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Smolen J.S.,Medical University of Vienna | Smolen J.S.,Hietzing Hospital Vienna | Braun J.,Rheumazentrum Ruhrgebiet | Dougados M.,University of Paris Descartes | And 30 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). Objective To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. Methods Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. Results Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. Conclusions The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.


Landewe R.,Atrium Medical | Braun J.,Rheumazentrum Ruhrgebiet | Deodhar A.,Oregon Health And Science University | Dougados M.,Cochin Hospital | And 11 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Objectives To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPIDaxSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA). Methods Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. Results Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. Conclusions CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.


Hermann K.-G.A.,Charite University Hospital | Baraliakos X.,Rheumazentrum Ruhrgebiet | Van Der Heijde D.M.F.M.,Leiden University | Jurik A.-G.,Aarhus University Hospital | And 8 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: The aim of this study was to define characteristic MRI findings in the spine of patients with axial spondyloarthritis (SpA) and provide a definition of a positive spinal MRI for inflammation and structural changes. Methods: Technical details of spinal MRI and the description of spinal lesions of both inflammation and structural changes were discussed in consecutive meetings of 10 experts of the Assessment in SpondyloArthritis international Society (ASAS). The discussions aimed at a broad consensus on definitions of 'a positive spinal MRI' for both types of lesions and were backed up by a systematic literature search. Results: A total of six different types of lesions were described for inflammation - anterior/posterior spondylitis, spondylodiscitis, arthritis of costovertebral joints, arthritis of zygoapophyseal joints and enthesitis of spinal ligaments - and another four for structural changes - fatty deposition, erosions, syndesmophytes and ankylosis. In the literature review, four relevant papers were identified. Anterior/posterior spondylitis and fat depositions at vertebral edges were considered as the most typical findings in SpA. Based on expert consensus and taking the literature review into consideration, a positive spinal MRI for inflammation was defined as the presence of anterior/posterior spondylitis in ≥3 sites. Evidence of fatty deposition at several vertebral corners was found to be suggestive of axial SpA, especially in younger adults. ASAS members (n=56) approved these definitions by voting in January 2010. Conclusions: This consensus statement gives clear descriptions of disease-related spinal lesions and of definitions of a positive spinal MRI for inflammatory lesions (spondylitis) and structural changes (fat deposition). These definitions can be used to describe findings of spinal MRI in patients with SpA in daily practice and clinical studies.


Molto A.,University of Paris Descartes | Molto A.,Autonomous University of Barcelona | Paternotte S.,University of Paris Descartes | van der Heijde D.,Leiden University | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background: The Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis (SpA) allows classification of patients with ('imaging' arm) and without ('clinical' arm) imaging abnormalities of the sacroiliac joints. Objective: To compare the phenotype of early axial SpA with regard to the two arms of the ASAS axial SpA criteria. Methods: Demographics, clinical and biological features of SpA, disease activity, severity parameters, and imaging abnormalities at the sacroiliac and spine levels were compared, in the two arms of the ASAS axial SpA criteria, in the patients of the French cohort of early SpA. Results: Of the 615 patients analysed, 435 (70.7%) met the ASAS criteria (262 (60.2%) and 173 (39.8%) in the imaging and clinical arms, respectively). There were no major differences in the characteristics of the two groups except that those in the imaging arm were more likely to be younger, male and have higher concentrations of C-reactive protein. Imaging abnormalities other than those meeting the ASAS criteria for the imaging arm (ie, x-ray-determined structural damage or MRI-revealed inflammatory changes in the sacroiliac joint (SIJ)) were observed (MRI-SIJ structural damage (55.0% vs 3.5%), MRI-spine inflammatory changes (35.1% vs 12.9%), MRI-spine structural damage (10.3% vs 5.3%) and x-ray-syndesmophytes (11.8% vs 5.3%)) in the imaging versus clinical arm, respectively. Conclusions: Our study confirms the external validity of the clinical arm of the ASAS criteria. It is notable that many patients in the clinical arm showed other imaging changes in SIJs and spine. © 2014 BMJ Publishing Group Ltd & European League Against Rheumatism.


Rudwaleit M.,Endokrinologikum Berlin | Marker-Hermann E.,HSK Dr. Horst Schmidt Kliniken GmbH
Zeitschrift fur Rheumatologie | Year: 2012

Low back pain is a frequent health problem and causes substantial costs. Between 2007 and 2010 a panel of interdisciplinary experts in Germany developed evidence-based national guidelines for the management of nonspecific low back pain. These guidelines cover diagnosis (red flags and yellow flags), treatment recommendations and health care algorithms. In acute nonspecific low back pain diagnostic imaging is not indicated and should be avoided. Education and patient information, maintenance of routine daily physical activities and pain therapy as needed are the cornerstones of acute nonspecific low back pain therapy. In order to prevent the development of chronic back pain in patients with acute nonspecific back pain, the early identification of parameters predictive of a high risk of chronicity (yellow flags) is of particular importance even in primary care. © Springer-Verlag 2012.


Poddubnyy D.,Charité - Medical University of Berlin | Rudwaleit M.,Endokrinologikum Berlin | Sieper J.,Charité - Medical University of Berlin
Zeitschrift fur Rheumatologie | Year: 2012

The diagnosis of axial spondyloarthritis (SpA) or ankylosing spondylitis (AS) is often delayed by 5-10 years after the first symptoms have appeared. In order to improve the earlydiagnosis of SpA an evidenced-based algorithm including clinical, laboratory and imaging parameters was developed. Moreover, the recently published ASAS criteria for axial and peripheral SpA should give rheumatologists more confidence in making the diagnosis of SpA and provide further support for the SpA concept. Furthermore, an easy strategy for the recognition of patients with a high probability of AS/SpA on the primarycare level has been developed and recentlyvalidated.


Poddubnyy D.,Charité - Medical University of Berlin | Conrad K.,Charité - Medical University of Berlin | Haibel H.,Charité - Medical University of Berlin | Syrbe U.,Charité - Medical University of Berlin | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To investigate the role of serum vascular endothelial growth factor (VEGF) as a predictor of radiographic spinal progression in patients with axial spondyloarthritis (axSpA). Methods: Altogether, 172 patients with definite axSpA (95 with ankylosing spondylitis and 77 with non-radiographic axSpA) were included in this study. Spinal radiographs obtained at baseline and after 2 years of follow-up were scored independently by two trained readers in a concealed and randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) scoring system and for the presence of syndesmophytes. Radiographic spinal progression after 2 years was defined as (1) mSASSS worsening by ≥2 units, and (2) new syndesmophyte formation or formation of a bridging syndesmophyte from two single syndesmophytes. Serum VEGF levels were detected at baseline. Results: Mean baseline VEGF values were significantly higher in patients with mSASSS worsening by ≥2 units after 2 years (n=22) than in those without progression (562±357 vs 402±309 pg/mL, respectively, p=0.027) and in patients with syndesmophyte formation (n=18) again as compared with those without new bone formation (579±386 vs 404±307 pg/mL, respectively, p=0.041). VEGF as a predictor of radiographic spinal progression performed especially well in patients who were already at high risk for such a progression due to the presence of syndesmophytes at baseline (n=48). In these patients, a VEGF serum level of >600 pg/mL had a sensitivity of 53%, a specificity of 97% and an OR=36.6 (95% CI 3.9 to 341.5) as a predictor of mSASSS worsening by ≥2 units. For syndesmophyte formation, elevated VEGF demonstrated a sensitivity of 47%, a specificity of 94% and an OR=13.6 (95% CI 2.4 to 78.3). Conclusions: An elevated serum level of VEGF (>600 pg/mL) is highly specific as a predictor of radiographic spinal progression in patients with axSpA, especially in patients who are at high risk for further progression due to the presence of syndesmophytes. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.


Poddubnyy D.,Charité - Medical University of Berlin | Rudwaleit M.,Endokrinologikum Berlin
Expert Opinion on Biological Therapy | Year: 2013

Introduction: Following its marketing authorization for the treatment of ankylosing spondylitis (AS) in 2006 in the United States und in the European Union, adalimumab became one of the most frequently prescribed tumor necrosis factor (TNF) α blockers available for this indication. Recently, the label for adalimumab was extended to nonradiographic axial spondyloarthritis (nr-axSpA), which might be considered as an early stage of AS. The increasing number of patients with AS being treated with adalimumab raises issues concerning long-term safety, efficacy in the prevention of structural damage in the spine and high treatment costs. Areas covered: Herein, we summarize data on efficacy and safety of adalimumab treatment in AS and nr-axSpA obtained over the past 5 years. Expert opinion: Adalimumab is clinically effective and reasonably safe in the short-term and long-term treatment of patients with AS who do not respond to standard therapy. Recent data indicate good efficacy of adalimumab also in patients with nr-axSpA but only in the presence of objective signs of active inflammation. Yet unresolved questions relate to the ability of adalimumab to stop or retard structural damage development in the spine in patients with AS and nr-axSpA. The introduction of biosimilar drugs in the near future may potentially reduce the currently very high treatment costs associated with adalimumab treatment. © 2013 Informa UK, Ltd.


Poddubnyy D.,Charité - Medical University of Berlin | Brandt H.,Charité - Medical University of Berlin | Vahldiek J.,Charité - Medical University of Berlin | Spiller I.,Charité - Medical University of Berlin | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2012

Objective: This study was aimed at investigating the frequencies of non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) diagnoses and their ratios in relation to symptom duration in patients referred because of chronic back pain and suspicion of axial SpA. Methods: In this monocentre study, orthopaedists and primary care physicians were requested to refer patients with chronic low back pain (duration >3 months) and onset of back pain before 45 years of age to a SpA-specialised rheumatology outpatient clinic for further diagnostic investigation, if proposed screening parameters were present. The ratio of nr-axSpA to AS was analysed in relation to the duration of symptoms. Results: A diagnosis of definite axial SpA was made in 43.7% of the referred patients (n=522). Axial SpA was diagnosed in a similar percentage of about 50% if back pain duration was <9 years but decreased to 36% if symptom duration was >9 years. Nr-axSpA represented the majority of patients (67.3%) only if duration of back pain was 1 year and less at the time of referral. Between 1 and 6 years of back pain duration the probability of nr-axSpA and AS was nearly equal (1-3 years: 52.5% and 47.5%, respectively; 3-6 years: 53.7% and 46.3%, respectively). In patients with back pain duration of 6-9 years, AS was more likely (61.1%) to be diagnosed than nr-axSpA (38.9%), and this increased further over time. Conclusions: Non-radiographic axial SpA represents an important differential diagnosis of back pain, especially in patients with recent symptom onset.


Rudwaleit M.,Endokrinologikum Berlin | Sieper J.,Franklin University
Nature Reviews Rheumatology | Year: 2012

The spectrum of HLA-B27-associated inflammatory spine diseases is referred to as axial spondyloarthritis (axSpA). AxSpA encompasses established ankylosing spondylitis (AS) but also nonradiographic axSpA, and can be classified according to the Assessment of SpondyloArthritis international Society classification criteria for axSpA. Specific and effective therapy for axSpA includes education, physiotherapy, NSAIDs and biologic agents, as appropriate. Patients with axSpA, however, are often diagnosed late in the course of the disease. As specific therapy is available, the effective identification of those individuals who are likely to have axSpA among patients with chronic back pain in primary care and their subsequent referral to a rheumatologist for establishing a correct diagnosis is worth pursuing. Candidate referral parameters that can easily be applied to patients with chronic back pain and age at onset ĝ‰ Currency sign45 years (the target population) include inflammatory back pain (IBP) and positivity for HLA-B27. Following diagnostic work-up by a rheumatologist, these referral parameters, either alone or in combination, have led to the diagnosis of as many as 33-45% of patients within this target population with axSpA, 41-62% of whom had undiagnosed AS. Thus, educating primary care physicians on the value of IBP and HLA-B27 testing within this target population, and referral to a rheumatologist if one of these parameters is positive, is a promising approach to reduce the long delay in diagnosing patients with axSpA. © 2012 Macmillan Publishers Limited All rights reserved.

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