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Joachim Sieper - One of the best experts on this subject based on the ideXlab platform.
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Treatment of Axial Spondyloarthritis: What Does the Future Hold?
Current rheumatology reports, 2020Co-Authors: Denis Poddubnyy, Joachim SieperAbstract:Purpose of review To provide a summary of the recent and expected developments related to the treatment of axial Spondyloarthritis. Recent findings An increasing number of interleukin-17 blocking agents show efficacy in axial Spondyloarthritis including both non-radiographic and radiographic forms. Janus kinase inhibitors showed promising results in phase II studies in radiographic axial Spondyloarthritis and have, therefore, a potential to become a therapeutic option in this indication in the future. Inhibition of structural damage progression in axial Spondyloarthritis seems to be possible in the case of effective and early anti-inflammatory treatment, although there are still open questions related to particular drug classes. Despite major advances in the field and growing therapeutic options, there are still many open questions related to the optimized treatment strategies and to the individual choice of a drug in axial Spondyloarthritis.
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ixekizumab an interleukin 17a antagonist in the treatment of ankylosing spondylitis or radiographic axial Spondyloarthritis in patients previously untreated with biological disease modifying anti rheumatic drugs coast v 16 week results of a phase 3 r
The Lancet, 2018Co-Authors: Desiree Van Der Heijde, M Dougados, Joachim Sieper, Atul Deodhar, Walter P. Maksymowych, Tetsuya Tomita, Philip J Mease, Filip Van Den Bosch, Robert Landewe, Fangyi ZhaoAbstract:Summary Background Biological disease-modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial Spondyloarthritis, otherwise known as ankylosing spondylitis, when conventional therapies are not effective. We report efficacy and safety data on ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A (IL-17A), in patients with radiographic axial Spondyloarthritis who have not previously been treated with bDMARDs. Methods In this phase 3, randomised, double-blind, placebo-controlled superiority study of ixekizumab, adult patients with inadequate response or intolerance to non-steroidal anti-inflammatory drugs, an established diagnosis of radiographic axial Spondyloarthritis, radiographic sacroiliitis centrally defined by modified New York criteria, and at least one Spondyloarthritis feature according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, were recruited from 84 sites (12 countries) in Europe, Asia, and North America. By use of a computer-generated random sequence, patients were randomly assigned (1:1:1:1) to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference group), or placebo. The primary objective was to compare the proportion of patients achieving an ASAS40 response, a composite measure of clinical improvement in axial Spondyloarthritis, at week 16 for both ixekizumab treatment groups versus the placebo group. The adalimumab reference group was included as an in-study active reference for comparison with placebo to provide additional context to interpretation of the ixekizumab study results. Findings Between June 20, 2016, and Aug 22, 2017, 341 patients were randomly assigned to either the placebo group (n=87), adalimumab group (n=90), ixekizumab Q2W (n=83), or ixekizumab Q4W (n=81). At week 16, compared with placebo (16 [18%] of 87), more patients achieved ASAS40 with ixekizumab Q2W (43 [52%] of 83; p Interpretation Each dosing regimen of ixekizumab was superior to placebo for improving radiographic axial Spondyloarthritis signs and symptoms in patients not previously treated with bDMARDs; the safety profile was consistent with previous indications of ixekizumab. Funding Eli Lilly and Company
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efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non radiographic axial Spondyloarthritis ability 3 a multicentre randomised double blind study
The Lancet, 2018Co-Authors: R Landewe, Joachim Sieper, Robert G. Lambert, Philip J Mease, Robert D Inman, A Deodhar, H Marzoortega, Marina Magrey, U Kiltz, X WangAbstract:Summary Background Success of treatment withdrawal in patients with non-radiographic axial Spondyloarthritis who are in remission remains unknown. The ABILITY-3 study explored the ability to withdraw adalimumab treatment in patients with non-radiographic axial Spondyloarthritis who achieved sustained clinical remission after open-label treatment with adalimumab. Methods ABILITY-3 was a multicentre, two-period study done in 107 sites in 20 countries. We enrolled adult patients (≥18 years) diagnosed with non-radiographic axial Spondyloarthritis, fulfilling Assessment of Spondyloarthritis international Society classification criteria but not the modified New York radiologic criterion, who had objective evidence of active inflammation, active disease, and inadequate response to at least two non-steroidal anti-inflammatory drugs. Patients who achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease ( Findings Between June 27, 2013, and October 22, 2015, 673 patients were enrolled to the study. The trial completed on April 14, 2017. Of 673 enrolled patients, 305 (45%) achieved sustained remission and were randomly assigned to double-blind treatment (152 patients to adalimumab and 153 to placebo). A greater proportion of patients continuing adalimumab than those receiving placebo did not experience a flare (107 [70%] of 152 patients vs 72 [47%] of 153 patients; p vs 20 [13%]), upper respiratory tract infection (20 [13%] vs 12 [8%]), and worsening of axial Spondyloarthritis (ten [7%] vs 21 [14%]). Interpretation In patients with active non-radiographic axial Spondyloarthritis who achieved sustained remission with adalimumab, continued therapy was associated with significantly fewer patients flaring than was treatment withdrawal. Funding AbbVie.
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Axial Spondyloarthritis.
Lancet (London England), 2017Co-Authors: Joachim Sieper, Denis PoddubnyyAbstract:The term axial Spondyloarthritis covers both patients with non-radiographic and radiographic axial Spondyloarthritis, which is also termed ankylosing spondylitis. The disease usually starts in the third decade of life with a male to female ratio of two to one for radiographic axial Spondyloarthritis and of one to one for non-radiographic axial Spondyloarthritis. More than 90% heritabilty has been estimated, the highest genetic association being with HLA-B27. The pathogenic role of HLA-B27 is still not clear although various hypotheses are available. On the basis of evidence from trials the cytokines tumour necrosis factor (TNF)-α and interleukin-17 appear to have a relevant role in pathogenesis. The mechanisms of interaction between inflammation and new bone formation is still not completely understood but clarification will be important for the prevention of long-term structural damage of the bone. The development of new criteria for classification and for screening of patients with axial Spondyloarthritis have been crucial for the early indentification and treatment of such patients, with MRI being the most important existing imaging method. Non-steroidal anti-inflammatory drugs and TNF blockers are effective therapies. Blockade of interleukin-17 is a new and relevant treatment option.
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Axial Spondyloarthritis.
Nature reviews. Disease primers, 2015Co-Authors: Joachim Sieper, Jurgen Braun, Maxime Dougados, Dominique BaetenAbstract:The term axial Spondyloarthritis covers both non-radiographic disease and radiographic disease (also known as ankylosing spondylitis). Some studies have been performed to investigate the prevalence of axial Spondyloarthritis, although most are limited to patients with radiographic disease. A strong genetic association has been shown between axial Spondyloarthritis and human leukocyte antigen-B27 (HLA-B27), but the pathogenetic role of HLA-B27 has not yet been clarified. Tumour necrosis factor (TNF), IL-17, IL-23 and downstream pathways also seem to be important - based on the good results of therapies directed against these molecules - but their exact role in the inflammatory process is also not yet clear. Elucidating the interaction between osteoproliferation and inflammation will be crucial for the prevention of long-term structural damage of the bone. The development of new criteria for classification, diagnosis and screening of patients with axial Spondyloarthritis will enable earlier intervention for this chronic inflammatory disease. MRI has become an important tool for the early detection of axial Spondyloarthritis. NSAIDs and TNF blockers are effective therapies, including in the early non-radiographic stage. Therapeutic blockade of IL-17 or IL-23 seems to be a promising new treatment option. Tools for measuring quality of life in axial Spondyloarthritis have become relevant to assess the impact that the disease has on patients. These diagnostic and therapeutic advances will continue to change the management of axial Spondyloarthritis, and new insights into the disease pathogenesis will hopefully accelerate this process. For an illustrated summary of this Primer, visit: http://go.nature.com/51b1af.
Jurgen Braun - One of the best experts on this subject based on the ideXlab platform.
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Spondyloarthropathies: How should axial Spondyloarthritis be diagnosed?
Nature reviews. Rheumatology, 2017Co-Authors: Jurgen Braun, Uta KiltzAbstract:Results from a cohort study are challenging the diagnostic algorithm proposed by the Assessment of Spondyloarthritis International Society by showing that rheumatologists are not always confirming a diagnosis of axial Spondyloarthritis in patients with multiple features of Spondyloarthritis. How will these results affect the future development of classification criteria?
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Axial Spondyloarthritis.
Nature reviews. Disease primers, 2015Co-Authors: Joachim Sieper, Jurgen Braun, Maxime Dougados, Dominique BaetenAbstract:The term axial Spondyloarthritis covers both non-radiographic disease and radiographic disease (also known as ankylosing spondylitis). Some studies have been performed to investigate the prevalence of axial Spondyloarthritis, although most are limited to patients with radiographic disease. A strong genetic association has been shown between axial Spondyloarthritis and human leukocyte antigen-B27 (HLA-B27), but the pathogenetic role of HLA-B27 has not yet been clarified. Tumour necrosis factor (TNF), IL-17, IL-23 and downstream pathways also seem to be important - based on the good results of therapies directed against these molecules - but their exact role in the inflammatory process is also not yet clear. Elucidating the interaction between osteoproliferation and inflammation will be crucial for the prevention of long-term structural damage of the bone. The development of new criteria for classification, diagnosis and screening of patients with axial Spondyloarthritis will enable earlier intervention for this chronic inflammatory disease. MRI has become an important tool for the early detection of axial Spondyloarthritis. NSAIDs and TNF blockers are effective therapies, including in the early non-radiographic stage. Therapeutic blockade of IL-17 or IL-23 seems to be a promising new treatment option. Tools for measuring quality of life in axial Spondyloarthritis have become relevant to assess the impact that the disease has on patients. These diagnostic and therapeutic advances will continue to change the management of axial Spondyloarthritis, and new insights into the disease pathogenesis will hopefully accelerate this process. For an illustrated summary of this Primer, visit: http://go.nature.com/51b1af.
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Opinion: Perspectives on imaging in axial Spondyloarthritis.
Nature reviews. Rheumatology, 2013Co-Authors: Xenofon Baraliakos, Jurgen BraunAbstract:Imaging is central for the classification and diagnosis of axial Spondyloarthritis, as well as for monitoring disease progression and predicting response to treatment. Xenofon Baraliakos and Jurgen Braun provide an overview of the role of imaging for patients with axial Spondyloarthritis and discuss how imaging techniques might influence research and clinical practice in the future.
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rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial Spondyloarthritis
Annals of the Rheumatic Diseases, 2011Co-Authors: Denis Poddubnyy, H Haibel, J Listing, Elisabeth Markerhermann, Henning Zeidler, Jurgen Braun, Martin Rudwaleit, Joachim SieperAbstract:Objective To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial Spondyloarthritis over a period of 2 years and to explore predictors of progression. Methods 210 patients with axial Spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data. Results 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial Spondyloarthritis. More patients with non-radiographic Spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated ‘true’ progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial Spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial Spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p Conclusion Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial Spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.
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Update on biologic therapy in the management of axial Spondyloarthritis.
Current rheumatology reports, 2010Co-Authors: Frank Heldmann, Friedrich Dybowski, Ertan Saracbasi-zender, Claas Fendler, Jurgen BraunAbstract:Axial Spondyloarthritis, which includes ankylosing spondylitis and psoriatic Spondyloarthritis, is an important subtype of the spondyloarthritides. Tumor necrosis factor (TNF) antagonists are effective therapies for this partially heterogeneous group of rheumatic diseases in terms of signs, symptoms, and functioning, but they do not seem to substantially inhibit radiographic progression, which is mainly new bone formation in ankylosing spondylitis. However, they clearly reduce inflammation, as shown by MRI. TNF blockers are also efficacious in the treatment of extraspinal features of Spondyloarthritis. In addition, evidence indicates that anti-TNF therapy works well in early axial disease. Other biologics are currently being investigated, as alternatives are needed for patients who fail anti-TNF therapy.
Daniel Wendling - One of the best experts on this subject based on the ideXlab platform.
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Etanercept for treating axial Spondyloarthritis.
Expert Opinion on Biological Therapy, 2017Co-Authors: Xavier Guillot, Maxime Sondag, Clement Prati, Daniel WendlingAbstract:ABSTRACTIntroduction: Axial Spondyloarthritis is an inflammatory rheumatic disease causing back pain, functional impairment and potential ankylosis in the advanced stage. In this context, TNF blockers have been a major therapeutic advance. Etanercept is a soluble recombinant TNF receptor fusion protein in this vain.Areas covered: The aim of this review is to summarize the current published data concerning the efficacy and tolerance of etanercept in axial spondyloarthrits. The authors performed a systematic review on PubMed, using ‘etanercept’ and ‘Spondyloarthritis’, ‘axial Spondyloarthritis’ or ‘ankylosing spondylitis’ keywords.Expert opinion: Etanercept showed clinical efficacy on the axial (non-radiographic and radiographic) and peripheral manifestations (peripheral arthritis and enthesitis) of axial Spondyloarthritis (Ax-SpA). Among the extra-articular manifestations, it works on psoriasis but not on inflammatory bowel disease, with a lack of efficacy data in anterior uveitis. Etanercept also demonstr...
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Etanercept for treating axial Spondyloarthritis.
Expert Opinion on Biological Therapy, 2017Co-Authors: Xavier Guillot, Maxime Sondag, Clement Prati, Daniel WendlingAbstract:ABSTRACTIntroduction: Axial Spondyloarthritis is an inflammatory rheumatic disease causing back pain, functional impairment and potential ankylosis in the advanced stage. In this context, TNF blockers have been a major therapeutic advance. Etanercept is a soluble recombinant TNF receptor fusion protein in this vain.Areas covered: The aim of this review is to summarize the current published data concerning the efficacy and tolerance of etanercept in axial spondyloarthrits. The authors performed a systematic review on PubMed, using ‘etanercept’ and ‘Spondyloarthritis’, ‘axial Spondyloarthritis’ or ‘ankylosing spondylitis’ keywords.Expert opinion: Etanercept showed clinical efficacy on the axial (non-radiographic and radiographic) and peripheral manifestations (peripheral arthritis and enthesitis) of axial Spondyloarthritis (Ax-SpA). Among the extra-articular manifestations, it works on psoriasis but not on inflammatory bowel disease, with a lack of efficacy data in anterior uveitis. Etanercept also demonstr...
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MRI in axial Spondyloarthritis
2015Co-Authors: Daniel Wendling, Thao Pham, Pascal Claudepierre, Damien Loeuille, Clement PratiAbstract:Magnetic resonance imaging (MRI) has revolutionized the everyday management of Spondyloarthritis, particularly in its axial forms. The ability of MRI to identify characteristic inflammatory changes not only at the sacroiliac joints, but also at the spine has shed new light on the diagnosis of Spondyloarthritis and provided new pathophysiological insights, particularly regarding ossification of the spinal entheses [1]. Thus, sacroiliitis detectable only by MRI was included into the ASAS criteria set in 2009 [2], so that the radiographic sacroiliitis required in the modified New York criteria is no longer mandatory. This change may shorten the time to diagnosis [3] and constitutes official recognition of non-radiographic forms of axial Spondyloarthritis [4], with a new terminology [5]. The unique capabilities of MRI have thus illuminated some of the obscure issues surrounding Spondyloarthritis. Their discovery generated hope that many of the challenges raised by the early diagnosis or objective monitoring of Spondyloarthritis (and therefore by the evaluation of treatments) might find “visible” solutions in everyday practice. Now, several years later, experience has tempered the initial enthusiasm. We must recognize that the studies conducted to date have raised new questions without necessarily solving the initial problems.
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recommendations of the french society for rheumatology sfr on the everyday management of patients with Spondyloarthritis
Joint Bone Spine, 2014Co-Authors: Daniel Wendling, Philippe Goupille, Pascal Claudepierre, C. Lukas, Julien Paccou, L Carton, Bernard Combe, Francis Guillemin, C Hudry, Corinne MicelirichardAbstract:Abstract The management of Spondyloarthritis is challenging and has changed with the development of new concepts and treatments. Objective To develop practice guidelines for the everyday management of patients with Spondyloarthritis (including psoriatic arthritis), by updating previous national and international recommendations, based on a review of recently published data. Methods A task force and a multidisciplinary literature review group were established. The task force identified the issues that remained unresolved. Based on existing recommendations and recent publications, the task force developed practice guidelines, which were revised by the literature review group and graded according to AGREE. Results Practice guidelines for the management of Spondyloarthritis are reported. After a review of the general diagnostic principles, 30 practice guidelines are given: 5 on general principles, 4 on the management strategy, 5 on non-pharmacological treatments, 7 on conventional pharmacological treatments, 6 on biotherapies, and 3 on surgical treatments and follow-up. Conclusion The updated practice guidelines reported here constitute a global framework that can guide physicians in the everyday management of Spondyloarthritis.
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ankylosing spondylitis spondyloarthropathy Spondyloarthritis or spondylarthritis what s in a name
Joint Bone Spine, 2012Co-Authors: Pascal Claudepierre, Daniel Wendling, Maxime Breban, Philippe Goupillle, M DougadosAbstract:Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 30 juillet 2012
Denis Poddubnyy - One of the best experts on this subject based on the ideXlab platform.
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Treatment of Axial Spondyloarthritis: What Does the Future Hold?
Current rheumatology reports, 2020Co-Authors: Denis Poddubnyy, Joachim SieperAbstract:Purpose of review To provide a summary of the recent and expected developments related to the treatment of axial Spondyloarthritis. Recent findings An increasing number of interleukin-17 blocking agents show efficacy in axial Spondyloarthritis including both non-radiographic and radiographic forms. Janus kinase inhibitors showed promising results in phase II studies in radiographic axial Spondyloarthritis and have, therefore, a potential to become a therapeutic option in this indication in the future. Inhibition of structural damage progression in axial Spondyloarthritis seems to be possible in the case of effective and early anti-inflammatory treatment, although there are still open questions related to particular drug classes. Despite major advances in the field and growing therapeutic options, there are still many open questions related to the optimized treatment strategies and to the individual choice of a drug in axial Spondyloarthritis.
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Axial Spondyloarthritis.
Lancet (London England), 2017Co-Authors: Joachim Sieper, Denis PoddubnyyAbstract:The term axial Spondyloarthritis covers both patients with non-radiographic and radiographic axial Spondyloarthritis, which is also termed ankylosing spondylitis. The disease usually starts in the third decade of life with a male to female ratio of two to one for radiographic axial Spondyloarthritis and of one to one for non-radiographic axial Spondyloarthritis. More than 90% heritabilty has been estimated, the highest genetic association being with HLA-B27. The pathogenic role of HLA-B27 is still not clear although various hypotheses are available. On the basis of evidence from trials the cytokines tumour necrosis factor (TNF)-α and interleukin-17 appear to have a relevant role in pathogenesis. The mechanisms of interaction between inflammation and new bone formation is still not completely understood but clarification will be important for the prevention of long-term structural damage of the bone. The development of new criteria for classification and for screening of patients with axial Spondyloarthritis have been crucial for the early indentification and treatment of such patients, with MRI being the most important existing imaging method. Non-steroidal anti-inflammatory drugs and TNF blockers are effective therapies. Blockade of interleukin-17 is a new and relevant treatment option.
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Golimumab for treatment of axial Spondyloarthritis
Immunotherapy, 2016Co-Authors: Valeria Rios Rodriguez, Denis PoddubnyyAbstract:Axial Spondyloarthritis comprises two forms: nonradiographic (nonradiographic axial Spondyloarthritis) and radiographic (better known as ankylosing spondylitis), which are often considered as two stages of one disease. Historically, all currently available TNF-α inhibitors were first investigated in ankylosing spondylitis and later on in nonradiographic axial Spondyloarthritis. This year, EMA has granted golimumab approval for the treatment of active nonradiographic axial Spondyloarthritis based on the recently published data from the GO-AHEAD study. This article summarizes recent data on efficacy and safety of golimumab in the treatment of ankylosing spondylitis and nonradiographic axial Spondyloarthritis.
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similarities and differences between nonradiographic and radiographic axial Spondyloarthritis a clinical epidemiological and therapeutic assessment
Current Opinion in Rheumatology, 2014Co-Authors: Denis Poddubnyy, Joachim SieperAbstract:PURPOSE OF REVIEW: The concept of axial Spondyloarthritis with two forms or subtypes (nonradiographic and radiographic) has been established over the last few years. However, debates concerning especially the nonradiographic form of the disease are still ongoing. Here we summarise recent data on similarities and differences (and their possible explanations) between nonradiographic axial Spondyloarthritis and radiographic axial Spondyloarthritis (ankylosing spondylitis). RECENT FINDINGS: Nonradiographic and radiographic forms are about equally frequent among patients first diagnosed with axial Spondyloarthritis and have in general similar clinical characteristics, especially related to clinical signs of disease activity and similar rates of treatment response. Nonradiographic axial Spondyloarthritis is characterised by a higher prevalence of females and lower percentage of patients with elevated C-reactive protein that might reflect the presence of a certain proportion of patients who develop structural damage in the axial skeleton very slowly or do not develop it at all. Elevated C-reactive protein and active sacroiliitis on magnetic resonance imaging are strongest predictors of structural damage development in the sacroiliac joints and, therefore, of progression from nonradiographic to radiographic stage. The same parameters predict a good clinical response to therapy with tumour necrosis factor alpha blocking agent in axial Spondyloarthritis, but especially if used in nonradiographic disease. SUMMARY: Currently available data support the concept of axial Spondyloarthritis as one entity. Nonradiographic axial Spondyloarthritis seems to be, however, more heterogeneous than ankylosing spondylitis because of the presence of patients with a self-limiting disease or a slow disease course.
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rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial Spondyloarthritis
Annals of the Rheumatic Diseases, 2011Co-Authors: Denis Poddubnyy, H Haibel, J Listing, Elisabeth Markerhermann, Henning Zeidler, Jurgen Braun, Martin Rudwaleit, Joachim SieperAbstract:Objective To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial Spondyloarthritis over a period of 2 years and to explore predictors of progression. Methods 210 patients with axial Spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data. Results 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial Spondyloarthritis. More patients with non-radiographic Spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated ‘true’ progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial Spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial Spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p Conclusion Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial Spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.
Matthew A Brown - One of the best experts on this subject based on the ideXlab platform.
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Does the microbiome play a causal role in Spondyloarthritis?
Clinical Rheumatology, 2014Co-Authors: James T. Rosenbaum, Mark Asquith, Phoebe Lin, Mary-ellen Costello, Tony J. Kenna, Matthew A BrownAbstract:The purpose of this study is to review the potential causal role of the microbiome in the pathogenesis of Spondyloarthritis. The method used for the study is literature review. The microbiome plays a major role in educating the immune response. The microbiome is strongly implicated in inflammatory bowel disease which has clinical and genetic overlap with Spondyloarthritis. The microbiome also plays a causal role in bowel and joint disease in HLA B27/human beta 2 microglobulin transgenic rats. The mechanism(s) by which HLA B27 could influence the microbiome is unknown but theories include an immune response gene selectivity, an effect on dendritic cell function, or a mucosal immunodeficiency. Bacteria are strongly implicated in the pathogenesis of Spondyloarthritis. Studies to understand how HLA B27 affects bacterial ecosystems should be encouraged.
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The window of opportunity: a relevant concept for axial Spondyloarthritis
Arthritis Research & Therapy, 2014Co-Authors: Philip C Robinson, Matthew A BrownAbstract:The window of opportunity is a concept critical to rheumatoid arthritis treatment. Early treatment changes the outcome of rheumatoid arthritis treatment, in that response rates are higher with earlier disease-modifying anti-rheumatic drug treatment and damage is substantially reduced. Axial Spondyloarthritis is an inflammatory axial disease encompassing both nonradiographic axial Spondyloarthritis and established ankylosing spondylitis. In axial Spondyloarthritis, studies of magnetic resonance imaging as well as tumor necrosis factor inhibitor treatment and withdrawal studies all suggest that early effective suppression of inflammation has the potential to reduce radiographic damage. This potential would suggest that the concept of a window of opportunity is relevant not only to rheumatoid arthritis but also to axial Spondyloarthritis. The challenge now remains to identify high-risk patients early and to commence treatment without delay. Developments in risk stratification include new classification criteria, identification of clinical risk factors, biomarkers, genetic associations, potential antibody associations and an ankylosing spondylitis-specific microbiome signature. Further research needs to focus on the evidence for early intervention and the early identification of high-risk individuals.
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axial Spondyloarthritis a new disease entity not necessarily early ankylosing spondylitis
Institute of Health and Biomedical Innovation, 2013Co-Authors: Philip C Robinson, B P Wordsworth, John D Reveille, Matthew A BrownAbstract:New classification criteria for axial Spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory Spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial Spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.
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The genetics of ankylosing spondylitis and axial Spondyloarthritis.
Rheumatic diseases clinics of North America, 2012Co-Authors: Philip C Robinson, Matthew A BrownAbstract:Ankylosing spondylitis (AS) and Spondyloarthritis are strongly genetically determined. The long-standing association with HLA-B27 is well described, although the mechanism by which that association induces AS remains uncertain. Recent developments include the description of HLA-B27 tag single nucleotide polymorphisms in European and Asian populations. An increasing number of non-MHC genetic associations have been reported, which provided amongst other things the first evidence of the involvement of the IL-23 pathway in AS. The association with ERAP1 is now known to be restricted to HLA-B27 positive disease. Preliminary studies on the genetics of axial Spondyloarthritis demonstrate a lower HLA-B27 carriage rate compared with AS. Studies with larger samples and including non-European ethnic groups are likely to further advance the understanding of the genetics of AS and Spondyloarthritis.
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Role of NOD2 variants in spondylarthritis.
Arthritis & Rheumatism, 2002Co-Authors: A. M. Crane, Linda A. Bradbury, David A. Van Heel, Dermot P.b. Mcgovern, Sinead Brophy, Laurence A. Rubin, Katherine A. Siminovitch, B. Paul Wordsworth, Andrei Calin, Matthew A BrownAbstract:Objective. To investigate the role of the gene NOD2 in susceptibility to, and clinical manifestations of, ankylosing spondylitis (AS). Methods. A case-control study of NOD2 polymorphisms known to be associated with Crohn's disease (CD) (Pro(268)Ser, Arg(702)Trp, Gly(908)Arg, and Len(1007)fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls. Associations between NOD2 polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated. Exclusion linkage mapping of chromosome 16 was performed in a separate group of 185 multicase families with AS. Results. An association was identified between Gly(908)Arg and UC spondylarthritis (P = 0.016, odds ratio [OR] 4.6, 95% confidence interval [95% CI] 1.3-16), and a nonsignificant trend with a similar magnitude was observed in association with CD spondylarthritis (P = 0.08, OR 3.9, 95% CI 0.8-18). The Pro(268)Ser variant was inversely associated with UC spondylarthritis (P = 0.003, OR 0.55, 95% CI 0.37-0.82), but not with CD spondylarthritis. No association was demonstrated between NOD2 variants and primary AS, or between other variants of NOD2 and either UC or CD spondylarthritis. Carriage of the Pro(218)Ser polymorphism was associated with greater disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = 0.002). Although patients with CD had a younger age at spondylarthritis onset than did those with UC (22.4 years versus 26.4 years; P = 0.01), no association was noted between the NOD2 variants linked with CD and age at spondylarthritis onset. In primary AS, the presence of a gene with a magnitude of association >2.0 was excluded (exclusion logarithm of odds score less than -2.0), and no association was observed with the microsatellite D16S3136. Conclusion. NOD2 variants do not significantly affect the risk of developing primary AS, but may influence susceptibility to, and clinical manifestations of, colitic spondylarthritis.
