Objective To investigate the relationships between several health outcomes in ankylosing spondylitis (AS). Methods Baseline pretreatment data from 214 patients with AS participating in the AS Study... Show moreObjective To investigate the relationships between several health outcomes in ankylosing spondylitis (AS). Methods Baseline pretreatment data from 214 patients with AS participating in the AS Study for the Evaluation of Recombinant Infliximab Therapy were analysed. Measures of health-related quality of life (HRQoL) and physical function were used as dependent variables in linear regression analysis. Associations between HRQoL (36-Item Short Form (SF-36)), physical function, clinical disease activity, spinal mobility, structural damage, MRI inflammation, disease duration, age, gender, body mass index and HLA-B27 were explored. Univariate associations were retested in multivariate models. The robustness of the models was evaluated by sensitivity analyses. Results The physical component of SF-36 was independently associated with measures of physical function and disease activity (adjusted R 2 (adjR 2)= 0.39-0.40). The mental component of SF-36 was independently associated with physical function (adjR 2 = 0.07). Physical function was independently associated with measures of spinal mobility and disease activity (adjR 2 = 0.39-0.45). Spinal mobility was hierarchically shown to be an intermediate variable between structural damage and physical function, while physical function was shown to be intermediate between spinal mobility and the physical component of SF-36. Conclusion According to the proposed stratified model for health outcomes in AS, HRQoL is determined by physical function and disease activity, physical function is determined by spinal mobility and disease activity, and spinal mobility is determined by structural damage and inflammation of the spine. As more is learnt about how to measure AS, knowledge about the disease improves and better decisions can be made on the assessment and treatment of this disease. Show less
Braun, J.; Heijde, D. van der; Hermann, K.G.; Baraliakos, X.; Deodhar, A.; Beutler, A.; ... ; GO-RAISE Clinical Investigators 2011
OBJECTIVE: To investigate the relationship between MRI inflammation at the vertebral unit and the formation and growth of syndesmophytes at the same vertebral unit.METHODS: An 80% random sample of... Show moreOBJECTIVE: To investigate the relationship between MRI inflammation at the vertebral unit and the formation and growth of syndesmophytes at the same vertebral unit.METHODS: An 80% random sample of the ASSERT database was analysed. MRI were scored using the ankylosing spondylitis (AS) spinal MRI activity score (at baseline, 24 and 102 weeks) and spinal x-rays were scored using the modified Stoke AS spine score (at baseline and 102 weeks). Data were analysed at the patient level and the vertebral unit level using a multilevel approach to adjust for within-patient correlation.RESULTS: There was a slightly increased probability of developing syndesmophytes in vertebral units with MRI activity, which was maintained after adjustment for within-patient correlation (per vertebral unit level) and treatment, and after further adjustment for potential confounders, resulting in significant OR ranging from 1.51 to 2.26. Growth of existing syndesmophytes at the vertebral unit level was not associated with MRI activity. At the patient level only a trend for an association was observed.CONCLUSION: MRI inflammation in a vertebral unit slightly increases the propensity to form a new syndesmophyte in the same vertebral unit, but does not predict the growth of already existing syndesmophytes. Despite this association, the large majority of new syndesmophytes developed in vertebral units without inflammation. The subtle association at the vertebral unit level did not translate into an association at the patient level. Show less
The ASAS/OMERACT MRI group recently described and defined magnetic resonance imaging (MRI) findings in sacroiliac joints (SIJ) that are essential for the diagnosis of sacroiliitis in patients with... Show moreThe ASAS/OMERACT MRI group recently described and defined magnetic resonance imaging (MRI) findings in sacroiliac joints (SIJ) that are essential for the diagnosis of sacroiliitis in patients with axial spondyloarthritis, including ankylosing spondylitis (AS). At the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 2010 meeting, a special interest group (SIG) was formed to design a research agenda for the definition and description of structural lesions in the SIJ and the spine in patients with established AS. During the SIG, a summary of the previous work of the group was presented to all participants, containing: (1) a description of the current definitions of structural SIJ changes; (2) available scoring methods for SIJ changes; (3) data from a previous pilot MRI exercise on chronic SU changes performed by members of the group; and (4) a proposal for a research agenda for OMERACT 11. The group agreed on the project's scientific merits and the need to evaluate all available scoring methods and to have clear definitions for all possible abnormalities that can be seen on MRI, prior to the start of the exercise. It was also agreed that the exercise should include scoring of both structural and inflammatory lesions, due to lack of agreement about the best scoring method for assessing both types of lesions in AS. Participants agreed that longitudinal MRI over a certain period are needed to learn about the time sequence of pathologic changes and to understand the course of the disease. Finally, participants asked the group to add the development of a scoring method for structural changes in the spine in a subsequent exercise. Further to these objectives, all experts who agreed to contribute in the exercise will collaborate to achieve consensus on definitions and to organize training in the different scoring systems prior to the start of the project, with the aim to finalize the multiple reader exercise by the end of 2011, in time for OMERACT 11. (J Rheumatol 2011;38:2051-4; doi:10.3899/jrheum.110423) Show less
Adult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured... Show moreAdult epicardial cells are required for endogenous cardiac repair. After myocardial injury, they are reactivated, undergo epithelial-to-mesenchymal transformation (EMT) and migrate into the injured myocardium where they generate various cell types, including coronary smooth muscle cells and cardiac interstitial fibroblasts, which contribute to cardiac repair. To understand what drives epicardial EMT, we used an in vitro model for human adult epicardial cells. These cells have an epithelium-like morphology and markedly express the cell surface marker vascular cell adhesion marker (VCAM-1). In culture, epicardial cells spontaneously undergo EMT after which the spindle-shaped cells now express endoglin. Both epicardial cells before and after EMT express the epicardial marker, Wilms tumor 1 (WT1). Adding transforming growth factor beta (TGF beta) induces loss of epithelial character and initiates the onset of mesenchymal differentiation in human adult epicardial cells. In this study, we show that TGF beta-induced EMT is dependent on type-1 TGF beta receptor activity and can be inhibited by soluble VCAM-1. We also show that epicardial-specific knockdown of Wilms tumor-1 (WT1) induces the process of EMT in human adult epicardial cells, through transcriptional regulation of platelet-derived growth factor receptor alpha (Pdgfr alpha), Snai1 and VCAM-1. These data provide new insights into the process of EMT in human adult epicardial cells, which might provide opportunities to develop new strategies for endogenous cell-based cardiac repair. Show less
This first up date of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the... Show moreThis first up date of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in de tail and reworded if necessary. Decisions on new recommendations were made - if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good. Show less
Heijde, D. van der; Sieper, J.; Maksymowych, W.P.; Dougados, M.; Burgos-Vargas, R.; Landewe, R.; ... ; Assessment SpondyloArthritis Int S 2011
This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients... Show moreThis paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS axial SpA criteria, which also include patients fulfilling the modified New York criteria for ankylosing spondylitis, can be treated with anti-TNF agents. This makes an earlier start in the disease process possible. A second major change is the mandatory pretreatment before anti-TNF agents can be started. All patients should have tried a minimum of two non-steroidal anti-inflammatory drugs for a minimum of 4 weeks in total. This is significantly shorter than the previous requirement of 3 months. As previously, patients with axial symptoms require no further pretreatment. Patients with symptomatic peripheral symptoms should normally have had an adequate therapeutic trial of a disease-modifying antirheumatic drug, preferably sulfasalazine. Sulfasalazine is no longer mandatory in this group of patients. Finally, efficacy should be evaluated after at least 12 weeks. The remaining recommendations stayed largely unchanged. Show less
This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients... Show moreThis paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS axial SpA criteria, which also include patients fulfilling the modified New York criteria for ankylosing spondylitis, can be treated with anti-TNF agents. This makes an earlier start in the disease process possible. A second major change is the mandatory pretreatment before anti-TNF agents can be started. All patients should have tried a minimum of two non-steroidal anti-inflammatory drugs for a minimum of 4 weeks in total. This is significantly shorter than the previous requirement of 3 months. As previously, patients with axial symptoms require no further pretreatment. Patients with symptomatic peripheral symptoms should normally have had an adequate therapeutic trial of a disease-modifying antirheumatic drug, preferably sulfasalazine. Sulfasalazine is no longer mandatory in this group of patients. Finally, efficacy should be evaluated after at least 12 weeks. The remaining recommendations stayed largely unchanged. Show less
Vastesaeger, N.; Heijde, D. van der; Inman, R.D.; Wang, Y.X.; Deodhar, A.; Hsu, B.; ... ; Braun, J. 2011
Objectives To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease... Show moreObjectives To create a model that provides a potential basis for candidate selection for anti-tumour necrosis factor (TNF) treatment by predicting future outcomes relative to the current disease profile of individual patients with ankylosing spondylitis (AS). Methods ASSERT and GO-RAISE trial data (n=635) were analysed to identify baseline predictors for various disease-state and disease-activity outcome instruments in AS. Univariate, multivariate, receiver operator characteristic and correlation analyses were performed to select final predictors. Their associations with outcomes were explored. Matrix and algorithm-based prediction models were created using logistic and linear regression, and their accuracies were compared. Numbers needed to treat were calculated to compare the effect size of anti-TNF therapy between the AS matrix subpopulations. Data from registry populations were applied to study how a daily practice AS population is distributed over the prediction model. Results Age, Bath ankylosing spondylitis functional index (BASFI) score, enthesitis, therapy, C-reactive protein (CRP) and HLA-B27 genotype were identified as predictors. Their associations with each outcome instrument varied. However, the combination of these factors enabled adequate prediction of each outcome studied. The matrix model predicted outcomes as well as algorithm-based models and enabled direct comparison of the effect size of anti-TNF treatment outcome in various subpopulations. The trial populations reflected the daily practice AS population. Conclusion Age, BASFI, enthesitis, therapy, CRP and HLA-B27 were associated with outcomes in AS. Their combined use enables adequate prediction of outcome resulting from anti-TNF and conventional therapy in various AS subpopulations. This may help guide clinicians in making treatment decisions in daily practice. Show less
Vastesaeger, N.; Heijde, D. van der; Inman, R.; Wang, Y.X.; Deodhar, A.; Hsu, B.; ... ; Braun, J. 2011
