened up the possibility for delivery of small molecules. This article reviews current knowledge on the role of EVs in both RA and OA, and their potential role as therapeutic targets for modulation of these debilitating diseases.
26463094 Is localized autoimmunity the trigger for rheumatoid arthritis? Unravelling new targets fo 2015 Sep The systemic autoantibodies that characterize rheumatoid arthritis (RA) are detectable well before patients develop disease and may originate from sites distant to the synovial joints. There is growing evidence that local autoimmune processes occur at mucosal sites in the earliest phases of RA, as well as in predisposed individuals who have not yet progressed to clinical disease. Mucosal autoimmunity has been described at the oral mucosa, lung, and gut in these subjects, and it is conceivable that different sites may provide the primary trigger for systemic autoimmunity in different individuals. At the oral mucosa and lung, risk factors such as periodontal disease and smoking may contribute to autoimmunity by driving the local generation of citrullinated autoantigens. A break in immune tolerance could lead to localized and then systemic autoimmunity, a hypothesis compatible with an etiological model for anti-citrullinated protein antibody (ACPA) positive RA. At the gut mucosa, the composition of the intestinal microbiome is central to local immune regulation. Here, there is evidence from animal models that alteration of the local microbiome can influence the balance of pro- and anti-inflammatory T cells and promote the development of autoimmune disease. In this review, we discuss the evidence for localized mucosal autoimmunity in those with preclinical and early RA. Autoimmunity at the oral mucosa, lung, and gut will be considered as potential initiating sites of RA-related autoimmunity.
25979945 The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment o 2016 Jun OBJECTIVE: To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA). METHODS: Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)). RESULTS: 666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (-0.38 (95% CI -0.64 to -0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75). CONCLUSIONS: Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.
26233505 Utility of Select Plasma MicroRNA for Disease and Cardiovascular Risk Assessment in Patien 2015 Oct OBJECTIVE: MicroRNA (miRNA) are small noncoding RNA that posttranscriptionally regulate gene expression and serve as potential mediators and markers of disease. Recently, plasma miR-24-3p and miR-125a-5p concentrations were shown to be elevated in rheumatoid arthritis (RA) and useful for RA diagnosis. We assessed the utility of 7 candidate plasma miRNA, selected for biological relevance, for RA diagnosis and use as markers of disease activity and subclinical atherosclerosis in RA. METHODS: The cross-sectional study included 168 patients with RA and 91 control subjects of similar age, race, and sex. Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were measured by quantitative PCR. Utility of plasma miRNA concentrations for RA diagnosis was assessed by area under the receiver-operating characteristic curve (AUROC). Associations between plasma miRNA concentrations and RA disease activity and coronary artery calcium score were assessed by Spearman correlations. RESULTS: Plasma concentrations of miR-15a-5p, miR-24-3p, miR-26a-5p, miR-125a-5p, miR-146a-5p, miR-155-5p, and miR-223-3p were significantly increased in patients with RA. The highest AUROC for diagnosis of RA (AUROC = 0.725) was found in miR-24-3p, including among rheumatoid factor-negative patients (AUROC = 0.772). Among all patients with RA, the combination of miR-24-3p, miR-26a-5p, and miR-125a-5p improved the model modestly (AUROC = 0.747). One miRNA, miR-155-5p, was weakly inversely associated with swollen joint count (p = 0.024), but no other miRNA were associated with disease activity or coronary artery calcium score. CONCLUSION: The combination of miR-24-3p, miR-26a-5p, and miR-125a-5p had the strongest diagnostic accuracy for RA. Candidate miRNA had little or no association with RA disease activity or subclinical atherosclerosis.
25535750 Diabetes mellitus risk factors in rheumatoid arthritis: a systematic review and meta-analy 2015 Jan OBJECTIVES: The aim of this study was to investigate the relationship between rheumatoid arthritis (RA) and the occurrence of diabetes mellitus (DM). METHODS: A meta-analysis was conducted to explore the risk of DM in RA patients. All relevant studies were identified by searching PUBMED, EMBASE and MEDLINE database prior to 1 January 2014. Pooled risk estimates were calculated with random-effects models using STATA 11.0. RESULTS: A total of 11 case-control studies and 8 cohort studies were included in the final analysis. The pooled risk estimate of 11 case-control studies showed a statistically significant increased risk of DM prevalence among RA individuals (OR=1.40, 95% CI: 1.34-1.47). The pooled risk estimate of 8 cohort studies also showed a statistically significant increasing risk of DM (RR=1.43, 95%CI: 1.38-1.47). In a subgroup analysis for case-control studies, the pooled risk estimate of individuals with RA increased the incidence of T1DM (type 1 diabetes mellitus) and the incidence of T2DM (type 2 diabetes mellitus) (OR, 4.78 vs. 1.41). In a subgroup analysis for cohort studies, RA was also found to have a statistically significant increasing risk of T2DM (RR=1.24, 95%CI: 1.14-1.35). Begg funnel plot and Egger test showed no evidence of publication bias. CONCLUSIONS: RA is associated with increased risk of DM, including T1DM and T2DM.
25917892 Leucine-rich α2 -glycoprotein as a potential biomarker for joint inflammation during anti 2015 May OBJECTIVE: To investigate whether leucine-rich α2 -glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA). METHODS: In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody. RESULTS: Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP. CONCLUSION: Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.
26542940 Semaphorin 4A as novel regulator and promising therapeutic target in rheumatoid arthritis. 2015 Nov 6 Rheumatoid arthritis (RA) is a systemic autoimmune disease manifesting in joint destruction. The recognized hallmark of RA pathogenesis is the involvement of immune cells which produce many mediators potentiating an inflammatory environment. RA synovial fibroblasts (RASFs) contribute significantly to disease progression by initiating and regulating many pathways of joint destruction. Detailed molecular insights into RASF biology may lead to identification of important therapeutic targets. The discovery of common molecular targets for joint resident and inflammatory cells may help to develop the most effective therapeutic strategy. One such pathway includes semaphorin 4A as reported in a recent article in Arthritis Research & Therapy.
25865479 Computer-based measurements of joint space analysis using metacarpal morphometry in hand r 2017 Sep AIM AND OBJECTIVES: The aim and objectives are as follows: (i) to perform an automated segmentation of the hand from radiographs using a dual tree complex wavelet-based watershed algorithm; ii) to compare the measured statistical features of the joint space of the hand using gray level co-occurrence matrix (GLCM) method with standard diagnostic parameters of rheumatoid arthritis (RA). METHODS: Fifty-three patients with RA and 17 age- and sex-matched healthy controls were included in the study. The erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, health assessment questionnaire score (HAQ), disease activity score (DAS) and hand radiographs of all the subjects were obtained. Joint space width and cortical thickness were measured in metacarpophalangeal joints (MCP) and metacarpal bone semi-automatically using MIMICS software. Dual tree complex wavelet transform-based watershed algorithm was applied for automated segmentation, and feature extraction was performed using the GLCM method in hand radiographs of the total population. RESULTS: In the RA group (n = 53), the joint space width measured in the MCP1, MCP3, MCP5 of the hand were reduced significantly (P < 0.01) by 16.4%, 15.6%, and 17.5%, respectively compared to the normal group (n = 17). The measured combined cortical thickness at the second, third and fourth metacarpal bones of the hand were reduced significantly (P < 0.01) by 9.5%, 12% and 8%, respectively in the RA group compared to the normal group. CONCLUSION: The dual tree complex wavelet transform-based watershed algorithm provided effective segmentation in the digitized hand radiographs. The standard diagnostic parameters for RA were highly correlated with measured statistical features at MCP3 hand joint in the total population studied.
27987492 [Significance and diagnostic value of synovial fluid anti-cyclic citrullinated peptide ant 2016 Dec 18 OBJECTIVE: To explore the significance of synovial fluid (SF) anti-cyclic citrullinated peptide (CCP) antibodies and anti-mutated citrullinated vimentin (MCV) antibodies in the diagnosis of serum negative rheumatoid arthritis (SNRA). METHODS: Enzyme linked immunosorbent assay (ELISA) method was apllied in the detection of two groups of patients with knee joint fluid resistance against CCP antibody and antibody of MCV, the experimental group to SNRA patients, a total of 29 cases, and the control for patients with osteoarthritis (OA), a total of 28 cases, and clinical manifestations and laboratory parameters of the two groups were collected. RESULTS: The positive rate of synovial fluid anti-CCP was 34.5% in the SNRA patients, which was significantly higher than 10.7% in the control patients(χ(2)=4.571, P<0.05). The positive rate of synovial fluid anti-MCV was 20.7% in the SNRA patients, which was significantly higher than 7.1% in the control patients(χ(2)=2.167, P>0.05). The SNRA patients of SF anti-CCP and anti-MCV positive had no significant difference from the SNRA patients of SF anti-CCP and anti-MCV negative in age, course and morning stiffness. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein(CRP) and DAS28 scores in the SF anti-CCP positive patients were higher than those of the SF anti-CCP negative patients. The levels of ESR, CRP and DAS28 scores in the SF anti-MCV positive patients were higher than those of the SF anti-MCV negative patients, (all P<0.01). SF anti-CCP had correlation with ESR, CRP(r=0.567, P<0.01; r=0.664, P<0.01). SF anti-MCV had correlation with ESR, CRP (r=0.344, P<0.01; r=0.749, P<0.01). CONCLUSION: SF anti-CCP and anti-MCV are helpful for the diagnosis of SNRA and judgement of SNRA activity.
27832086 Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remi 2016 OBJECTIVE: Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. METHODS: Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. RESULTS: The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. CONCLUSION: The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.
26373561 Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Corr 2015 Nov OBJECTIVE: Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. METHODS: A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 ± 13 yrs) from our outpatient clinic and in 77 age- and sex-matched controls. RESULTS: The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score ≥ 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs -19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. CONCLUSION: Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies.
27424016 Secondary Sjogren's Syndrome in 83 Patients With Rheumatoid Arthritis. 2016 Jul Sjogren syndrome (SS) can occur alone, primary Sjogren syndrome, or in association with other rheumatic diseases, secondary Sjogren syndrome (sSS), such as Rheumatoid arthritis (RA). The occurrence of Sjogren syndrome with RA makes it course worse and increases high morbidity and mortality of RA. In this exploratory study we aim to determine the prevalence of sSS (diagnosed based on the revised version of American-European consensus Group Classification Criteria: AUCG-criteria), sicca symptoms (dry eye, dry mouth), positive autoantibody tests (Anti RO or Anti-LA antibodies), UWSFR (Unstimulated Whole Salivary Flow Rate), Schirmer and Lissamine test. In this cross-sectional study, eighty three consecutive RA patients (according to American College of Rheumatology criteria 1987) who were visited at rheumatology clinic of Razi General Hospital located in the north of Iran entered into our study. Our exclusion criteria was a positive history of past head and neck radiation treatment, Hepatitis C infection, acquired immunodeficiency disease (AIDS), pre-existing lymphoma, sarcoidosis, graft versus host disease, use of anticholinergic drugs (including neuroleptics, antidepressants, antihypertensive and parasympatholytics). They examined with UWSFR by a rheumatologist and with Schirmer test and Lissamine test by an ophthalmologist. Participants were 90.4% female with the mean age 48.3±13 years. Duration of RA was in 36.1% less than 5 years, in 22.9% 5-10 years, in 12.1% 11-15 years and in 28.9% more than 15 years. Our results demonstrated that the prevalence of sSS was 5.9% (CI:0.6%-10.5%). Number of 27.7% of RA patients positively responded to at least one question about sicca symptoms. Among objective tests, only Positive UWSFR and Lissamine test were significantly more common in RA patients with sSS in comparison to ones without sSS (P<0.001, P=0.01 respectively). In RA patients, we found a linear trend between sicca symptoms and aging (P=0.02). In patients with sicca symptoms, among tests that used for assessing decrease in saliva or tear production, only USWFR significantly more common (P=0.01). IN CONCLUSION: In RA population in North of Iran prevalence of sSS was less than 10%. In them, a significant linear trend existed between aging and sicca symptoms. Among objective tests of AUCG-criteria (except for lip biopsy that was not performed in the current study) only UWSFR and Lissamine test were significantly more common in patients with sSS in comparison ones without it.
25616773 [Plasma cells]. 2015 Feb Plasma cells are specialized terminally differentiated B cells that synthesize and secrete antibodies to maintain humoral immunity. By the production of pathogenic antibodies, plasma cells contribute to the development of many conditions, such as autoimmune disorders, transplant rejection and allergies. Two different plasma cell compartments can independently generate different types of pathogenic antibodies: (1) short-lived plasmablasts (proliferating precursors of mature plasma cells) and plasma cells, which live only as long as B cells are activated. Consequently, these cells cause disease flares that respond to immunosuppressive drugs and B cell targeting therapies. (2) Long-lived non-proliferating memory plasma cells, which survive in niches in bone marrow and inflamed tissues for months, years or a lifetime independent of B or T cell help or antigen contact. Because they do not respond to immunosuppressants or treatment targeting B cells, they are responsible for refractory chronic conditions. Therefore, long-lived memory plasma cells in particular have emerged as important therapeutic targets and strategies to target these cells are discussed in this article. So far long-lived plasma cells can only be depleted by immunoablative therapy with antithymocyte globulin in the setting of stem cell transplantation or by treatment with proteasome inhibitors approved for multiple myeloma. These strategies provide options for treating refractory autoantibody-mediated diseases. One interesting approach aims at an antigen-specific elimination of target plasma cells without depleting the protective plasma cells responsible for maintaining humoral immunity.
26034155 Evaluation of Minimally Invasive, Ultrasound-guided Synovial Biopsy Techniques by the OMER 2016 Jan OBJECTIVE: Because limited data currently support the clinical utility of peripherally expressed biomarkers in guiding treatment decisions for patients with rheumatoid arthritis, the search has turned to the disease tissue. The strategic aim of the Outcome Measures in Rheumatology (OMERACT) synovitis working group over the years has been to develop novel diagnostic and prognostic synovial biomarkers. A critical step in this process is to refine and validate minimally invasive, technically simple, robust techniques to sample synovial tissue, for use both in clinical trials and routine clinical practice. The objective of the synovitis working group (SWG) at OMERACT 12 (2014) was to examine whether recently developed ultrasound (US)-guided synovial biopsy techniques could be validated according to the OMERACT filter for future clinical use recommendation. METHODS: The SWG examined whether current data reporting US-guided synovial biopsy of both large and small joints addressed the OMERACT filters of truth, discrimination, and feasibility. RESULTS: There are currently limited data examining the performance of US-guided synovial biopsy, mainly from observational studies. Thus, it remains critical to evaluate its performance, within the clinical trials context, against the current gold standard of arthroscopic biopsy, with particular reference to: (1) synovial tissue yield, (2) capacity to determine treatment response as measured by a validated synovial biomarker, and (3) tolerability of the procedure. CONCLUSION: We summarize the discrete work packages agreed to as requirements to validate US-guided synovial biopsy and therefore lead to a global consensus on the use of synovial biopsy for research and clinical practice.
28028155 Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undiffere 2017 Jan OBJECTIVES: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS). METHODS: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months). RESULTS: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively. CONCLUSION: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.
26986247 How compelling are the data for Epstein-Barr virus being a trigger for systemic lupus and 2016 Jul PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development. RECENT FINDINGS: SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression. These comprise impaired functions of EBV-specific T-cells with an inverse correlation to disease activity and elevated serum levels of antibodies against lytic cycle EBV antigens. The presence of EBV proteins in renal tissue from SLE patients with nephritis suggests direct involvement of EBV in SLE development. As expected for patients with immunodeficiencies, studies reveal that SLE patients show dysfunctional responses to other viruses as well. An association with EBV infection has also been demonstrated for other autoimmune diseases, including Sjögren's syndrome, rheumatoid arthritis, and multiple sclerosis. SUMMARY: Collectively, the interplay between an impaired immune system and the cumulative effects of EBV and other viruses results in frequent reactivation of EBV and enhanced cell death, causing development of SLE and concomitant autoreactivities.
27722215 JAK inhibitors: A broadening approach in rheumatoid arthritis. 2016 Aug Pfizer's Xeljanz (tofacitinib citrate) was the first Janus kinase (JAK) inhibitor to reach the market for rheumatoid arthritis (RA) following its U.S. approval in November 2012, and it has since gained approval in more than 45 countries as a second-line therapy for RA after failure of disease-modifying antirheumatic drugs (DMARDs). This emerging category has heralded an attractive new class of oral treatment options in RA, with a notable opportunity in patients who stop responding to DMARDs, but they are facing a challenging market. Despite RA affecting approximately 23.7 million people worldwide, Xeljanz faces a market dominated by the anti-tumor necrosis factor (anti-TNF) biologicals, which have robust long-term safety and efficacy. The availability of biosimilars of these market leaders is also intensifying competition, and a high price and uncertainty over long-term safety is currently tempering the market for the JAK inhibitors.