Browse

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

ID PMID Title PublicationDate abstract
22767531 The anti-inflammatory fungal compound (S)-curvularin reduces proinflammatory gene expressi 2012 Oct In previous studies, we identified the fungal macrocyclic lactone (S)-curvularin (SC) as an anti-inflammatory agent using a screening system detecting inhibitors of the Janus kinase/signal transducer and activator of transcription pathway. The objective of the present study was to investigate whether SC is able to decrease proinflammatory gene expression in an in vivo model of a chronic inflammatory disease. Therefore, the effects of SC and dexamethasone were compared in the model of collagen-induced arthritis (CIA) in mice. Total genomic microarray analyses were performed to identify SC target genes. In addition, in human C28/I2 chondrocytes and MonoMac6 monocytes, the effect of SC on proinflammatory gene expression was tested at the mRNA and protein level. In the CIA model, SC markedly reduced the expression of a number of proinflammatory cytokines and chemokines involved in the pathogenesis of CIA as well as human rheumatoid arthritis (RA). In almost all cases, the effects of SC were comparable with those of dexamethasone. In microarray analyses, we identified additional new therapeutic targets of SC. Some of them, such as S100A8, myeloperoxidase, or cathelicidin, an antimicrobial peptide, are known to be implicated in pathophysiological processes in RA. Similar anti-inflammatory effects of SC were also observed in human C28/I2 chondrocyte cells, which are resistant to glucocorticoid treatment. These data indicate that SC and glucocorticoid effects are mediated via independent signal transduction pathways. In summary, we demonstrate that SC is a new effective anti-inflammatory compound that may serve as a lead compound for the development of new drugs for the therapy of chronic inflammatory diseases.
23188554 A study of the link between bone turnover markers and bone mineral density with inflammati 2013 Mar In this study, the levels of bone turnover markers (BTMs) and bone mineral density (BMD) were studied in relation to body mass and several inflammatory markers, in postmenopausal patients with rheumatoid arthritis (RA). Fifty-nine postmenopausal women with active RA (lean, overweight, obese) were studied. The femoral BMD and serum levels of BTMs: osteocalcin (OC) and collagen type I cross-linked C-telopeptide fragments (CTX), and osteopontin (OPN), resistin, high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor (TNF)-α in these patients were measured. It has been noticed that obese women had significantly higher total femoral BMD and total T-score compared to the lean subjects (p ≤ 0.01). The significant associations of BMD measures and CTX levels with body mass parameters (p ≤ 0.01 and p < 0.05, respectively) were found. Values of neck BMD adjusted for BMI were inversely associated with concentrations of TNF-α (p < 0.05). Osteocalcin levels inversely correlated with resistin (p ≤ 0.01) and CTX levels positively correlated with OPN (p ≤ 0.01). There were found no associations between BTMs and BMD with other inflammatory indices. Inverse correlations between OPN levels and body mass (p < 0.05), waist circumference (p < 0.05), and duration of postmenopausal period (p ≤ 0.01) were observed. Findings of the present study suggest that body mass and inflammatory markers, most of all OPN, resistin and TNF-α, play an important role in bone metabolism in postmenopausal women with active RA.
21691913 [Endoprosthetic replacement of the rheumatoid wrist]. 2011 Jul For patients with rheumatoid arthritis preventive and reconstructive surgery of the hand provide better functional results and higher patient satisfaction when surgery is done adequately before the inflammatory stage, especially when multiple joints are affected. Synovectomy, arthrodesis and prosthetic reconstruction are able to guarantee maintenance of function even in late stages and severe destruction, when modern drug therapy cannot prevent further inflammatory attacks and increasing destruction.
22736097 A novel mouse model that develops spontaneous arthritis and is predisposed towards atheros 2013 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) have a reduced life expectancy due to increased cardiovascular disease. The lack of a suitable animal model resembling both RA and atherosclerosis has hindered studies demonstrating a direct link between systemic inflammation in RA and the development of atherosclerosis. Our objective was to overcome this barrier by generating an animal model (K/BxA(g7)) that spontaneously develops both RA-like disease and atherosclerosis. METHODS: Arthritis severity was evaluated using clinical indices and immunohistochemical staining of ankle joint specimens. Aortic atherosclerosis was delineated via Sudan IV staining and immunohistochemical analysis. Serum cholesterol and lipoprotein levels were measured using enzymatic assays. Serum levels of cytokines, chemokines and adipokines were determined by Luminex assays. RESULTS: K/BxA(g7) mice developed a destructive arthropathy followed by prominent aortic atherosclerosis. These animals also displayed dyslipidaemia, characterised by reduced serum levels of total cholesterol and high-density lipoprotein, and increased low-density lipoprotein (LDL)/vLDL compared with control mice. Further, there were higher levels of circulating inflammatory mediators, such as interleukin-6, sRANKL and CCL5 in atherosclerotic K/BxA(g7) mice compared with controls. Treatment with etanercept reduced arthritis and atherosclerosis development in K/BxA(g7) mice. CONCLUSIONS: K/BxA(g7) mice recapitulate the same sequence of events occurring in patients with RA, namely an erosive, inflammatory arthritis followed by atherosclerosis. These data suggest that the K/BxA(g7) mouse is a novel system for investigating the interplay between systemic inflammation occurring in RA and the development of atherosclerosis.
23103817 [Inflammatory cytokines in rheumatoid arthritis]. 2012 Nov Dysregulation of cytokines, including tumor necrosis factor (TNF) and interleukin-6 (IL-6) , is involved in joint destruction in rheumatoid arthritis (RA) . TNF and IL-6 induce the differentiation and activation of osteoclasts. They also provide the formation of pannus through the synthesis of vascular endothelial growth factor (VEGF) . In addition, they contribute to the production of matrix metalloproteinases which digest collagen and proteoglycan of cartilage and bone. Biologic agents targeting these cytokines have provided beneficial outcomes, such as achievement of clinical remission, protective effects against joint destruction, and improvement in quality of life (QOL) in RA patients.
22209079 Targeting TNF superfamily members for therapeutic intervention in rheumatoid arthritis. 2012 Mar Rheumatoid arthritis (RA) is an inflammatory disease is one of the most serious medical problems, affecting ∼1% of all people worldwide, irrespective of race. The disease is autoimmune in nature and characterized by chronic inflammation of the synovial tissues in multiple joints that leads to joint destruction. Although T cells are central players in RA development, B cells are required for full penetrance of disease largely via their production of autoantibodies against Fc domain of IgG rheumatoid factor (RF). Treatment options for RA are limited and if any, are inadequate due to associated side effects. Members of the tumor necrosis factor (TNF) superfamily play important roles in a number of autoimmune diseases, including RA. In this review, we briefly summarize key features of the superfamily, we will consider how the well-characterized members concerned with immune regulation are coordinated and their roles in rheumatoid arthritis.
21463729 Muscle hypoxia in rheumatoid hands: does it play a role in ulnar drift? 2011 Apr PURPOSE: The cause of ulnar drift in patients with rheumatoid arthritis (RA) is unknown. It may occur because of external forces applied to the fingers during normal use. Alternatively, it may arise after changes in the internal forces on the anatomy of the digits owing to alterations in the supporting structures of the joints or their control mechanisms, or both. Intrinsic muscle tightness, which is commonly seen in RA hands, may be the result of adaptive shortening or a direct consequence of RA. Previous studies carried out by our group have shown that joints, tendons, and associated synovium in RA hands are consistently hypoxic. Therefore, we formed the hypothesis that there is a difference in hand/forearm muscle oxygen tension in RA versus non-RA. METHODS: We measured tissue oxygen levels in the intrinsic muscles of the hands and forearm muscles of 29 patients with a diagnosis of RA, who were undergoing elective surgery. We measured oxygen levels using a microelectrode technique. A total of 31 patients without RA undergoing elective surgery served as matched controls. RESULTS: Our results show that the intrinsic muscles of RA patients are significantly more hypoxic than in non-RA controls. Moreover, there is a trend in the RA group for increasing hypoxia in a radial-to-ulnar direction when comparing the different intrinsic muscle groups. We also demonstrate that forearm and thenar and hypothenar muscles are significantly more hypoxic in RA versus non-RA patients. CONCLUSIONS: The intrinsic muscle weakness, intrinsic tightness, and muscle wasting observed in RA may not be due to disuse atrophy resulting from joint disease. From our data, we speculate that these changes may be the result of direct muscular involvement in RA leading to muscle hypoxia.
22247360 Remission in early rheumatoid arthritis: predicting treatment response. 2012 Mar OBJECTIVE: Optimizing therapeutic strategies to induce remission requires an understanding of the initial features predicting remission. Currently no suitable model exists. We aim to develop a remission score using predictors of remission in early rheumatoid arthritis (RA). METHODS: We used a dataset from a UK randomized controlled trial that evaluated intensive treatment with conventional combination therapy, to develop a predictive model for 24-month remission. We studied 378 patients in the trial who received 24 months' treatment. Our model was validated using data from a UK observational cohort (Early RA Network, ERAN). A group of 194 patients was followed for 24 months. Remission was defined as 28-joint Disease Activity Score < 2.6. Logistic regression models were used to estimate the associations between remission and potential baseline predictors. RESULTS: Multivariate logistic regression analyses showed age, sex, and tender joint count (TJC) were independently associated with 24-month remission. The multivariate remission score developed using the trial data correctly classified 80% of patients. These findings were replicated using ERAN. The remission score has high specificity (98%) but low sensitivity (13%). Combining data from the trial and ERAN, we also developed a simplified remission score that showed that younger men with a TJC of 5 or lower were most likely to achieve 24-month remission. Remission was least likely in older women with high TJC. Rheumatoid factor, rheumatoid nodules, and radiographic damage did not predict remission. CONCLUSION: Remission can be predicted using a score based on age, sex, and TJC. The score is relevant in clinical trial and routine practice settings.
22135142 Active foot synovitis in patients with rheumatoid arthritis: applying clinical criteria fo 2012 May OBJECTIVE: To determine whether application of criteria for remission in rheumatoid arthritis (RA) may result in underestimation of foot joint involvement among patients in a clinic setting. METHODS: RA patients (n = 123) were assessed at baseline and 6 months after commencement of a response-driven combination disease-modifying antirheumatic drug (DMARD) protocol. Remission was assessed using disease activity measures (the 28-joint Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index [CDAI]) as well as Boolean-based criteria for remission (the 1981 American College of Rheumatology [ACR] preliminary criteria and the 2011 ACR/European League Against Rheumatism [EULAR] provisional criteria). The prevalence of foot synovitis and the mean swollen/tender foot joint count in RA patients meeting any of these remission criteria were estimated by hurdle (mixed distribution) regression. RESULTS: In patients who received 6 months of combination DMARD treatment, application of the 1981 ACR criteria and the newly proposed 2011 ACR/EULAR criteria, each utilizing full joint counts (which includes assessment of the feet), classified the least number of patients as being in remission (8-10%), and evidence of foot synovitis was minimal among these patients. In contrast, ongoing foot synovitis was present in a substantial proportion of patients (>20%) meeting the 28-joint count criteria for remission, including the DAS28-ESR, SDAI, CDAI, and 2011 ACR/EULAR criteria (clinical practice setting or clinical trials). Furthermore, applying the 2011 ACR/EULAR composite remission criterion of a SDAI score ≤3.3 to define remission did not adequately capture the resolution of foot synovitis (i.e., residual foot involvement was still detected in a substantial proportion of patients classified as being in remission by this definition). CONCLUSION: Although the DAS28-ESR, CDAI, and SDAI have been validated for assessment of remission in RA, this study shows that the performance of these 3 disease activity measures, which do not provide a direct assessment of the foot, in detecting foot synovitis is poor, in contrast to that of the 1981 ACR and 2011 ACR/EULAR remission criteria utilizing full joint counts. Thus, patients may be at risk of ongoing damage if treatment decisions are made solely on the basis of criteria that omit foot joint assessment.
22932980 [Extra-articular manifestations of rheumatoid arthritis]. 2012 Dec Rheumatoid arthritis (RA) represents an autoimmune disease affecting mostly joints, in particular small finger and toe joints. In addition RA can show extra-articular manifestations in many organs. Information on the frequency of extra-articular manifestations (EAMs) in RA varies greatly in different publications from 17.8% to 40.9% and EAMs tend to become higher with increasing duration and severity of the disease. The exact etiology and pathogenesis are still unclear but vasculitic alterations together with deposition of immune complexes can often be found histopathologically in affected organs. It must also be taken into consideration that EAMs can also be a result of the pharmaceutical therapy. The organ findings can vary greatly which is also reflected in the multitude of clinical symptoms. Possible target organs are the blood vessels, kidneys, central nervous system, cardiovascular system, the lungs, eyes, skin, nails as well as blood and the hemopoetic system. The prognosis for RA becomes progressively worse in the presence of EAMs. Regular and continuous control investigations are necessary in order to be able to diagnose EAMs early and to begin therapy. Therapy includes the administration of non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) and especially in advanced stages cyclophosphamide or biologicals. Therapy is still very empirical due to the lack of appropriate studies.
21177292 Different stages of rheumatoid arthritis: features of the synovium in the preclinical phas 2011 May BACKGROUND: The aetiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. It is currently unknown whether the disease process starts in the synovium, the primary target of RA, or at other sites in the body. OBJECTIVE: To examine, in a prospective study, the presence of synovitis in people with an increased risk of developing RA. METHODS: Thirteen people without evidence of arthritis, who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies, were included in the study. To evaluate synovial inflammatory changes, all participants underwent dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion. Results were compared with knee MRI data and synovial biopsy data of 6 and 10 healthy controls, respectively. RESULTS: MRI findings evaluated by measurement of maximal enhancement, rate of enhancement, synovial volume and enhancement shape curve distribution were similar between the autoantibody-positive subjects and the healthy controls. Consistent with these findings, all but one autoantibody-positive subject showed very low scores for phenotypic markers, adhesion molecules and vascularity, all in the same range as those in normal controls. The one person with higher scores had patellofemoral joint space narrowing. CONCLUSION: Subclinical inflammation of the synovium does not coincide with the appearance of serum autoantibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a 'second hit' is involved. This study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.
22411018 Acute atraumatic hip dislocation in an adult with rheumatoid arthritis. 2012 Apr There are no reports of atraumatic hip subluxation and dislocation in the adult patient with rheumatoid arthritis (RA). This rare phenomenon is most prevalent in patients with congenital hip dislocation, von Recklinghausen disease, tumor infiltration, connective tissue disorders, and juvenile rheumatoid arthritis. We report an acute atraumatic dislocation of the hip in an adult patient with RA. We believe that two factors contributed to the patient's atraumatic dislocation: a shallow but appropriately positioned acetabulum and erosive RA with substantiate panus formation. Similar to previous reports, there was a rent or capsular defect that may have contributed to the mechanism of dislocation. Physicians should be aware that, although rare, a de novo atraumatic hip dislocation is a possibility in a patient with a long-standing history of RA and hip pain. Distinguishing features of this case include the acuteness of the dislocation, the absence of previous symptoms, and adult-onset RA.
21447567 Clinical predictors of erosion-free status in rheumatoid arthritis: a prospective cohort s 2011 Aug OBJECTIVE: Treatment algorithms in RA include factors associated with poor prognosis; however, many patients remain erosion free despite years of disease. Our objective was to characterize the group of RA patients without erosions and identify its clinical predictors. METHODS: Our study was conducted within a prospective observational cohort of RA patients recruited from the outpatient practice of an academic medical centre. We studied patients with bilateral hand radiographs at cohort baseline and 2-year follow-up assessed with Sharp/van der Heijde scores (SHS). The primary outcome was erosion-free status at baseline and 2-year follow-up. We assessed baseline values of the following as potential correlates: age at RA onset, gender, RA duration, BMI, 28-joint DAS (DAS-28), CRP, anti-CCP status, tender and swollen joint counts, functional status [multidimensional HAQ (MDHAQ)], tobacco use and RA treatments. Variables with P ≤ 0.25 in the univariate analyses were assessed using backward selection in multivariable logistic regression models. RESULTS: Of the 271 subjects included, 21% (n = 56) were considered erosion free. Forty-six per cent (n = 26) of this group was anti-CCP positive compared with 56% (n = 121) in subjects with erosions present. Mean RA duration for erosion-free subjects was 3.9 years compared with 4.6 years in erosive subjects. Treatments for RA did not differ between the two groups. In the multivariable-adjusted analysis, significant predictors of erosion-free status were younger age at onset and shorter RA duration. CONCLUSION: In our cohort, 21% of subjects were erosion free at baseline and 2 years. Few baseline clinical characteristics significantly predicted erosion-free status.
22588813 Vitamin D deficiency in rheumatoid arthritis. Prevalence and association with disease acti 2012 May OBJECTIVE: To estimate the prevalence of low serum vitamin D level (25[OH]D) in patients with rheumatoid arthritis (RA) compared with healthy controls, and to analyze the association between 25(OH)D and disease activity. METHODS: This retrospective analysis included 100 RA patients (85% women) and 100 controls, not on vitamin D supplements from January 2010 to December 2011 at a tertiary care center at the Department of Internal Medicine, King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia. Disease activity was measured using the disease activity score index (DAS28). According to the DAS28 score, RA patients were divided into 3 groups as high, moderate, and low disease activity. Patients' serum 25(OH)D was measured in a centralized laboratory. RESULTS: The mean 25(OH)D in patients with RA was similar to the control group (32.3+/-14.4 nmol/L) versus (31.4+/-16.4 nmol/L) (p=0.41). Patients with high disease activity had the lowest 25(OH)D levels (18.25+/-8.3 nmol/L) compared with patients with moderate (35.13+/-15.2 nmol/L) and low (38.05+/-7.3 nmol/L) disease activity (p<0.001). Serum 25(OH)D was negatively correlated with DAS28, which was statistically significant (r= -0.42, p<0.0001). CONCLUSION: Serum vitamin D levels in RA patients were similar to the healthy control group. However, significantly lower 25(OH)D values were found in patients who are poorly responding to treatment, and not in a state of disease remission.
21901378 Using mixed methods research to explore the effect of an adaptation exercise on general po 2012 Apr PURPOSE: To understand the effect of an adaptation exercise (AE) on general population values for rheumatoid arthritis (RA) states. METHODS: A sequential mixed methods design was employed: an analysis of a dataset to develop RA states for valuing in later phases of the study; a qualitative interview study with members of the general population to identify how an AE affected valuing of the RA states and to help design a questionnaire for the final phase; and a quantitative quasi-experimental study to identify factors that influence change in values after being informed about adaptation. RESULTS: Three RA states were developed using Rasch and cluster analyses. Participants in the qualitative phase identified a range of ways in which information about adaptation affected their values. For example, they realized they could adapt to RA because their family and friends who had RA, or similar conditions, could cope. A 25-item questionnaire was developed and used during the final phase to identify that younger and healthier individuals were more likely to increase their values after being informed about disease adaptation. The qualitative findings were revisited and found to support the quantitative results. CONCLUSIONS: This approach facilitated understanding of whether and how an AE affected valuing of health states. Each phase affected the next phase of the study, leading to the conclusion that general population respondents who have little experience of disease will likely increase their health state values after being informed about adaptation because they understand that they could cope with the disease.
23052404 [Therapy of rheumatoid arthritis with methotrexate. Claims data analysis of treatment patt 2012 Dec Methotrexate (MTX) is the most important disease-modifying antirheumatic drug (DMARD) and is recommended by national and international guidelines as the first choice for treatment of rheumatoid arthritis (RA). Recent studies reporting prescription data of MTX captured only patients who were treated by rheumatologists. Therefore, the aim of the present study was to analyse several aspects of the prescription of MTX based on claims data. Outpatient and inpatient diagnoses as well as prescription data was available for 9579 RA patients for the years 2005-2008. Of the patients 45% were treated exclusively with parenteral MTX, 8% were treated exclusively with oral MTX and 48% switched between both forms of application. The average weekly dosage presribed in 70% of the patients was between 10 and 25 mg. The most common DMARD combination was MTX plus leflunomide with 16%. In 16% RA patients were treated with a combination of MTX and TNF-α inhibitors. Glucocorticoids were prescribed temporarily in 81% together with MTX and supplementation with folic acid was given only in 65%. The results of this study provide important insights into the drug supply of MTX to RA patients in the German statutory health care sector. In particular, the high frequency of prescriptions of parenteral MTX and the inadequate prescription of folic acid are different from the recently published multinational recommendations of the 3E initiative for the use of MTX.
23231716 Immune regulation in idiopathic bronchiectasis. 2012 Dec Bronchiectasis is a complex pathological endpoint arrived at through a diverse interplay between lung infection and altered immune function. It comprises irreversible, abnormal dilatation of one or more bronchi, with chronic airway inflammation and is associated with recurrent chest infections, airflow obstruction, chronic cough, excessive sputum production, and malaise. Many pathogens are associated with this disease, including chronic bacterial infections, nontuberculous mycobacteria, and aspergillis. However, the etiology is poorly defined. Disease-associated genes indicate a likely contribution to disease mechanism both from innate and adaptive immunity. The role of immune mechanisms is highlighted by the occurrence of bronchiectasis in a subset of patients with rheumatoid arthritis or inflammatory bowel disease as well as diseases of immune dysregulation such as combined variable immune deficiency, transporter associated with antigen processing (TAP) deficiency syndrome, and hyper-IgE syndrome. Recent evidence indicates a possible role of excessive natural killer cell activation in pathogenesis.
21890656 Experimental arthritis triggers periodontal disease in mice: involvement of TNF-α and the 2011 Oct 1 Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic inflammatory disorders that affect bone structures. Individuals with RA are more likely to experience PD, but how disease in joints could induce PD remains unknown. This study aimed to experimentally mimic clinical parameters of RA-induced PD and to provide mechanistic findings to explain this association. Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA in the knee joint of immunized mice. Anti-TNF-α was used to assess the role of this cytokine. Intra-articular challenge induced infiltration of cells, synovial hyperplasia, bone resorption, proteoglycan loss, and increased expression of cytokines exclusively in challenged joints. Simultaneously, AIA resulted in severe alveolar bone loss, migration of osteoclasts, and release of proinflammatory cytokines in maxillae. Anti-TNF-α therapy prevented the development of both AIA and PD. AIA did not modify bacterial counts in the oral cavity. PD, but not AIA, induced by injection of Ag in immunized mice was decreased by local treatment with antiseptic, which decreased the oral microbiota. AIA was associated with an increase in serum C-reactive protein levels and the expression of the transcription factors RORγ and Foxp3 in cervical lymph nodes. There were higher titers of anti-collagen I IgG, and splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA-induced PD was dependent on TNF-α and the oral microbiota. Moreover, PD was associated with changes in expression of lymphocyte transcription factors, presence of anti-collagen Abs, and increased reactivity to autoantigens.
23229747 Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammatio 2013 Feb PURPOSE: This study evaluated the potential of functional imaging to monitor disease activity and response to treatment with disease-modifying antirheumatic drugs (DMARD) in DMARD-naive patients with early rheumatoid arthritis (RA). METHODS: The study involved 17 patients with active RA in whom combination therapy was initiated with methotrexate, sulfasalazine, hydroxychloroquine, and low-dose oral prednisolone. Clinical disease activity was assessed at screening, at baseline and after 2, 4, 8 and 12 weeks of therapy. (18)F-FDG PET/CT of all joints was performed at baseline and after 2 and 4 weeks of therapy. RESULTS: (18)F-FDG maximum standardized uptake values showed a reduction of 22 ± 13 % in 76 % of patients from baseline to week 2 and a reduction of 29 ± 13 % in 81 % of patients from baseline to week 4. The percentage decrease in (18)F-FDG uptake from baseline to week 2 correlated with clinical outcome, as measured by the disease activity score (DAS-28) at week 12. In addition, changes in C-reactive protein levels and erythrocyte sedimentation rate were positively associated with changes shown by PET. CONCLUSION: (18)F-FDG PET/CT findings after 2 and 4 weeks of triple combination oral DMARD therapy correlated with treatment efficacy and clinical outcome in patients with early RA. (18)F-FDG PET/CT may help predict the therapeutic response to novel drug treatments.
21994440 Surrogate outcomes are associated with low methodological quality of studies of rheumatoid 2012 Feb BACKGROUND: Surrogate endpoints may be used as substitutes for, but often do not predict clinically relevant events. Objective To assess the methodological quality of articles that present their conclusions based on clinically relevant or surrogate outcomes in a systematic review of randomised trials and cohort studies of patients with rheumatoid arthritis treated with antitumour necrosis factor (TNF) agents. METHODS: PubMed, Embase and Cochrane databases were searched. The Jadad score, the percentage of Consolidated Standards Of Reporting Trials (CONSORT) statement items adequately reported and levels-of-evidence (Center for Evidence-based Medicine, Oxford) were used in a descriptive synthesis. RESULTS: Among 88 articles appraised, 27 had surrogate endpoints, mainly radiographic, and 44 were duplicate publications; 74% of articles with surrogate and 39% of articles with clinical endpoints (p=0.006). Fewer articles with surrogate endpoints represented a high level of evidence (Level 1b, 33% vs 62%, p=0.037) and the mean percentage of CONSORT statement items met was also lower for articles with surrogate endpoints (62.5 vs 70.7, p=0.026). Although fewer articles with surrogate endpoints were randomised trials (63% vs 74%, p=0.307) and articles with surrogate endpoints had lower Jadad scores (3.0 vs 3.2, p=0.538), these differences were not statistically significant. CONCLUSION: Studies of anti-TNF agents that report surrogate outcomes are of lesser methodological quality. As such, inclusion of such studies in evidence syntheses may bias results.