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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, R Landewe, Philip J Mease, Filip Van Den Bosch, 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, M Dougados, Jurgen Braun, 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, M Dougados, Jurgen Braun, 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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baseline radiographic damage elevated acute phase reactant levels and cigarette smoking status predict spinal radiographic progression in early axial Spondylarthritis
Arthritis & Rheumatism, 2012Co-Authors: Denis Poddubnyy, H Haibel, J Listing, Elisabeth Markerhermann, Jurgen Braun, Joachim Sieper, H Zeidler, M RudwaleitAbstract:Objective To assess prospectively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial Spondylarthritis (SpA). Methods Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup. Spinal radiographs were scored by 2 trained readers in a blinded, randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Spinal radiographic progression was defined as worsening of the mean mSASSS by ≥2 units over 2 years. Results Among the patients with axial SpA, 14.3% showed spinal radiographic progression after 2 years (20% of those with AS and 7.4% of those with nonradiographic axial SpA). The following parameters were independently associated with spinal radiographic progression: presence of syndesmophytes at baseline (odds ratio [OR] 6.29, P < 0.001), elevated levels of markers of systemic inflammation (for the erythrocyte sedimentation rate, OR 4.04, P = 0.001; for C-reactive protein level time-averaged over 2 years, OR 3.81, P = 0.001), and cigarette smoking (OR 2.75, P = 0.012). These associations were confirmed by multivariate logistic regression analysis. No clear association with spinal radiographic progression was observed for HLA–B27 status, sex, age, disease duration, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, presence of peripheral arthritis, enthesitis, psoriasis, treatment with nonsteroidal antiinflammatory drugs, or treatment with disease-modifying antirheumatic drugs at baseline. Conclusion The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.
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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, M Rudwaleit, H Haibel, J Listing, Elisabeth Markerhermann, Henning Zeidler, Jurgen Braun, 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.
Walter P. Maksymowych - One of the best experts on this subject based on the ideXlab platform.
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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, R Landewe, Philip J Mease, Filip Van Den Bosch, 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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Imaging in Spondyloarthritis: Controversies in Recognition of Early Disease
Current rheumatology reports, 2016Co-Authors: Ulrich Weber, Anne Grethe Jurik, Robert G. Lambert, Walter P. MaksymowychAbstract:Advanced imaging has become essential for recognition of clinically suspected early spondyloarthritis. This report summarizes recent progress towards a data-driven comprehensive definition of a positive sacroiliac joint MRI in axial spondyloarthritis, which incorporates contextual information provided by structural lesions alongside with active changes. A focus is on emerging limitations and challenges with increasing use of imaging in spondyloarthritis. We discuss the ongoing controversy as to whether sacroiliac joint MRI due to its superior reliability and ability to depict both structural and active lesions should be the preferred imaging modality in early disease over the traditional approach with pelvic radiographs. Another challenge is transferring the expanding knowledge about imaging evaluation in spondyloarthritis to the community of rheumatologists and radiologists. Advanced imaging modalities will not become the gold standard for diagnosis of spondyloarthritis, which remains a process of composite deduction based on complementary information obtained from clinical, laboratory, and imaging assessment.
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Treatment recommendations for the management of axial spondyloarthritis.
The American journal of the medical sciences, 2013Co-Authors: M E Beth Smith, Atul Deodhar, Walter P. MaksymowychAbstract:Abstract Clinical practice guidelines aid clinicians in providing optimal care for their patients. Over the past decade, treatment guidelines have been published for ankylosing spondylitis (AS), but there are no evidence-based recommendations for the management of axial spondyloarthritis. In 2003, Canadian rheumatologists published treatment recommendations for AS, which have been subsequently updated. More recently, in 2011, the Assessment of SpondyloArthritis international Society and the European League Against Rheumatism published recommendations for the management of AS. SPondyloArthritis Research and Treatment Network proposes an American College of Rheumatology–led effort to develop treatment recommendations for axial spondyloarthritis.
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validation of whole body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with Spondylarthritis
Arthritis Care and Research, 2009Co-Authors: U Weber, Walter P. Maksymowych, Anne Grethe Jurik, Christian W A Pfirrmann, Kaspar Rufibach, Rudolf O Kissling, Muhammad Asim Khan, Robert G W Lambert, Juerg HodlerAbstract:Objective To compare the performance of whole-body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active Spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole-body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA. Methods Thirty-two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4) fulfilling the modified New York criteria were scanned by whole-body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web-based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole-body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability. Results The Pearson's correlation coefficients between whole-body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole-body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole-body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole-body MRI for the 3 possible reader pairs. Conclusion Whole-body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.
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progress in Spondylarthritis spondyloarthritis lessons from imaging
Arthritis Research & Therapy, 2009Co-Authors: Walter P. MaksymowychAbstract:The advent of magnetic resonance imaging (MRI) and advanced sonographic techniques has led to a resurgence of interest in the role of imaging in the evaluation and management of spondyloarthritis. Radiography remains the cornerstone of diagnosis although MRI is more sensitive in early stages of the disease. Inflammatory changes in the sacroiliac joints and spine can now be reliably quantified and can also predict the subsequent development of radiographic changes in the corresponding locations. MRI-based scoring systems for inflammation are highly responsive, facilitating proof-of-concept studies of new therapies for spondyloarthritis. Assessment of chronic changes is much less reliable using MRI, while assessment using radiography lacks sensitivity to change. Assessment of disease modification therefore remains a principle challenge in the development of new therapies for ankylosing spondylitis. Ultrasound may be the preferred approach to the assessment of peripheral inflammation, especially enthesitis. Scintigraphy and computed tomography offer few advantages over MRI.
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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baseline radiographic damage elevated acute phase reactant levels and cigarette smoking status predict spinal radiographic progression in early axial Spondylarthritis
Arthritis & Rheumatism, 2012Co-Authors: Denis Poddubnyy, H Haibel, J Listing, Elisabeth Markerhermann, Jurgen Braun, Joachim Sieper, H Zeidler, M RudwaleitAbstract:Objective To assess prospectively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial Spondylarthritis (SpA). Methods Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup. Spinal radiographs were scored by 2 trained readers in a blinded, randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Spinal radiographic progression was defined as worsening of the mean mSASSS by ≥2 units over 2 years. Results Among the patients with axial SpA, 14.3% showed spinal radiographic progression after 2 years (20% of those with AS and 7.4% of those with nonradiographic axial SpA). The following parameters were independently associated with spinal radiographic progression: presence of syndesmophytes at baseline (odds ratio [OR] 6.29, P < 0.001), elevated levels of markers of systemic inflammation (for the erythrocyte sedimentation rate, OR 4.04, P = 0.001; for C-reactive protein level time-averaged over 2 years, OR 3.81, P = 0.001), and cigarette smoking (OR 2.75, P = 0.012). These associations were confirmed by multivariate logistic regression analysis. No clear association with spinal radiographic progression was observed for HLA–B27 status, sex, age, disease duration, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, presence of peripheral arthritis, enthesitis, psoriasis, treatment with nonsteroidal antiinflammatory drugs, or treatment with disease-modifying antirheumatic drugs at baseline. Conclusion The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.
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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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
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Is interleukin-6 an appropriate target to treat spondyloarthritis patients refractory to anti-tnf therapy? A cross-sectional national survey.
Arthritis Research and Therapy, 2012Co-Authors: Fernando Lekpa, Eric Toussirot, Cécile Poulain, Jean Berthelot, Philippe Gaudin, Michel De Bandt, Daniel Wendling, Martin Soubrier, Philippe Goupille, Thao PhamAbstract:ABSTRACT: INTRODUCTION: To evaluate the safety and efficacy of tocilizumab in patients having failed anti-TNFalpha therapy for spondyloarthritis, under real-life conditions. METHODS: French rheumatologists and internal-medicine practitioners registered on the Club Rhumatismes et Inflammations website were asked to report on patients given tocilizumab (4 or 8 mg/Kg) to treat active disease meeting ASAS criteria for axial or peripheral spondyloarthritis, after anti-TNFalpha treatment failure. Safety and efficacy after 3 and 6 months were assessed retrospectively using standardized questionnaires. RESULTS: Data were obtained for 21 patients, 13 with axial spondyloarthritis (46% men; median age, 42 years; disease duration, 11 years; HLA B27-positive, 92.3%) and 8 with peripheral spondyloarthritis (25% men; median age, 40 years; disease duration, 10 years; HLA B27-positive, 62.5%). No patients with axial disease had at least 20 mm decrease in BASDAI neither a BASDAI50 response or major ASDAS improvements after 3 or 6 months; an ASDAS clinically important improvement was noted at month-3 in 5 of 13 patients and at month-6 in 1 of 4 patients. A good DAS28 response was achieved in 4 patients with peripheral disease, including 1 in EULAR remission at month-3. At month-6, 4 patients were still taking tocilizumab including 1 in EULAR remission and 1 with a good DAS28 response. Tocilizumab was well tolerated, with no serious adverse events. Initially elevated acute-phase reactants declined during tocilizumab therapy. CONCLUSION: In patients having failed anti-TNFtherapy, tocilizumab decreased acute-phase reactants but failed to substantially improve axial spondyloarthritis and was inconsistently effective in peripheral spondyloarthritis.