Rheumatoid Arthritis: Paulus H

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Wong AL, Wong WK, Harker J, Sterz M, Bulpitt K, Park G, Ramos B, Clements P, Paulus H. · Department of Rheumatology, Olive View-UCLA Medical Center, Sylmar, California 91326, USA. · J Rheumatol. · Pubmed #10606362 No free full text.

Abstract: OBJECTIVE: To determine the correlation between patient self-report joint counts and standard physician joint counts, and to compare pictorial (Mannequin) and text (Rapid Assessment of Disease Activity in Rheumatology, RADAR) formats for obtaining patient self-reports. METHODS: Baseline patient self-report joint counts were mailed and completed by 60 patients with early rheumatoid arthritis (RA) one day before and one day after being examined by a physician. Twenty-seven were randomized to the Mannequin tender and Mannequin swollen joint counts; 33 were randomized to the RADAR tender and swollen joint counts. Agreement between patient and physician self-report joint counts, diagnostic characteristics, and test-retest reliability of patient self-report joint counts was computed. Stepwise regression analyses were performed to identify predictors of patient-physician differences in total joint count. RESULTS: Means and standard deviations of paired patient and physician total joint counts were not different for Mannequin or RADAR forms. Spearman correlations were moderate (0.58 to 0.69 for Mannequin, 0.37 to 0.58 for RADAR). Agreement (intraclass correlations) was 0.65 for the Mannequin and 0.56 for the RADAR forms. Patient test-retest reproducibility was moderate for RADAR tenderness (0.58) and high (r>0.90) for RADAR swollen and both Mannequin forms. Level of patient education predicted patient-physician differences on the RADAR swollen joint counts (p = 0.003), but was not significant in Mannequin forms, suggesting that education was not a factor in accurate completion of Mannequin forms. CONCLUSION: Both pictorial and text format patient self-report joint counts are significantly correlated with physician joint counts. In addition to moderately high patient test-retest reproducibility, this suggests that patient self-reports in both formats may yield accurate measures of improvement in disease activity.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Goldman JA, Xia HA, White B, Paulus H. · Division of Rheumatology, Emory University School of Medicine, Medical Quarters 5555 Peachtree-Dunwoody Road, Atlanta, GA 30342-1711, USA. · Ann Rheum Dis. · Pubmed #17105853 No free full text.

Abstract: OBJECTIVE: To evaluate a modified American College of Rheumatology 20 (mACR20) scoring system for patients with rheumatoid arthritis. METHODS: The data were evaluated from one study on patients with methotrexate (MTX)-naive early rheumatoid arthritis (ERA) and another study on patients with DMARD-refractory late rheumatoid arthritis (LRA). For mACR20 scoring, acute-phase reactant measurements were excluded, and 20% improvement from baseline was determined by 2 or 3 of the 4 remaining ACR components. RESULTS: For full joint counts with data from patients with ERA, marked differences favoured 25 mg etanercept (ETN) over 10 mg ETN by using the unmodified ACR20 (69% v 55%), the mACR20(3 of 4) (63% v 49%) and the mACR20(2 of 4) (72% v 58%). An assessment of 28 joints showed similar findings. In the trial on patients with LRA, considerably more patients in both ETN groups achieved a clinical response compared with placebo by using the ACR20, the mACR20(3 of 4) and the mACR20(2 of 4), whether using full or 28 joint counts. The mACR20(3 of 4) and full joint counts with data on patients with ERA showed a marked difference between the MTX and 10 mg ETN groups (63% v 49%), which was not observed with the ACR20. CONCLUSION: Patterns of improvement indicated by mACR20 scores were consistent with standard ACR20 scores.

Singh JA, Solomon DH, Dougados M, Felson D, Hawker G, Katz P, Paulus H, Wallace C, Anonymous00073. · No affiliation provided · Arthritis Rheum. · Pubmed #16739201 links to  free full text

Abstract: RELEVANCE TO THE CLINICIAN: Clinicians already know that not all patients who are diagnosed with rheumatic diseases really have them. Moreover, determining which patients have improved and by how much is also difficult. Classification criteria allow clinical researchers to recruit patients with similar diseases (e.g., rheumatoid arthritis or systemic lupus erythematosus) into studies. Response criteria help to determine whether treatments really work, i.e., whether they actually produce clinically important improvement. As the science of clinical research advances, we must update our standards for considering classification and response criteria. In this editorial, members of the American College of Rheumatology (ACR) Subcommittee on Classification and Response Criteria describe the purpose of criteria sets, their development and validation, and the role of the ACR in adopting them.

Sharp JT, Wolfe F, Lassere M, Boers M, Van Der Heijde D, Larsen A, Paulus H, Rau R, Strand V. · University of Washington School of Medicine, Seattle, Washington, USA. · J Rheumatol. · Pubmed #15170916 No free full text.

Abstract: OBJECTIVE: To determine the extent of precision and sources of variability among experts on scoring radiographic abnormalities in rheumatoid arthritis. METHODS: Radiographic scores from 6 datasets in which 2 or more readers had scored film sets were analyzed. Datasets included scores by 11 different readers, 6 of whom scored films by both the Larsen (global) and Sharp (composite) methods. Scores of each possible combination of 2 readers were compared in calculating the smallest detectable difference (SDD) on raw scores and on scores normalized for each individual reader (nSDD). Intraclass correlation (ICC), Pearson's r, and the correlation between differences in score and their mean scores were determined. Agreement on progression of radiographic damage scores was also examined. RESULTS: Variability among readers was greater than previous studies suggested. Agreement was better for intra- than interreader comparisons; average intrareader SDD was 24.4 for the composite method and 9.0 for the global. The larger SDD for the composite method reflect their greater range of possible scores. When normalized scores were used to adjust for the range difference, there was minimal difference in the SDD; nSDD was 10.1 for the composite method, 8.0 for the global. Interreader variability was larger: SDD of 53.7 for the composite method and 23.3 for the global; nSDD 12.9 and 14.4, respectively. ICC varied between 0.465 and 0.999, with all but one value below 0.925 occurring in composite scores with a range below 100. Differences in repeated scores were frequently associated with the mean of those scores and this was greater for inter- than for intrareader comparisons. Agreement between progression scores showed a similar pattern. The SDD was better for intrareader comparisons and smaller for global scores: compare 13.7 (composite, intrareader) and 5.4 (global, intrareader) to 18.1 (composite, interreader) and 8.7 (global, interreader). The ICC was lower for progression scores than for raw scores, averaging between 0.661 and 0.885. CONCLUSION: The variability in scoring radiographic abnormalities is considerable among this group of 11 expert readers. This has important implications for power calculations in comparison studies such as therapeutic trials and for cross-trial comparisons. The correlation between the difference in repeated scores and their means indicates systematic error (bias), which, if corrected, may improve the detection of treatment effects when using a responder-type analysis. These and other design and analysis issues are discussed.

Russak SM, Croft JD, Furst DE, Hohlbauch A, Liang MH, Moreland L, Ofman JJ, Paulus H, Simon LS, Weisman M, Tugwell P, Anonymous00333. · Zynx Health Incorporated, Beverly Hills, California, USA. · Arthritis Rheum. · Pubmed #12910566 links to  free full text

Abstract: OBJECTIVE: The utilization of health-related quality of life (HRQOL) patient questionnaires by clinical rheumatologists is limited. Yet, considerable literature exists defining the value of such data. In an effort to understand this apparent paradox, we performed a literature review and conducted a survey to describe what has been learned over the past 2 decades concerning the use of these measures in clinical care and explore the reasons for their underutilization. METHODS: A panel of rheumatologists with extensive clinical experience was convened to review the relevant literature pertaining to the use of HRQOL patient instruments in clinical practice. Additionally, a survey of all American College of Rheumatology practicing clinicians was conducted to assess the use of and beliefs about these measures. RESULTS: The literature provided evidence to support the use of HRQOL patient measures in clinical practice. Forty-seven percent of the responding rheumatologists stated that none of their patients complete HRQOL patient questionnaires. The majority of respondents (63%) reported that such information is "somewhat valuable." The most frequently reported reason for the underutilization was that such instruments "require too much staff time." CONCLUSIONS: The literature supports the potential value of HRQOL patient questionnaires in clinical practice. Few rheumatologists routinely gather such information as part of patient care. Reasons for this discrepancy between utility and use are given along with recommendations intended to help increase their utilization in clinical care.

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.

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.

Molenaar ET, Boers M, van der Heijde DM, Alarcón G, Bresnihan B, Cardiel M, Edmonds J, Felson D, Furst DE, Kirwan J, Lassere M, Paulus H, Rau R, van Riel PL, Scott D, Simon L, Strand V. · Department of Rheumatology, VU University Hospital, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #10090196 No free full text.

Abstract: None of the current scoring methods for radiological damage in rheumatoid arthritis (RA) is ideal. The objective for RA imaging at OMERACT IV was to start discussion about the problems and applicability of the current scoring methods for radiological damage and to start discussion on the challenge of new imaging techniques. The RA imaging module comprised preconference reading material, plenary sessions, small group discussions, and a plenary report of the group sessions, combined with interactive voting. The OMERACT filter guided the discussions. Priorities for further research in imaging studies were: (1) pathologies versus features on radiographs; (2) relation with longterm outcome; and (3) definition of minimum clinically important difference.