Showing papers by "Herman Mielants published in 2009"

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection

Abstract: Objective: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). Methods: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (⩾3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. Results: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having “non-radiographic” axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature (“imaging arm”) or the presence of HLA-B27 plus at least two SpA features (“clinical arm”). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). Conclusion: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. Trial registration number: NCT00328068.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal

Abstract: Objective: Non-radiographic axial spondyloarthritis (SpA) is characterised by a lack of definitive radiographic sacroiliitis and is considered an early stage of ankylosing spondylitis. The objective of this study was to develop candidate classification criteria for axial SpA that include patients with but also without radiographic sacroiliitis. Methods: Seventy-one patients with possible axial SpA, most of whom were lacking definite radiographic sacroiliitis, were reviewed as “paper patients” by 20 experts from the Assessment of SpondyloArthritis international Society (ASAS). Unequivocally classifiable patients were identified based on the aggregate expert opinion in conjunction with the expert-reported level of certainty of their judgement. Draft criteria for axial SpA were formulated and tested using classifiable patients. Results: Active sacroiliitis on magnetic resonance imaging (MRI) (odds ratio 45, 95% CI 5.3 to 383; p x rays in conjunction with one SpA feature or, if sacroilitiis is absent, in the presence of at least three SpA features. In a second set of candidate criteria, inflammatory back pain is obligatory in the clinical arm (sensitivity 86.1%; specificity 94.7%). Conclusion: The ASAS group has developed candidate criteria for the classification of axial SpA that include patients without radiographic sacroiliitis. The candidate criteria need to be validated in an independent international study.

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)

Abstract: Objective: Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Methods: Rheumatologists (n = 13) who are experts in SpA took part in a 2-day international workshop to investigate 20 patients with back pain and possible SpA. Each expert documented the presence/absence of clinical parameters typical for IBP, and judged whether IBP was considered present or absent based on the received information. This expert judgement was used as the dependent variable in a logistic regression analysis in order to identify those individual IBP parameters that contributed best to a diagnosis of IBP. The new set of IBP criteria was validated in a separate cohort of patients (n = 648). Results: Five parameters best explained IBP according to the experts. These were: (1) improvement with exercise (odds ratio (OR) 23.1); (2) pain at night (OR 20.4); (3) insidious onset (OR 12.7); (4) age at onset Conclusion: This new approach with real patients defines a set of IBP definition criteria using overall expert judgement on IBP as the gold standard. The IBP experts’ criteria are robust, easy to apply and have good face validity.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative

Abstract: Objectives: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. Methods: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. Conclusions: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine

Abstract: Aim: To study the relationship between disease activity, radiographic damage and physical function in patients with ankylosing spondylitis (AS) Patients and methods: Baseline and 2-year data of the Outcome in Ankylosing Spondylitis International Study (OASIS)(217 patients) were used. Physical function was expressed by the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Dougados Functional Index (DFI); disease activity by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and by erythrocyte sedimentation rate and C-reactive protein; and structural damage by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Syndesmophyte- and non-syndesmophyte sum cores, and numbers of affected (bridged) vertebral units were derived from the mSASSS. Univariate correlations were calculated on baseline values using the Spearman rank correlation. Multivariate associations were investigated by generalised estimating equations (GEE) on baseline and 2-year data. Results: mSASSS correlated moderately well with BASFI (Spearman’s r = 0.45) and DFI (r = 0.38). BASDAI correlated well with BASFI (r = 0.66) and DFI (r = 0.59). Correlation coefficients for mSASSS versus BASFI and DFI decreased by increasing levels of BASDAI, being zero at the highest quintile of BASDAI. GEE showed that both BASDAI and mSASSS independently and significantly helped to explain either BASFI or DFI. Results were similar for syndesmophyte sum score, non-syndesmophyte sum score, number of affected VUs or number of VUs with bridging. The lumbar part of the mSASSS contributed similarly to the cervical part in explaining BASFI/DFI. Conclusion: Physical function impairment in AS is independently caused by patient-reported disease activity and the level of structural damage of the lumbar and cervical spine. Syndesmophytes and other radiographic abnormalities contribute to physical function impairment.

Spinal radiographic changes in ankylosing spondylitis: association with clinical characteristics and functional outcome.

Abstract: Objective. To determine which patients with ankylosing spondylitis (AS) have radiographic spinal damage and to investigate the relation between radiographic spinal changes and limitations in physical function. Methods. A cross-sectional nationwide study in Belgium of patients with AS under the care of a rheumatologist. The treating physician completed a questionnaire including clinical disease manifestations and laboratory findings (HLA-B27 and C-reactive protein), and classified spinal radiographs into 3 categories: (1) no AS-related spinal abnormalities; (2) syndesmophytes; and (3) spinal ankylosis. Patients completed the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). Ordinal regressions were performed to quantify the relationship between clinical manifestations and spinal radiographic changes. Generalized linear models were computed to quantify relationships among clinical manifestations, radiographic spinal changes, and functioning (BASFI). Results. A total of 619 patients fulfilled modified New York criteria for definite AS and had evaluable radiographic data; 68% were male and disease duration was 17.5 (SD 12.2) years. Male sex, younger age at symptom onset, and hip involvement were associated with radiographic changes; but HLA-B27, peripheral arthritis, and extraarticular disease status (uveitis, psoriasis, and inflammatory bowel disease) were not. Older age, BASDAI, hip involvement, and spinal change contributed to BASFI; but sex, disease duration, peripheral arthritis, and extraarticular manifestations did not. Conclusion. Radiographic spinal changes in patients with AS are seen more often in men and those with hip involvement. BASFI status indicates the influence of radiographic changes and hip involvement, but does not reflect the presence of peripheral arthritis and does not differ between men and women.

Extra-articular manifestations.

Abstract: Rheumatoid arthritis and spondyloarthritis, a concept which includes diseases like ankylosing spondylitis, psoriatic arthritis, and arthritis/spondylitis associated with inflammatory bowel disease, are both chronic inflammatory rheumatologic conditions. This article focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. The different manifestations are addressed per body system. Diagnostic and prognostic implications of these manifestations in daily practice are discussed.

ASAS/EULAR recommendations for the management of ankylosing spondylitis: the patient version

Abstract: Background: The ASAS/EULAR (Assessment of SpondyloArthritis International Society/European League Against Rheumatism) recommendations for the management of ankylosing spondylitis (AS) have been developed by rheumatologists for a target population of health professionals. Objective: To extend the cooperation between ASAS and EULAR by translating the recommendations into a language that can be easily understood by patients in order to further disseminate and evaluate the recommendations. Methods: In cooperation with patient organisations 18 patients with AS (17 European, one Canadian) were invited to attend a meeting in February 2008. As a starting point the original publication and a version created by Canadian patients with AS were used. To improve the understanding of potential problems, data on the evaluation of a recent German translation were presented. After intensive discussions the wording was adjusted and a vote was held on the new wording of the recommendations aiming for >80% agreement on each sentence. Finally, patients were asked to indicate their level of agreement with the content of the recommendations. Results: Ten recommendations were successfully translated into a patient-understandable version. The original text was changed in most cases. In all but one case (recommendation No 4) there was broad agreement with the proposed translation. The overall agreement with the content of the recommendations was high: 8.7 (0.6). Conclusion: For the first time, EULAR recommendations were successfully converted into a patient-understandable language version by a large international group of patients in collaboration with rheumatologists. The evaluation showed broad agreement. Translations into different languages and further dissemination in individual countries will be performed.

Sensitivity and specificity of criteria for spondyloarthritis in children with late onset pauciarticular juvenile chronic arthritis as well as their characteristics

Abstract: Objective To evaluate the sensitivity and specificity of criteria designed for spondyloarthritis a university hospital treated Population of children with late onset pauciarticular juvenile, chronic arthritis and a control population. Methods Four sets of criteria especially designed for juvenile patients: Garmisch-Partenkirchen juvenile spondylitis criteria (= Garmisch), SEA (=seronegative enthesopathy and arthritis)syndrome, Enthesitis Related Arthritis (ERA), Atypical spondyloarthritis for children and two sets of criteria for patients without age specification (European spondyloarthropathy Study, Group - ESSG and Amor) were evaluated it? a cross-sectional way in a group of 43 consecutive patients with late onset pauciarticular juvenile chronic arthritis (LOPA) seen over a six-month period in the outpatient clinic. These criteria were analysed in 69 patients with other forms of juvenile chronic arthritis as well. The sensitivity and specificity were calculated for each set, as well as positive predictive value and likelihood ratio. The characteristics described in the different sets of criteria were separately evaluated in the LOPA patients and the other patients. Results For sensitivity, the Garmisch criteria scored the highest value (97.7%). However, sensitivity was significantly lower in two of the juvenile sets (SEA syndrome and Atypical spondyloarthritis), respectively 44.2% criteria (>85%; P 10 in SEA (30.5), ERA (18.7) and Garmisch (16.8). The negative likelihood ratio (LR-) was <0.1 only in the Garmisch criteria (0.02). Conclusion Sensitivity, specificity, PPV LR+ and LR- for the Garmisch-Partenkirchen criteria suggest that the), classify almost the same population (is defined by LOPA. The SEA syndrome criteria, which were not designed to be classification criteria, being very specific, cannot be used in this patient population to classify a sufficient number of patients. The sensitivity and specificity for the ESSG criteria being similar in these children as in adults suggest they have similar characteristics. The Garmisch-Partenkirchen criteria and/or LOPA definition are major candidates for future research it? identifying spondyloarthritis in juvenile patients.

Classification models for disease: the effect of associations between markers on calculating the risk for disease by likelihood ratio products.

Abstract: The risk, for disease or a bad prognosis cart be calculated by means of prediction or classification models that take into account multiple variables. Different methods exist to construct such models. Some of those methods, including the likelihood ratio (LR) product method neglect dependency between variables. We aimed to evaluate the effect of neglecting dependency between variables ill prediction or classification models. Patients and methods Population I consisted of 1003 consecutive patients with a new diagnostic problem for which RA was included ill the differential diagnosis and final diagnoses (RA or non-RA) were established after I Year. The baseline variables included in the model are rheumatoid factor, anti-citrullinated protein/peptide antibodies and the HLA-shared epitope. Population II consisted of 847 patients with definite ankylosing spondylitis (AS). Six variables (psoriasis, inflammatory bowel disease, uveitis, HLA-B27 status and latest available CRP) were evaluated. Here, specificities of the features were derived from literature and different scenarios of association between variables in controls and diseased are estimated. Results When two features are similarly associated in cases and controls, risks for disease will be overestimated by: neglecting dependency bell-veer variables. In the presented datasets, this resulted in a tip to 12% overestimation of the risk. Conclusions We showed how the height of over- or underestimation of risks can be evaluated when dependencies between two variables are neglected. This is important to evaluate the predictive value of combinations of features in cases where no data are available on associations ill controls.

Clinical observations programme in SpA: disease parameters, treatment options and practical management issues

Abstract: Spondyloarthritides (SpAs) are a cluster of chronic inflammatory rheumatic diseases that typically involve inflammation of axial and peripheral joint or tendon and ligament insertions, distinct radiographic changes and diverse extra-articular features. Conventional treatments relieve the signs and symptoms but do not prevent disease progression. TNFα inhibitors provide clinicians with the potential to treat the underlying pathology and to alter disease progression. By targeting the underlying inflammatory mechanisms, TNFα blockade can treat any extra-articular manifestations of SpA.

SpondyloArthritis international Society (ASAS) exercise by experts from the Assessment of patients with chronic back pain: a real patient New criteria for inflammatory back pain in

Abstract: Objective: Inflammatory back pain (IBP) is an importantclinical symptom in patients with axial spondyloarthritis(SpA), and relevant for classification and diagnosis. In thepresent report, a new approach for the development ofIBP classification criteria is discussed.Methods: Rheumatologists (n=13) who are experts inSpA took part in a 2-day international workshop toinvestigate 20 patients with back pain and possible SpA.Each expert documented the presence/absence of clinicalparameters typical for IBP, and judged whether IBP wasconsidered present or absent based on the receivedinformation. This expert judgement was used as thedependent variable in a logistic regression analysis inorder to identify those individual IBP parameters thatcontributed best to a diagnosis of IBP. The new set of IBPcriteria was validated in a separate cohort of patients(n=648).Results: Five parameters best explained IBP according tothe experts. These were: (1) improvement with exercise(odds ratio (OR) 23.1); (2) pain at night (OR 20.4); (3)insidious onset (OR 12.7); (4) age at onset ,40 years(OR 9.9); and (5) no improvement with rest (OR 7.7). If atleast four out of these five parameters were fulfilled, thecriteria had a sensitivity of 77.0% and specificity of 91.7%in the patients participating in the workshop, and 79.6%and 72.4%, respectively, in the validation cohort.Conclusion: This new approach with real patientsdefines a set of IBP definition criteria using overall expertjudgement on IBP as the gold standard. The IBP experts’criteria are robust, easy to apply and have good facevalidity.Chronic back pain is the leading symptom inpatients with axial spondyloarthritis (SpA) includ-ing patients with ankylosing spondylitis (AS).