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ABSTRACT: The ASAS/OMERACT MRI group recently described and defined magnetic resonance imaging (MRI) findings in sacroiliac joints (SIJ) that are essential for the diagnosis of sacroiliitis in patients with axial spondyloarthritis, including ankylosing spondylitis (AS). At the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 2010 meeting, a special interest group (SIG) was formed to design a research agenda for the definition and description of structural lesions in the SIJ and the spine in patients with established AS. During the SIG, a summary of the previous work of the group was presented to all participants, containing: (1) a description of the current definitions of structural SIJ changes; (2) available scoring methods for SIJ changes; (3) data from a previous pilot MRI exercise on chronic SIJ changes performed by members of the group; and (4) a proposal for a research agenda for OMERACT 11. The group agreed on the project's scientific merits and the need to evaluate all available scoring methods and to have clear definitions for all possible abnormalities that can be seen on MRI, prior to the start of the exercise. It was also agreed that the exercise should include scoring of both structural and inflammatory lesions, due to lack of agreement about the best scoring method for assessing both types of lesions in AS. Participants agreed that longitudinal MRI over a certain period are needed to learn about the time sequence of pathologic changes and to understand the course of the disease. Finally, participants asked the group to add the development of a scoring method for structural changes in the spine in a subsequent exercise. Further to these objectives, all experts who agreed to contribute in the exercise will collaborate to achieve consensus on definitions and to organize training in the different scoring systems prior to the start of the project, with the aim to finalize the multiple reader exercise by the end of 2011, in time for OMERACT 11.
The Journal of Rheumatology 09/2011; 38(9):2051-4. · 3.69 Impact Factor
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ABSTRACT: Hepatocyte growth factor (HGF) and dickkopf-1 (Dkk-1) inhibit osteoblast differentiation. The present study was thus undertaken to investigate whether plasma levels of HGF and Dkk-1 are related to bone damage in patients with rheumatoid arthritis (RA).
RA patients with a disease duration of <4 years were followed up prospectively with collection of demographic, clinical, and radiographic data at study enrollment (1992) and after 1, 2, 5, and 10 years. Hand radiographs were scored according to the modified Sharp/van der Heijde score (SHS). Levels of HGF and Dkk-1 in stored plasma samples obtained from 136 patients at the time of enrollment were measured by enzyme-linked immunosorbent assay. Associations between cytokine levels and radiographic progression were examined by linear regression analysis.
Patients with above-median levels of HGF at enrollment had a significantly greater change in the SHS after 1, 2, 5, and 10 years than did patients with below-median levels of HGF (P < 0.001, P = 0.006, P = 0.01, and P = 0.01, respectively). In an unadjusted analysis, baseline HGF levels predicted the severity of joint damage at all time points studied. After adjustment for other known predictors of radiographic progression, baseline HGF levels remained significantly associated with radiographic progression. Plasma levels of Dkk-1 at enrollment were not significantly associated with radiographic progression at any time point studied.
Plasma levels of HGF predict joint damage in RA, and this finding suggests that HGF plays a role in RA joint destruction. The role of HGF as a potential prognostic biomarker or target for treatment warrants further exploration.
Arthritis & Rheumatism 03/2011; 63(3):662-9. · 7.87 Impact Factor
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David T Felson,
Josef S Smolen,
George Wells,
Bin Zhang,
Lilian H D van Tuyl,
Julia Funovits,
Daniel Aletaha,
Cornelia F Allaart,
Joan Bathon,
Stefano Bombardieri, [......],
Tuulikki Sokka,
Vibeke Strand,
Peter Tugwell,
Alan Tyndall, Desirée van der Heijde,
Suzan Verstappen,
Barbara White,
Frederick Wolfe,
Angela Zink,
Maarten Boers
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ABSTRACT: Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition.
A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes.
Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (e.g., tender and swollen joint counts, C-reactive protein [CRP] level, and global assessments on a 0-10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year followup data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score-based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (a) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0-10 scale) are all ≤ 1, or (b) when the score on the Simplified Disease Activity Index is ≤ 3.3.
We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.
Arthritis & Rheumatism 03/2011; 63(3):573-86. · 7.87 Impact Factor
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Monika Schoels,
Rachel Knevel,
Daniel Aletaha,
Johannes W J Bijlsma,
Ferdinand C Breedveld,
Dimitrios T Boumpas,
Gerd Burmester,
Bernard Combe,
Maurizio Cutolo,
Maxime Dougados,
Paul Emery, Desirée van der Heijde,
Tom W J Huizinga,
Joachim Kalden,
Edward C Keystone,
Tore K Kvien,
Emilio Martin-Mola,
Carlomaurizio Montecucco,
Maarten de Wit,
Josef S Smolen
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ABSTRACT: To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment.
We conducted a systematic literature search including all clinical trials testing clinical, functional, or structural values of a targeted treatment approach. Our search covered Medline, Embase and Cochrane databases until December 2008 and also conference abstracts (2007, 2008).
The primary search yielded 5881 citations; after the selection process, 76 papers underwent detailed review. Of these, only seven strategic clinical trials were extracted: four studies randomised patients to routine or targeted treatment, two compared two different randomised targets and one compared targeted treatment to a historical control group. Five trials dealt with early RA patients. All identified studies showed significantly better clinical outcomes of targeted approaches than routine approaches. Disability was reported in two studies with no difference between groups. Four studies compared radiographic outcomes, two showing significant benefit of the targeted approach.
Only few studies employed randomised controlled settings to test the value of treatment to a specific target. However, they provided unanimous evidence for benefits of targeted approaches. Nevertheless, more data on radiographic and functional outcomes and on patients with established RA are needed.
Annals of the rheumatic diseases 04/2010; 69(4):638-43. · 8.11 Impact Factor
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Josef S Smolen,
Daniel Aletaha,
Johannes W J Bijlsma,
Ferdinand C Breedveld,
Dimitrios Boumpas,
Gerd Burmester,
Bernard Combe,
Maurizio Cutolo,
Maarten de Wit,
Maxime Dougados, [......],
Boulos Haraoui,
Joachim Kalden,
Edward C Keystone,
Tore K Kvien,
Iain McInnes,
Emilio Martin-Mola,
Carlomaurizio Montecucco,
Monika Schoels,
Désirée van der Heijde, Desirée van der Heijde
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ABSTRACT: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA).
/st> To develop recommendations for achieving optimal therapeutic outcomes in RA.
A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived.
The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (> or =9/10).
The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.
Annals of the rheumatic diseases 03/2010; 69(4):631-7. · 8.11 Impact Factor
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ABSTRACT: Ankylosing spondylitis (AS) is associated with bone loss in the vertebrae and an increased prevalence of vertebral fractures, but literature about the magnitude of the risk of fracturing is limited. One retrospective cohort study provided evidence of an increased risk of clinical vertebral fractures but not of non-vertebral fractures. This study further explores the risk of clinical vertebral and non-vertebral fractures in a large population database.
In a primary care-based nested case-control study, 231,778 patients with fracture and 231,778 age- and sex-matched controls were recruited. A history of AS was assessed from the medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated after adjustment for medication, other illnesses, smoking and body mass index when known.
AS was diagnosed in 758 subjects. The prevalence of AS was 0.18% in patients with fracture and 0.15% in controls. Patients with AS had an increased risk of clinical vertebral fracture (OR 3.26; 95% CI 1.51 to 7.02). The risk of fractures of the forearm and hip was not significantly increased (OR 1.21; 95% CI 0.87 to 1.69 and OR 0.77; 95% CI 0.43 to 1.37, respectively). The risk of any clinical fracture was increased in patients with AS with a history of inflammatory bowel disease (OR 2.79; 95% CI 1.10 to 7.08), whereas it was decreased in patients with AS taking non-steroidal anti-inflammatory drugs (OR 0.65; 95% CI 0.50 to 0.84). The risk was not associated with recent back pain, psoriasis, joint replacement therapy and use of sulfasalazine.
Patients with AS have an increased risk of clinical vertebral fracture but not of non-vertebral fractures, while the risk of any clinical fracture is increased in patients with concomitant inflammatory bowel disease. The mechanism by which non-steroidal anti-inflammatory drugs reduce the risk of any clinical fracture warrants further research.
Annals of the rheumatic diseases 01/2009; 68(12):1839-42. · 8.11 Impact Factor
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Dafna D Gladman,
Robert D Inman,
Richard J Cook,
Walter P Maksymowych,
Jurgen Braun,
John C Davis,
Robert B M Landewé,
Philip Mease,
Joachim Brandt,
Ruben Burgos Vargas, [......],
Arthur Kavanaugh,
Finbar D O'Shea,
Muhammad A Khan,
Nicolo Pipitone,
Proton Rahman,
John D Reveille,
Millicent A Stone,
William Taylor,
Douglas J Veale, Desirée van der Heijde
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ABSTRACT: To determine whether the assessments of peripheral joints and enthesitis were reproducible for both AS and PsA with axial disease, and whether dactylitis assessment is reproducible in patients with PsA.
A group of 20 rheumatologists from 11 countries with expertise in spondyloarthritis (SpA) met for a combined physical examination exercise to assess 10 patients with PsA with axial involvement (9 men, 1 woman, mean age 52 yrs, disease duration 17 yrs) and 9 patients with AS (7 men, 2 women, mean age 38 yrs, disease duration 16 yrs). A modified Latin-square design that enabled assessment of patient, assessor, and order effect was used. Measures included were number of tender and swollen joints, presence of enthesitis using 6 different indices, and dactylitis score. Data were analyzed using intraclass correlation (ICC) adjusted for order of measurements.
The majority of the variance was contributed by the patients. There was no order effect. The assessment of tender joints (ICC 0.69) was more reliable than the assessment of swollen joints (ICC 0.54). Moreover, there was better agreement in patients with PsA (ICC 0.78) than in patients with AS (ICC 0.62). There was excellent agreement on the number of active enthesitis sites (ICC 0.86). All the enthesitis indices provided substantial to excellent agreement among observers. Agreement for the dactylitis score was substantial (ICC 0.70).
The assessment of peripheral joints is more reliable in patients with PsA. Enthesitis instruments can be used reliably in patients with AS and patients with PsA with spinal involvement. The Leeds dactylitis instrument functions well in PsA.
The Journal of Rheumatology 09/2007; 34(8):1740-5. · 3.69 Impact Factor
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Dafna D Gladman,
Robert D Inman,
Richard J Cook, Desirée van der Heijde,
Robert B M Landewé,
Jurgen Braun,
John C Davis,
Philip Mease,
Joachim Brandt,
Ruben Burgos Vargas, [......],
Arthur Kavanaugh,
Finbar D O'Shea,
Muhammad A Khan,
Nicolo Pipitone,
Proton Rahman,
John D Reveille,
Millicent A Stone,
William Taylor,
Douglas J Veale,
Walter P Maksymowych
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ABSTRACT: To determine whether the axial measures used in primary ankylosing spondylitis (AS) were reproducible for both AS and psoriatic arthritis (PsA) with axial disease.
A group of 20 rheumatologists from 11 countries with expertise in spondyloarthritis (SpA) met for a combined physical examination exercise to assess 10 patients with PsA with axial involvement (9 men, 1 woman, mean age 52 yrs, mean disease duration 17 yrs) and 9 AS patients (7 men, 2 women, mean age 38 yrs, mean disease duration 16 yrs). A modified Latin-square design was used. Measures included were occiput to wall, tragus to wall, cervical rotation, chest expansion, lateral spinal bending, modified Schober, and hip mobility. Data were analyzed using intraclass correlation coefficients (ICC) adjusted for order of measurements.
The majority of the variance was contributed by the patients. There was no order effect. Observer effect was noted especially for chest expansion for both AS and PsA patients, and for the modified Schober in PsA. The ICC demonstrated very good to excellent agreement for most measures for both AS and PsA. Chest expansion provided only moderate agreement for AS and PsA.
Overall, measures of spinal mobility used in primary AS perform well with respect to interobserver reliability, and are equally reproducible when applied to PsA patients with axial involvement. Thus, these measures should now be evaluated in therapeutic trials of patients with PsA to determine sensitivity to change and concordance with other measures of structural damage.
The Journal of Rheumatology 09/2007; 34(8):1733-9. · 3.69 Impact Factor
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ABSTRACT: To evaluate the smallest detectable difference (SDD) of symptomatic outcome or process variables in ankylosing spondylitis (AS) patients from various countries.
Thirty consecutive AS patients with axial involvement were recruited from 1 center in each of 4 countries (Spain, Morocco, France, The Netherlands), for a total of 120 patients. Fourteen variables were studied in 6 domains: pain (3 variables), stiffness (1 variable), function (2 variables), spinal mobility (3 variables), patient global assessment (4 variables), and the domain of enthesiopathy (1 variable). All patients were evaluated twice within a 1-week period during which no clinical or therapeutic change occurred. Intracenter reliability was evaluated using the intraclass correlation coefficient (ICC). The SDD was determined using the Bland-Altman method.
Of the 14 variables evaluated in the 120 patients (82% males, 42 +/- 12 years old, with a mean disease duration of 17 +/- 13 years), only the SDD for the variable occiput-to-wall distance showed statistically significant difference among centers. For the entire group, the SDD, expressed as percentage of the range of the variable, varied from 10% (Mander enthesis index) to 39% (spinal pain at night last week). The intraobserver reliability was good (ICC > 0.80) except for the variables morning stiffness and modified Schober test (ICCs of 0.76 and 0.60, respectively).
This study suggests that the evaluation of AS patients is homogenous and reliable in different centers of different European and North African countries. Evaluation of the SDD of the symptomatic outcome or process variables is a starting point to determine the minimum clinically important difference, permitting the presentation of results of clinical studies on an individual basis.
Arthritis & Rheumatism 01/2003; 47(6):582-7. · 7.87 Impact Factor
