X. Baraliakos

2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis

This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made — if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good.

The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis

The field of spondyloarthritis (SpA) has experienced major progress in the last decade, especially with regard to new treatments, earlier diagnosis, imaging technology and a better definition of outcome parameters for clinical trials. In the present work, the Assessment in SpondyloArthritis international Society (ASAS) provides a comprehensive handbook on the most relevant aspects for the assessments of spondyloarthritis, covering classification criteria, MRI and x rays for sacroiliac joints and the spine, a complete set of all measurements relevant for clinical trials and international recommendations for the management of SpA. The handbook focuses at this time on axial SpA, with ankylosing spondylitis (AS) being the prototype disease, for which recent progress has been faster than in peripheral SpA. The target audience includes rheumatologists, trial methodologists and any doctor and/or medical student interested in SpA. The focus of this handbook is on practicality, with many examples of MRI and x ray images, which will help to standardise not only patient care but also the design of clinical studies.

Defining active sacroiliitis on Magnetic Resonance Imaging (MRI) for classification of axial spondyloarthritis –a consensual approach by the ASAS/ OMERACT MRI Group

Background: Magnetic resonance imaging (MRI) of sacroiliac joints has evolved as the most relevant imaging modality for diagnosis and classification of early axial spondyloarthritis (SpA) including early ankylosing spondylitis. Objectives: To identify and describe MRI findings in sacroiliitis and to reach consensus on which MRI findings are essential for the definition of sacroiliitis. Methods: Ten doctors (two radiologists and eight rheumatologists) from the ASAS/OMERACT MRI working group reviewed and discussed in three workshops MR images depicting sacroiliitis associated with SpA and other conditions which may mimic SpA. Descriptions of the pathological findings and technical requirements for the appropriate acquisition were formulated. In a consensual approach MRI findings considered to be essential for sacroiliitis were defined. Results: Active inflammatory lesions such as bone marrow oedema (BMO)/osteitis, synovitis, enthesitis and capsulitis associated with SpA can be detected by MRI. Among these, the clear presence of BMO/osteitis was considered essential for defining active sacroiliitis. Structural damage lesions such as sclerosis, erosions, fat deposition and ankylosis can also be detected by MRI. At present, however, the exact place of structural damage lesions for diagnosis and classification is less clear, particularly if these findings are minor. The ASAS group formally approved these proposals by voting at the annual assembly. Conclusions: For the first time, MRI findings relevant for sacroiliitis have been defined by consensus by a group of rheumatologists and radiologists. These definitions should help in applying correctly the imaging feature “active sacroiliitis by MRI” in the new ASAS classification criteria for axial SpA.

Progression of radiographic damage in patients with ankylosing spondylitis - Defining the central role of syndesmophytes

Background: Structural changes such as erosions, syndesmophytes and ankylosis are characteristic of ankylosing spondylitis (AS). These can be quantified by the modified Stokes Anklylosing Spondylitis Spinal Score (mSASSS). It is unknown which radiographic feature is most relevant for the assessment of change and the prediction of future damage in AS. Objectives: To analyse radiographic progression in AS by using different assessments to define the most important changes. Methods: Spinal radiographs of 116 patients with AS were scored by the mSASSS at baseline (BL) and after 2 years. Radiographic progression was assessed by differentiating (1) any change; (2) progression to syndesmophytes/ankylosis (definite change); and (3) changes exceeding the smallest detectable change (SDC) as predefined. A growth angle of 45° was used to differentiate syndesmophytes from spondylophytes. Results: Some radiographic progression after 2 years was detected in 42% of patients, novel syndesmophytes in 31% of patients, and, using the SDC (calculated at 2 mSASSS units) as cut-off, progression was seen in 28% of patients. Thus, in 74% of the patients changes were because of syndesmophytes and/or ankylosis. Using the predefined cut-off, only 12% of all syndesmophytes were spondylophytes. Patients with such changes were of older age. Definite radiographic progression was found in 44% of the patients with syndesmophytes/ankylosis at BL (nu200a=u200a57) versus 19% (pu200a=u200a0.03) of the patients without such changes (nu200a=u200a59). Conclusions: Syndesmophytes and ankylosis are the most relevant structural changes in AS, and also in the mSASSS. Development of just one syndesmophyte within 2 years indicates progression of structural changes in AS; this is relevant for clinical practice. Syndesmophytes are the best predictors of radiographic progression.

Inflammation in ankylosing spondylitis: a systematic description of the extent and frequency of acute spinal changes using magnetic resonance imaging

Background: Magnetic resonance imaging (MRI) is increasingly used to detect inflammation in the spine of patients with ankylosing spondylitis (AS). Objectives: To detect differentially the presence and extent of inflammation in the three spinal segments of patients with AS by MRI. Methods: In 38 patients with active AS, acute spinal lesions were assessed by T1 weighted, gadolinium enhanced, spin echo MRI (T1/Gd-DTPA) and short τ inversion recovery (STIR) sequences. MRI was quantified by the validated scoring system ASspiMRI-a. Acute spinal lesions were detected in the whole spine and in each spinal segment. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. Results: A greater number of inflammatory spinal lesions were found by the STIR sequence than by Gd-DTPA: inflammation was present in 30.6% of the VUs as assessed by STIR, compared with 26.8% of the same VUs assessed by T1/Gd-DTPA. Inflammation was found more commonly in the thoracic spine (TS) than in the cervical (CS) or the lumbar spine (LS) with both techniques. When STIR was used, spinal inflammation in the CS, the TS, and LS was detected in 10/38 (26%), 28/38 (74%), and 9/38 (24%) patients, respectively. The VU T7/8 was found to be the VU most often affected by both techniques (27.8% by T1/Gd-DTPA and 34.5% by STIR). Conclusions: Spinal inflammation is a common manifestation in patients with AS, and appears more frequently in the TS. The scoring system ASspiMRI-a can be used for evaluation of acute spinal changes in AS.

EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice

A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9–9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.

Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis

OBJECTIVEnTo perform a literature review as basis for the update of the Assessment in SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) treatment recommendations with biologics in AS.nnnMETHODSnA literature search of all publications found in MedLine, Embase and Cochrane database between 2005 and 2009 and in the EULAR/ACR meetings between 2007 and 2009 was performed. The research evidence and strength of recommendation (SOR) for biologics were provided.nnnRESULTSnOut of 247 reports on AS treatment with biologics, 98 contained efficacy data and 25 had complete data for analysis. The treatment effect sizes (95% CI) for anti-TNF vs placebo varied between 0.34 (0.08, 0.6) and 1.5 (0.45, 2.5) for BASDAI and 0.33 (0.07, 0.59) and 2.5 (1.3, 3.7) for BASFI. The calculation of the numbers needed to treat all the different outcomes varied between 2.3 and 3.0 patients for all ASAS outcomes and between 2.7 and 6.5 patients for ASAS partial remission. Data on biologics other than anti-TNF and for TNF blockers on juvenile SpA were limited. The incidence rates of uveitis during anti-TNF treatment varied between 4.4/100 patient-years (pys) and 15.6/100u2009pys during placebo (Pu2009<u20090.05). The incidence rates of IBD flares were significantly less during infliximab treatment (0.2/100u2009pys). The rate of infections was higher in patients treated with anti-TNF as compared with placebo, but there was no difference in the incidence of serious infections for treatment with anti-TNF vs placebo.nnnCONCLUSIONSnThe overall evidence was very high for anti-TNF treatment (1b, SOR: A) with respect to efficacy and safety, while it was low for biologic treatment other than anti-TNF (3, SOR: C).

LONG TERM INHIBITION OF IL-17A WITH SECUKINUMAB REDUCES SPINAL INFLAMMATION BUT HAS NO INFLUENCE ON FATTY LESIONS AS ASSESSED BY MAGNETIC RESONANCE IMAGING IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Background Secukinumab (fully human IgG1k anti-IL17A monoclonal antibody) significantly improved clinical signs and symptoms of active ankylosing spondylitis (AS) patients enrolled in a recent proof-of-concept (PoC) study. Magnetic resonance images (MRI) of these patients (pts) showed reduction of spinal inflammation at week (W) 6 and W28 after initiation of treatment. Objectives To evaluate a subgroup of pts (N=13) in the open label extension study, who had MRI assessments at baseline (BL), W28 and W94. Methods In the 28W PoC study, 27/30 pts had sequential MRI studies, 22 had received secukinumab 2x10 mg/kg administered intravenously 3 Ws apart, and 5 pts had been randomised to placebo. 20 patients entered the extension study, 13 having MRI data at W94. Of these 13, ten were treated with secukinumab and 3 with placebo in the core study. In the extension study, all received secukinumab 14x3 mg/kg administered 4 Ws apart. MRIs (T1 and STIR) were rescored for this study. ASspiMRI-a scores and the occurrence of vertebral edges (VE) inflammatory and fatty lesions were evaluated by an independent blinded reader. Results All 13 pts completed this exploratory MRI substudy. In pts receiving 2x10 mg/kg secukinumab followed by 14x3 mg/kg (n=10) secukinumab, spinal inflammation was reduced compared to BL at W28 –similar to the results of the core study– and this reduction was sustained up to W94 (Fig 1). Also in 3 pts who had initially received placebo switching to secukinumab at W28, MRI inflammation at W94 was reduced. Of the 920 VEs evaluated, the proportion of VEs with inflammatory lesions was reduced from 9.9% (n=91) at BL to 3.7% (n=34) at W28 and 3.6% (n=33) at W94. In contrast, the proportion of fatty lesions at BL (13.5%, n=124) remained largely unchanged at W28 (14.3%, n=132) and W94 (13.7%, n=126). Image/graph Conclusions MRI analysis suggests that the IL-17 inhibitor secukinumab may reduce spinal inflammation and this effect may be sustained for up to 2 years, using a lower maintenance dose compared to the induction regimen. Notably, secukinumab appeared not to have any influence on fatty lesions. This observation contrasts recent reports of AS pts treated with TNF-blockers. The potential impact of these preliminary findings on radiographic progression under secukinumab therapy will be studied in larger trials. Disclosure of Interest X. Baraliakos: None Declared, J. Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Consultant for: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB, D. Laurent Shareholder of: Novartis, Employee of: Novartis, D. Baeten Grant/research support from: Abbott, MSD, Pfizer, Centocor, Jansen, Novartis, UCB, Eli Lilly, Boehringer, Roche, BMS., Consultant for: Abbott, MSD, Pfizer, Centocor, Jansen, Novartis, UCB, Eli Lilly, Boehringer, Roche, BMS., D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli-Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Vertex, Employee of: Director of Imaging Rheumatology bv, J. Sieper Consultant for: Novartis, P. Emery: None Declared, I. McInnes Consultant for: Novartis, J. van Laar: None Declared, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Rhoche, Schering-Plough, UCB, Wyeth, Consultant for: Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, Glaxo-Smith-Kline, Novartis, Merck, Pfizer, Rhoche, Schering-Plough, UCB, Wyeth, Employee of: director of Rheumatology Consultancy BV, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Rhoche, Schering-Plough, UCB, Wyeth, P. Wordsworth: None Declared, J. Wollenhaupt: None Declared, H. Kellner: None Declared, A. Wright Shareholder of: Novartis, Employee of: Novartis, F. Vandenhende: None Declared, K. Radford Employee of: Novartis contractor, B. Borah Employee of: Novartis, W. Hueber Shareholder of: Novartis, Employee of: Novartis

[German translation and cross-cultural adaptation of the ASAS health index : An ICF-based instrument for documentation of functional ability in patients with ankylosing spondylitis].

ZusammenfassungDie Erfassung des Schweregrades der Erkrankung von Patienten mit Spondyloarthritis (SpA) kann eine klinische Herausforderung darstellen, zumal der Verlauf der SpA sehr unterschiedlich sein kann. Patienten mit SpA klagen häufig über Symptome wie Schmerzen, Müdigkeit und Steifigkeit, aber auch über Einschränkungen psychischer Funktionen und der sozialen Partizipation. Diese große Bandbreite an Funktionsminderungen konnte bislang nur unzureichend und nicht mit nur einem Messinstrument erfasst werden. Trotz verschiedener Versuche haben sich Experten in den letzten Jahren nicht auf eine Definition des Schweregrades und der Erfassung des Ausmaßes des Schweregrades einigen können. Dies war der Ausgangspunkt für die Entwicklung des hier vorgestellten ASAS-Gesundheitsindex, initial noch fokussiert auf Patienten mit ankylosierender Spondylitis (AS). Dieser Fragebogen dient der Erfassung von Gesundheit und Funktionsfähigkeit bei Patienten mit AS und liegt zusammen mit dem begleitenden Umfeldfaktorenset seit 2015 als englischsprachige Originalversion ASAS-Gesundheitsindex vor. In der hier vorliegenden Arbeit werden die Übersetzung ins Deutsche und die transkulturelle Adaptation des ASAS-Gesundheitsindex und des begleitenden Umfeldfaktorensets beschrieben.AbstractDocumentation of the severity of the disease in patients with spondyloarthritis (SpA) can represent a clinical challenge, especially as the course of SpA can be very different. Patients with SpA often complain of symptoms, such as pain, fatigue and stiffness as well as limitations in mental functions and social participation. This wide range of functional impairments could so far only be insufficiently documented and not with one single measurement instrument. Despite various attempts in recent years, experts could not reach agreement on a definition of the severity and documentation of the extent of the severity. This was the starting point for the development of the ASAS health index presented here, which initially focused on patients with ankylosing spondylitis (AS). This questionnaire serves to document the health and functional ability of patients with AS and has been available since 2015 as the original english version of the ASAS health index together with the accompanying environmental factors set. This article describes the German translation and transcultural adaptation of the ASAS health index and the accompanying environmental factors set.

Deutsche Übersetzung und krosskulturelle Adaptation des ASAS-Gesundheitsindex

ZusammenfassungDie Erfassung des Schweregrades der Erkrankung von Patienten mit Spondyloarthritis (SpA) kann eine klinische Herausforderung darstellen, zumal der Verlauf der SpA sehr unterschiedlich sein kann. Patienten mit SpA klagen häufig über Symptome wie Schmerzen, Müdigkeit und Steifigkeit, aber auch über Einschränkungen psychischer Funktionen und der sozialen Partizipation. Diese große Bandbreite an Funktionsminderungen konnte bislang nur unzureichend und nicht mit nur einem Messinstrument erfasst werden. Trotz verschiedener Versuche haben sich Experten in den letzten Jahren nicht auf eine Definition des Schweregrades und der Erfassung des Ausmaßes des Schweregrades einigen können. Dies war der Ausgangspunkt für die Entwicklung des hier vorgestellten ASAS-Gesundheitsindex, initial noch fokussiert auf Patienten mit ankylosierender Spondylitis (AS). Dieser Fragebogen dient der Erfassung von Gesundheit und Funktionsfähigkeit bei Patienten mit AS und liegt zusammen mit dem begleitenden Umfeldfaktorenset seit 2015 als englischsprachige Originalversion ASAS-Gesundheitsindex vor. In der hier vorliegenden Arbeit werden die Übersetzung ins Deutsche und die transkulturelle Adaptation des ASAS-Gesundheitsindex und des begleitenden Umfeldfaktorensets beschrieben.AbstractDocumentation of the severity of the disease in patients with spondyloarthritis (SpA) can represent a clinical challenge, especially as the course of SpA can be very different. Patients with SpA often complain of symptoms, such as pain, fatigue and stiffness as well as limitations in mental functions and social participation. This wide range of functional impairments could so far only be insufficiently documented and not with one single measurement instrument. Despite various attempts in recent years, experts could not reach agreement on a definition of the severity and documentation of the extent of the severity. This was the starting point for the development of the ASAS health index presented here, which initially focused on patients with ankylosing spondylitis (AS). This questionnaire serves to document the health and functional ability of patients with AS and has been available since 2015 as the original english version of the ASAS health index together with the accompanying environmental factors set. This article describes the German translation and transcultural adaptation of the ASAS health index and the accompanying environmental factors set.