Rheumatoid Arthritis: Bruynesteyn K

Bruynesteyn K, Boers M, Kostense P, van der Linden S, van der Heijde D. · Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. · Ann Rheum Dis. · Pubmed #15286006 links to  free full text

Abstract: Progression of radiological joint damage is usually based on the simultaneous assessment of a series of films from an individual patient ("paired", with or without known sequence). In this setting the degree of progression that can be reliably detected above the measurement error is best determined by the smallest detectable change, and overestimated by the traditionally calculated smallest detectable difference. This knowledge is important for calculation of the proportion of patients showing radiographic progression in clinical trials.

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 Heijde D, Boers M, van der Linden S, Lassere M, van der Vleuten C. · Department of Internal Medicine, Division of Rheumatology, University of Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands. · J Clin Epidemiol. · Pubmed #15196621 No free full text.

Abstract: OBJECTIVE: To test the reliability of two radiologic scoring methods in rheumatoid arthritis (RA)--the Sharp/van der Heijde (SvH) and the Larsen/Scott (LS)--with generalizability analyses. STUDY DESIGN AND SETTING: Films of 51 patients representing the spectrum of early RA were read by two raters for each method. The discriminative ability and responsiveness were expressed as: intraclass correlation coefficients (ICCs), two types of smallest detectable difference (SDD), and two types of smallest detectable change (SDC); reflecting measurement error when discriminating between or detecting changes within (1) individuals or (2) groups. They were calculated for (average) scores of one to three raters. RESULTS: The discriminative capacity (0.85-0.97) and responsiveness (0.91-0.97) were good when expressed by ICC. On the group level the SDDs and SDCs ranged between 0.6-3.3% of the max. obtainable score. On the individual level, the scores showed better reliability measured with the SvH (SDDs 2.0-3.4%) than with the LS (SDDs 5.3-9.2%). The SvH also assessed changes in scores in individuals with less measurement error (SDCs 1.3-2.2%) than the LS (SDCs 2.3-3.9%). CONCLUSION: For early RA patients, the SvH seems preferable if analyses on individual level are included.

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.

Bruynesteyn K, Landewé R, van der Linden S, van der Heijde D. · Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. · Ann Rheum Dis. · Pubmed #15037445 links to  free full text

Abstract: OBJECTIVES: To investigate whether plain radiographs can show changes in joint damage due to rheumatoid arthritis (RA) within 3 months. METHODS: 188 film pairs taken with a 3 month interval were evaluated. They were scored with (chronological) and without (paired) knowledge of the sequence of the films according to the Sharp/van der Heijde method. Changes in joint damage were analysed on a group and an individual level for different subsets of patients. Sample sizes required to detect statistically and clinically significant differences were estimated based on the percentages of patients with progression larger than the smallest detectable change (SDC). RESULTS: Changes in joint damage were seen by both the chronological and the paired scoring method. The percentage of patients with progression of joint damage larger than the corresponding SDCs (1.7 and 2.4) varied in the subsets from 18% to 64% if based on the chronological change-scores and from 9% to 36% using paired change-scores. Acceptable sample size estimates were seen in several subsets, depending on (a) how the investigated drug would reduce the individual risk of progression of joint damage (by an absolute or a relative risk reduction model); (b) how damage was scored (chronological or paired); (c) the baseline risk; and (d) whether a two sided or one sided test would be used. CONCLUSIONS: Changes in joint damage due to RA can be detected reliably already within 3 months. This finding can be used to plan short term, randomised controlled trials with radiographic progression as primary outcome.

Sharp JT, Van Der Heijde D, Boers M, Boonen A, Bruynesteyn K, Emery P, Genant HK, Herborn G, Jurik A, Lassere M, McQueen F, Østergaard M, Peterfy C, Rau R, Strand V, Wassenberg S, Weissman B, Anonymous00464. · University of Washington, Seattle, Washington, USA. · J Rheumatol. · Pubmed #12734916 No free full text.

Abstract: The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.

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.

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. · Maastricht University, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #11953967 No free full text.

Abstract: OBJECTIVE: To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. METHODS: The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. RESULTS: The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). CONCLUSION: This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.

Lassere MN, van der Heijde D, Johnson K, Bruynesteyn K, Molenaar E, Boonen A, Verhoeven A, Emery P, Boers M. · Department of Rheumatology, St George Hospital, NSW, Sydney, Australia. · J Rheumatol. · Pubmed #11327275 No free full text.

Abstract: The smallest detectable difference (SDD) reflects that component of a measure statistically attributable to error from the measurement process itself. As such it is an irreducible component of the inherent variability in measurements in clinical trials and will affect their design, whether randomized or observational. Even though the application of the SDD concept to assaying radiographs in rheumatoid arthritis is relatively new and not well understood, systematic work on the influences of radiographic SDD can be done. This report describes the effects of a number of clinical aspects of the disease and operational aspects of trials on the values of the SDD of radiographic progression data. We show that if conditions affecting SDD are known and kept constant across datasets, the SDD of radiological progression from one study may be generalizable to other studies. However, if any one condition varies, the SDD is distinctly unrobust and cannot be generalized to other studies.

Bruynesteyn K, van der Heijde D, Boers M, Lassere M, Boonen A, Edmonds J, Houben H, Paulus H, Peloso P, Saudan A, van der Linden S. · Department of Rheumatology, University Hospital Maastricht, The Netherlands. · J Rheumatol. · Pubmed #11327274 No free full text.

Abstract: To determine the minimal clinically important difference (MCID) between hand and foot films with a 1 year interval assessed with the Sharp/van der Heijde or Larsen/Scott scoring method. Progression scores of the 2 methods were compared with the opinion of an international expert panel on clinical relevance of radiological joint damage in 4 predefined clinical settings. The expert panel consisted of 3 rheumatologists, who evaluated 46 pairs of hand and foot films, taken with 1 year intervals, of patients with early rheumatoid arthritis. Receiver operating characteristics curves analyzed the accuracy of different threshold values (progression scores) of the 2 scoring methods to detect the presence or absence of clinically important difference, as defined by the expert panel as external criterion. The threshold value with the highest accuracy was subsequently chosen as the score representing the MCID. Five Sharp/van der Heijde units and 2 Larsen/Scott units were the best cutoffs. The accompanying sensitivities ranged from 77% to 100% for the Sharp/van der Heijde method and from 73% to 84% for the Larsen/Scott method for the 4 clinical settings. The specificities were between 78% and 84% for the Sharp/van der Heijde method and between 74% and 94% for the Larsen/Scott method. The smallest progression score that can be detected apart from interobserver measurement error, the smallest detectable difference (SDD), was equal to or larger than the calculated MCID, 5 Sharp/van der Heijde units and 6 Larsen/Scott units in our study, if the mean progression scores of the same 2 observers were used. The SDD is a conservative estimate of the MCID; our panel rated progression at or below this level as clinically significant.