Rheumatoid Arthritis: Van Der Linden S

Korthals-de Bos I, Van Tulder M, Boers M, Verhoeven AC, Adèr HJ, Bibo J, Boonen A, Van Der Linden S. · Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #15338488 No free full text.

Abstract: OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

Garnero P, Landewé R, Boers M, Verhoeven A, Van Der Linden S, Christgau S, Van Der Heijde D, Boonen A, Geusens P. · INSERM Research Unit 403, and Synarc, Lyon, France. · Arthritis Rheum. · Pubmed #12428224 links to  free full text

Abstract: OBJECTIVE: The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. METHODS: This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). RESULTS: In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). CONCLUSION: High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation.

Bruynesteyn K, Van Der Heijde D, Boers M, Verhoeven A, Boonen A, Van Der Linden S, Anonymous00326. · University of Maastricht, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #12382303 links to  free full text

Abstract: OBJECTIVE: In rheumatoid arthritis (RA) in the context of a drug trial, prevention of erosions in undamaged joints is often considered more important than prevention of progression in already damaged joints, although a clear rationale is lacking. The aim of this study is to evaluate the relative contribution of separate components of the erosion score of the modified Sharp/van der Heijde method in early RA. METHODS: Different aspects of erosive damage were evaluated by their ability to discriminate between the 2 treatments in an early RA trial (the COBRA trial). RESULTS: The contribution of progression of already eroded joints to the total erosion score clearly increased during the 1.5 years of the trial. When the periods 0-28, 28-56, and 56-80 weeks were analyzed separately, the erosion score showed a significant difference between the groups in the first 2 periods (P < 0.0001, P < 0.03, and P < 0.64, respectively). Similar differences were seen in rates of progression in previously eroded joints (P = 0.005, P = 0.003, P = 0.35). On the other hand, rates of progression in newly eroded joints showed no significant difference between the 2 treatment groups in the second and third period (P < 0.0001, P < 0.16, P < 0.87). Analyses on joint and patient level showed analogous results. CONCLUSION: Subanalyses on progression rates in noneroded joints and already eroded joints can provide additional information. However, important information and discriminative strength may be lost when assessment is limited to the development of erosions in undamaged joints.

Bruynesteyn K, Van Der Linden S, Landewé R, Gubler F, Weijers R, Van Der Heijde D. · Department of Internal Medicine, Division of Rheumatology and the Department of Radiology, University Hospital Maastricht, Maastricht, The Netherlands. · J Rheumatol. · Pubmed #15170919 No free full text.

Abstract: OBJECTIVE: In a former study a panel of rheumatologists was used to assess which progression in radiological joint damage due to rheumatoid arthritis (RA) on hand and foot radiographs taken at one-year intervals was considered the minimally clinically important difference (MCID). We compare the judgments of the panel of rheumatologists with the judgments of 2 musculoskeletal radiologists. METHODS: Two experienced musculoskeletal radiologists evaluated independently the same hand and foot radiographs as assessed by the panel of rheumatologists. Progression was defined as important if the radiologist would state it as substantial progression in their report. Two readers, different from the radiologists and rheumatologists, independently obtained the Sharp/van der Heijde scores. Receiver operating characteristic curve analyses were performed to quantify the minimally important progression defined by the radiologists expressed in Sharp/van der Heijde change-scores. The change-score with the highest accuracy represented the minimally important progression and was compared with the MCID defined by the panel of rheumatologists for 4 different settings (early versus advanced RA and mild versus high disease activity). RESULTS: The minimally important progression defined by the radiologists was estimated at 6.5 Sharp/van der Heijde units. This was larger than the MCID defined by the panel of rheumatologists in 3 of the 4 clinical settings (3.0-4.5 units) and similar to the setting "advanced RA, mild disease activity." The panel of rheumatologists was inclined to change therapy in cases not reported as substantially progressive by the radiologists. The Sharp/van der Heijde progression scores of the radiographs on which the radiologists and rheumatologists disagreed related better with the rheumatologists' opinions. CONCLUSION: Changes that were not regarded as substantial by the radiologists were judged clinically important by the rheumatologists in 3 of the 4 clinical settings. Thus, the radiologists appeared to be reserved in judging changes as important.

Chorus AM, Miedema HS, Boonen A, Van Der Linden S. · Division of Public Health, TNO Prevention and Health, Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #14644855 links to  free full text

Abstract: OBJECTIVE: To investigate the relationship between work and quality of life (QOL) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) aged 16-59. METHODS: 1056 patients with RA and 658 with AS were included in the study. Data were obtained by postal questionnaire, which included several generic and disease related QOL instruments. Separate dimensions and physical and mental summary scores from the SF-36 were compared. Stepwise multiple regression was performed to study the relationship between work and physical and mental health related QOL, including disease related factors, coping, and fatigue. RESULTS: Physical health related QOL was reported to be worse, and mental health related QOL better, in RA than in AS in people of working age. No differences between RA and AS were found in somatic pain, physical role functioning, social functioning, emotional role functioning, vitality, or general health perception; nor were there any significant differences in fatigue and behavioural coping styles. Work was positively associated with physical health related QOL in both groups and, after disease characteristics, was the most important determinant. No association was found with mental health related QOL. CONCLUSIONS: Although physical health related QOL was worse in patients with RA, the impact on several dimensions of health related QOL in patients with RA and AS of working age under rheumatological care was comparable. Patients with RA and AS experienced similar limitations in physical role functioning, including work. Work is an important independent external determinant of physical health related QOL, but not of mental health related QOL.

Bruynesteyn K, Van Der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, Boonen A, Van Der Linden S. · Division of Rheumatology, Maastricht University, Maastricht, The Netherlands. · J Rheumatol. · Pubmed #12415585 No free full text.

Abstract: OBJECTIVE: To evaluate whether knowledge of the chronological sequence influences the sensitivity and specificity of the Sharp/van der Heijde (SvH) and Larsen/Scott (LS) scoring method to detect clinically important progression of joint damage caused by rheumatoid arthritis (RA) in the individual patient and assess whether scoring in chronological order leads to better sensitivity at the cost of lower specificity. METHODS: For both scoring methods, progression scores obtained with (chronological) and without knowledge of the sequence of the films (paired) were compared with the judgment of an international expert panel. This panel assessed whether progression of joint damage seen on films with 1 year intervals was clinically relevant (defined as progression of joint damage that would make clinicians change therapy). The applied thresholds for clinical relevance were (1) the progression scores with the highest accuracy by receiver operating characteristics analyses for the expert opinion, and (2) the smallest progression score that can be detected apart from interobserver measurement error by the scoring method, i.e., the smallest detectable difference (SDD). RESULTS: Progression scores that detected clinically relevant progression most accurately (chronological: 3.0 SvH units and 2.0 LS units; paired: 2.5 SvH units and 1.5 LS units) were smaller than the SDD (chronological 5.0 SvH units and 5.8 LS units; paired 13.8 SvH units and 9.7 LS units). With the SDD as threshold, the sensitivity to detect clinically relevant progression increased significantly from 20 to 60% for the SvH method and from 23 to 33% for the LS method if the sequence of the films was known. The specificity remained good when scoring chronologically: 88% for the SvH and 100% for the LS. CONCLUSION: Our results suggest that knowing the chronological sequence leads to an increase in detecting clinically relevant changes in the patient without serious overestimation of nonrelevant differences. Analyzing a clinical trial should be done preferably by reading films in chronological order.