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ABSTRACT: BACKGROUND: Anticitrullinated peptide antibodies (ACPA) and acute phase reactants may be increased before arthritis becomes clinically detectable, suggesting that the processes underlying rheumatoid arthritis (RA) start preclinically. Whether local inflammation occurs in the preclinical phase is unknown. Therefore, we studied the small joints of ACPA positive arthralgia patients for local subclinical inflammation. METHODS: Imaging was performed using 1.5 T extremity MRI. Painful hand or foot joints of 21 ACPA positive arthralgia patients without clinical arthritis were imaged. For comparison, hand and foot joints of 22 ACPA positive RA patients and 19 symptom free controls were studied. Within ACPA positive arthralgia patients, painful and symptom free joint regions were imaged. Scoring was performed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) method. Analyses were performed on joint region level and focused on inflammation (synovitis plus bone marrow oedema). RESULTS: The mean combined inflammation scores of the metacarpophalangeal/proximal interphalangeal joints of controls, painful joints of ACPA positive arthralgia patients and ACPA positive RA patients were 0.1, 0.7 and 3.7, respectively (p<0.001). Likewise, the mean combined inflammation scores of the wrist were 0.9, 2.3 and 10.3, respectively (p<0.001) and that of the metatarsophalangeal joints 0.5, 0.9 and 3.8, respectively (p=0.10). At the MCP joints, the combined inflammation score was significantly correlated with C reactive protein and erythrocyte sedimentation rate levels (r(s)=0.83 and r(s)=0.78, respectively) CONCLUSIONS: The present data suggest that local subclinical inflammation occurs in ACPA positive arthralgia patients.
Annals of the rheumatic diseases 01/2013; · 8.11 Impact Factor
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ABSTRACT: To give an overview of the recommendations for the use of anti-TNF-α therapy in AS in 23 countries worldwide.
The recommendations were collected, translated and a summary was checked by Assessment of SpondyloArthritis International Society (ASAS) members from the respective countries. The recommendations were compared with the ASAS recommendations (2006) on three aspects: patient selection for initiation of treatment (diagnosis, disease activity, previous treatment and contraindications), assessment of disease and assessment of response.
The majority of the recommendations are similar to the ASAS recommendation with regard to patient selection, assessment of disease and treatment response. Additional objective assessments of disease activity are required in eight countries, leading to a more strict indication to start anti-TNF-α therapy. CONCLUSION; Most national recommendations follow the international ASAS recommendations, suggesting that the latter are widely implemented. This might contribute to comparable access with anti-TNF-α treatment across countries. This article shows that general consensus exists about the use of anti-TNF-α therapy in AS across the world, although some countries require additional objective signs of inflammation and/or more pre-treatment, which limits access.
Rheumatology (Oxford, England) 12/2011; 50(12):2270-7. · 4.24 Impact Factor
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ABSTRACT: The Assessment of SpondyloArthritis International Society (ASAS) group has recently developed criteria to classify patients with axial SpA with or without radiographic sacroiliitis, and criteria to classify patients with peripheral SpA. The ASAS axial criteria consist of 2 arms and can be applied in patients with back pain (>3 months almost every day). In one arm, imaging (radiographs and magnetic resonance imaging [MRI]) has an important role, in the other arm--HLA-B27. MRI can detect active inflammation and structural damage associated with SpA. According to the ASAS axial SpA criteria, patients with chronic back pain aged less than 45 years at onset can be classified as having axial SpA if sacroiliitis on imaging (radiographs or MRI) plus 1 further SpA feature are present, or if HLA-B27 plus 2 further SpA features are present. The ASAS peripheral criteria can be applied in patients with peripheral arthritis (usually asymmetric arthritis predominantly involving the lower limbs), enthesitis, or dactylitis. Patients can be classified as having peripheral SpA if 1 of the following features is present: uveitis, HLA-B27, preceding genitourinary or gastrointestinal infection, psoriasis, inflammatory bowel disease, sacroiliitis on imaging (radiographs or MRI), or if 2 of the following features besides the entry feature are present: arthritis, enthesitis, dactylitis, inflammatory back pain, or a positive family history of SpA.
Polskie archiwum medycyny wewnȩtrznej 11/2010; 120(11):452-7. · 1.37 Impact Factor
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Diane van der Woude,
Silje W Syversen,
Ellen I H van der Voort,
Kirsten N Verpoort,
Guro L Goll,
Michael P M van der Linden,
Annette H M van der Helm-van Mil, Désirée M F M van der Heijde,
Tom W J Huizinga,
Tore K Kvien,
René E M Toes
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ABSTRACT: The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated.
To investigate the relationship between ACPA isotypes, disease progression and radiological outcome.
ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts.
The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors.
The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.
Annals of the rheumatic diseases 06/2010; 69(6):1110-6. · 8.11 Impact Factor
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Josef S Smolen, Désirée M F M Van Der Heijde,
E William St Clair,
Paul Emery,
Joan M Bathon,
Edward Keystone,
Ravinder N Maini,
Joachim R Kalden,
Michael Schiff,
Daniel Baker,
Chenglong Han,
John Han,
Mohan Bala
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ABSTRACT: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX.
Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54.
C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab.
High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.
Arthritis & Rheumatism 04/2006; 54(3):702-10. · 7.87 Impact Factor
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ABSTRACT: Depiction of inflammatory lesions by magnetic resonance imaging (MRI) in ankylosing spondylitis (AS) is possible both by short-tau inversion recovery (STIR) imaging and by gadolinium-enhanced T1-weighted imaging with fat saturation (T1/Gd). The aim of this prospective study was to investigate whether Gd-enhanced sequences add relevant information compared to STIR imaging alone in the detection of active spinal lesions. MRI of the spine was performed in 48 patients with AS, who participated in a clinical trial of tumor necrosis factor blocking drugs, by STIR and T1/Gd at baseline and after 6 months. Images were evaluated separately for the 2 techniques by 2 readers blinded for true time sequence and treatment. The ASspiMRI-a scoring method was used, in which 23 vertebral units are graded for inflammation from 0 to 6 (total score 0 to 138). Mean scorings of both techniques within readers were in the same range (reader 1: STIR 7.8, T1/Gd 7.7; reader 2: STIR 4.4, T1/Gd 4.7). Intraclass correlation coefficients comparing STIR and T1/Gd where high for both status scores (reader 1: 0.88; reader 2: 0.90) and change scores (both readers: 0.88). Bland and Altman analysis for both sequences showed homogeneous interreader variability along the entire spectrum of scorings, for both status scores and change scores. Smallest detectable change for status scores was 6.2 for STIR and 6.7 for T1/Gd, and for change scores 6.5 and 6.3, respectively. Standardized response means were comparable for both methods (range: 0.80-1.09). In conclusion, both STIR and T1/Gd sequences measure inflammation of the spine, as well as change of inflammation, with a high level of agreement between the 2 sequences. For future clinical randomized trials with MRI of the spine as outcome measure, STIR could be considered for use as the sole imaging technique.
The Journal of Rheumatology 11/2005; 32(10):2056-60. · 3.69 Impact Factor
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ABSTRACT: Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the spine is increasingly important in the assessment of inflammatory activity and structural damage in clinical trials with patients with ankylosing spondylitis (AS). We investigated inter-reader reliability and sensitivity to change of several scoring systems to assess disease activity and change in disease activity in patients with AS. Twenty sets of consecutive MRI, derived from a randomized clinical trial comparing an active drug with placebo and selected on the basis of the presence of activity at baseline, were presented electronically to 7 experienced readers from different countries (Europe, Canada). Readers scored the MRI by 3 different methods including: a global score (grading activity per SI joint); a more comprehensive global score (grading activity per SI joint per quadrant); and a detailed scoring system [Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system], which scores 6 images, divided into quadrants, with additional scores for "depth" and "intensity." A fourth and a fifth scoring system were constructed afterwards. The fourth method included the SPARCC score minus the additional scores for "depth" and "intensity," and the fifth method included the SPARCC slice with the maximum score. Inter-reader reliability was investigated by calculating intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs. Sensitivity to change was investigated by calculating standardized response means (SRM) on change scores that were made positive. Overall inter-reader ICC per method were between 0.47 and 0.58 for scoring status, and between 0.40 and 0.53 for scoring change. ICC per possible reader pairs showed much more fluctuation per method, with lowest observed values close to zero (no agreement) and highest observed values over 0.80 (excellent agreement). In general, agreement of status scores was somewhat better than agreement of change scores, and agreement of the comprehensive SPARCC scoring system was somewhat better than agreement of the more condensed systems. Sensitivity to change differed per reader, but in general was somewhat better for the comprehensive SPARCC system. This experiment under "real life," far from optimal conditions demonstrates the feasibility of scoring exercises for method comparison, provides evidence for the reliability and sensitivity to change of scoring systems to be used in assessing activity of SI joints in clinical trials, and sets the conditions for further validation research in this field.
The Journal of Rheumatology 11/2005; 32(10):2050-5. · 3.69 Impact Factor
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ABSTRACT: Magnetic resolution imaging (MRI) is a promising tool in the assessment of inflammation and structural damage in clinical trials in ankylosing spondylitis (AS). The ASAS/OMERACT MRI in AS working group, a collaborative initiative of rheumatologists and musculoskeletal radiologists with a special interest in this field, collected data on all available scoring methods for both sacroiliac (SI) joints and spine, and tested them with respect to the OMERACT filter. These data were presented together with the technical specifications of all methods at the OMERACT 7 conference. In addition, the results of 2 separate experiments on the inter-reader reliability of scoring methods to assess activity in SI joints, and on the comparison of STIR sequence versus T1 post-gadolinium (Gd) sequence for the spine, were presented. Thereafter, 8 groups discussed these data and proposed a research agenda, each on a different topic. This information was reported back to all participants and a prioritized research agenda was compiled by voting. Research on scoring methods for assessing disease activity, in both the spine and SI joints, was considered most important. Research on assessing structural damage was considered less important. The specific process and results of this initiative are discussed.
The Journal of Rheumatology 11/2005; 32(10):2042-7. · 3.69 Impact Factor
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ABSTRACT: To examine the baseline demographic and disease characteristics that might influence improvement as measured by the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) in patients with ankylosing spondylitis (AS).
A multicenter Phase 3 study was performed to compare the safety and efficacy of 24 weeks of etanercept 25 mg subcutaneous injection twice weekly (n = 138) and placebo (n = 139) in patients with AS. The ASAS 20 was measured at multiple time points. Using a significance level of 0.05, a repeated measures logistic regression model was used to determine which baseline factors influenced response in the etanercept-treated patients during the 24-week double blind portion of the trial. The following baseline factors were used in the model: demographic and disease severity variables, concomitant medications, extra-articular manifestations, and HLA-B27 status. The predictive capability of the model was then tested on the patients receiving placebo after they had received open-label etanercept treatment.
Baseline factors that were significant predictors of an ASAS 20 response in etanercept-treated patients were C-reactive protein (CRP), back pain score, and Bath Ankylosing Spondylitis Functional Index (BASFI) score. Although clinical response to etanercept was seen at all levels of baseline disease activity, responses were consistently more likely with higher CRP levels or back pain scores and less likely with increased BASFI scores at baseline.
Higher CRP values and back pain scores and lower BASFI scores at baseline were significant predictors of a higher ASAS 20 response in patients with AS receiving etanercept but predictive value was of insufficient magnitude to determine treatment in individual patients.
The Journal of Rheumatology 10/2005; 32(9):1751-4. · 3.69 Impact Factor
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E William St Clair, Désirée M F M van der Heijde,
Josef S Smolen,
Ravinder N Maini,
Joan M Bathon,
Paul Emery,
Edward Keystone,
Michael Schiff,
Joachim R Kalden,
Ben Wang,
Kimberly Dewoody,
Roberta Weiss,
Daniel Baker
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ABSTRACT: To compare the benefits of initiating treatment with methotrexate (MTX) and infliximab (anti-tumor necrosis factor alpha [anti-TNFalpha] monoclonal antibody) with those of MTX treatment alone in patients with rheumatoid arthritis (RA) of < or =3 years' duration.
RA patients were eligible if they had active disease and no prior treatment with MTX or a TNFalpha inhibitor. One thousand forty-nine patients were randomly assigned in a 4:5:5 ratio to 3 treatment groups: MTX-placebo, MTX-3 mg/kg infliximab, and MTX-6 mg/kg infliximab. MTX dosages were rapidly escalated to 20 mg/week, and infliximab or placebo infusions were given at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46.
At week 54, the median percentage of American College of Rheumatology improvement (ACR-N) was higher for the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than for the MTX-placebo group (38.9% and 46.7% versus 26.4%, respectively; P < 0.001 for both comparisons). Patients in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups also showed less radiographic progression than those receiving MTX alone (mean +/- SD changes in van der Heijde modification of the total Sharp score at week 54: 0.4 +/- 5.8 and 0.5 +/- 5.6 versus 3.7 +/- 9.6, respectively; P < 0.001 for each comparison). In addition, physical function improved significantly more in the MTX-3 mg/kg infliximab and MTX-6 mg/kg infliximab groups than in the MTX-placebo group. Infliximab therapy was associated with a significantly higher incidence of serious infections, especially pneumonia.
For patients with active RA in its early stages, combination therapy with MTX and infliximab provides greater clinical, radiographic, and functional benefits than treatment with MTX alone.
Arthritis & Rheumatism 11/2004; 50(11):3432-43. · 7.87 Impact Factor
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ABSTRACT: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression.
The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables.
Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients.
Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.
Arthritis & Rheumatism 08/2004; 50(7):2082-93. · 7.87 Impact Factor
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ABSTRACT: To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials.
The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points.
After 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, approximately 40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0.
The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials.
Arthritis & Rheumatism 08/2004; 50(8):2622-32. · 7.87 Impact Factor
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ABSTRACT: Objective
To select the most appropriate radiologic scoring method for the evaluation of radiographic progression in ankylosing spondylitis (AS) in clinical trials.Methods
The validity of the currently available methods, the Bath Ankylosing Spondylitis Radiology Index (BASRI), the Stoke Ankylosing Spondylitis Spine Score (SASSS), and the modified SASSS (M-SASSS), was tested according to the aspects of the Outcome Measures in Rheumatology Clinical Trials filter: truth, discrimination (reliability and sensitivity to change), and feasibility, using radiographs of 133 patients at 4 different time points (baseline, 1 year, 2 years, and 4 years). One observer scored these sets in chronological order. To assess interobserver reliability, a second observer scored radiographs of 20 patients at the 4 different time points.ResultsAfter 4 years, 9% and 8% of patients showed changes >0 in the sacroiliac (SI) joints and hips, respectively. Independent of the method chosen, ∼40% of patients showed changes in both the lumbar and cervical spine. Therefore, it was concluded that, for the assessment of progression, SI joints and hips are of minor importance. The intraclass correlation coefficient (ICC) varied from 0.87 to 0.98 and ICCs for intraobserver scores varied from 0.96 to 0.99. Concerning progression scores, only the ICC for the M-SASSS measured after 2 years remained acceptable (0.82). The intraobserver scores for progression after 2 years of followup were an ICC of 0.93 for the BASRI, an ICC of 0.79 for the SASSS, and an ICC of 0.95 for the M-SASSS. Concerning sensitivity to change, it was found that the M-SASSS classified the highest percentage of patients with a change >0.Conclusion
The M-SASSS is the most appropriate method by which to score the radiographic progression in AS patients in clinical trials.
Arthritis & Rheumatism 07/2004; 50(8):2622 - 2632. · 7.87 Impact Factor
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Désirée M F M van der Heijde
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ABSTRACT: Radiographs are important to assess structural damage in longitudinal studies. This article describes several issues on the selection of films, frequency of followup, scoring of radiographs, and presentation of results, especially in the context of longitudinal studies.
Journal of Rheumatology Supplement 04/2004; 69:46-7.
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ABSTRACT: To investigate the responsiveness and discriminative capacity, and the relationship between both, of instruments selected for the disease-controlling antirheumatic therapy (DC-ART) core set by the Assessments in Ankylosing Spondylitis Working Group (ASAS).
Responsiveness and discriminative capacity of different measures reflecting disease activity and function, either included in the ASAS DC-ART core set or not, were evaluated in a randomized controlled clinical trial comparing etanercept with placebo in patients with ankylosing spondylitis. Guyatt's method was used as the primary analysis for responsiveness, and Student's t-test for discriminative capacity.
At day 28 of therapy, almost all measures indicated moderate to large responsiveness in the etanercept group (Guyatt 0.60-3.11). Some scales of the Short Form 36 (general health, mental component summary, and role emotional), the modified Schober's test, and the Fatigue Severity Scale were not responsive. The results were similar if analyzed at day 112 of therapy. Peripheral joint counts, joint scores, and occiput-to-wall distance could not be evaluated due to a floor effect. In general, the relation between responsiveness and discriminative capacity was strong: Measures that demonstrated high responsiveness also showed high between-group t values.
Measures included in the ASAS DC-ART core set, except modified Schober's test, have good responsiveness and good discriminatory capacity. Some measures could not be evaluated due to a floor effect.
Arthritis & Rheumatism 03/2004; 51(1):1-8. · 7.87 Impact Factor
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ABSTRACT: Therapeutic possibilities for the treatment of early rheumatoid arthritis (RA) have expanded largely. New treatment modalities appear very effective with respect to relevant outcomes, such as radiographic progression. At the same time, the costs of disease-modifying antirheumatic drugs (DMARDs) have exponentially increased so that--given the rather high prevalence of RA--cost may become a limiting factor in the treatment of patients with RA. Therefore, there is a need to define the profile of those patients that should be treated with the most effective, and, unfortunately, the most costly, DMARDs. The authors describe herewith the heterogeneity of RA with respect to its most important outcomes, as well as the inability to predict those outcomes appropriately at the individual patient level. This heterogeneity of RA is not acknowledged in the modern landmark clinical trials that the authors base therapeutic decisions on, and the external validity of those trials is at stake. In this article, the authors discuss the consequences of the heterogeneity of RA in light of the perceived lack of external validity of evidence-generating landmark trials. The authors propose the following solutions to overcome this discrepancy: 1) earlier recognition of RA, and 2) appropriate prediction of treatment efficacy, because the most challenging scientific efforts may be taken in the near future in order to arrive at a tailor-made therapy for every individual presenting with RA.
Current Rheumatology Reports 09/2003; 5(4):287-93.
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ABSTRACT: Physicians apply assessments every day in clinical practice. Common clinical practice is impossible without measurements and tests. Testing looks rather straightforward: a test result is either positive or negative. Unfortunately, this simplicity is not in keeping with truth. At the base of measuring and testing in clinical practice lies the assumption of uncertainty: we do not know whether a patient has a disease, we can only estimate the probability that he has a disease by performing a (chain of) test(s). Every test result leaves open the chance that a wrong decision is taken on the basis of the test result. It is a challenge for the clinician to get a better insight into this process, as well as to minimize the chance of wrong decisions. By using a number of clinical examples, we describe here the principles of assessment from two different perspectives: the perspective of the test, and the perspective of the individual patient. The former perspective incorporates test-specific characteristics, such as sensitivity, specificity, accuracy and cut-off levels, and the latter deals with individual probabilities from a 'Bayesian' concept.
Bailliè re s Best Practice and Research in Clinical Rheumatology 07/2003; 17(3):365-79. · 2.65 Impact Factor
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Robert B M Landewé,
Maarten Boers,
Arco C Verhoeven,
Rene Westhovens,
Mart A F J van de Laar,
Harry M Markusse,
J Christiaan van Denderen,
Marie Louise Westedt,
Andre J Peeters,
Ben A C Dijkmans,
Piet Jacobs,
Annelies Boonen, Désirée M F M van der Heijde,
Sjef van der Linden
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ABSTRACT: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome.
All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline).
At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28.
An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.
Arthritis & Rheumatism 03/2002; 46(2):347-56. · 7.87 Impact Factor
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ABSTRACT: This article discusses methodological concepts and challenges underlying the interpretation of changes in plain radiographs of the joints of patients with rheumatoid arthritis. A series of consensus conferences (OMERACT [Outcome Measures in Rheumatology]) has resulted in the formulation and execution of a research agenda to harmonise reading and interpretation of films. This is important in the light of the increasing evidence that drugs can impact on the progression of joint damage. In these conferences, methodological issues have been divided according to applicability tenets summarised in the OMERACT Filter of Truth, Discrimination, and Feasibility. To pass the Filter, a measure must measure what it is supposed to measure (Truth), must discriminate between clinically relevant states (Discrimination) and be feasible in terms of costs and interpretability. 'Truth' issues include the choice of joints, the view and other technical specifications of the radiograph, such as which abnormalities to score, the level of aggregation of the information, culminating in the choice of the scoring system. 'Discrimination' issues include reproducibility and sensitivity to change. The current research agenda includes items such as defining a criterion for 'no relevant progression', comparison between time ordered and randomly ordered reading, further comparison of methods and subscores, and methodology around missing values.
Drugs 02/2002; 62(12):1717-24. · 4.23 Impact Factor
