Rheumatoid Arthritis: Boers M

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.

Boers M. · No affiliation provided · Ann Rheum Dis. · Pubmed #19088258 No free full text.

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Boers M. · No affiliation provided · Arthritis Rheum. · Pubmed #18821696 No free full text.

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Boers M. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Nat Clin Pract Rheumatol. · Pubmed #18446137 No free full text.

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Boers M. · No affiliation provided · Rheumatology (Oxford). · Pubmed #18077485 No free full text.

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Boers M. · No affiliation provided · J Rheumatol. · Pubmed #17407225 links to  free full text

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Boers M. · No affiliation provided · Ann Intern Med. · Pubmed #16785481 links to  free full text

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Boers M. · No affiliation provided · Arthritis Rheum. · Pubmed #12847667 links to  free full text

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Voskuyl AE, Boers M. · No affiliation provided · J Rheumatol. · Pubmed #12734879 No free full text.

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Landewé RB, Boers M, van der Heijde DM. · No affiliation provided · Rheumatology (Oxford). · Pubmed #12509605 links to  free full text

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Boers M. · No affiliation provided · Rheumatology (Oxford). · Pubmed #10342618 links to  free full text

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Boers M. · No affiliation provided · Neth J Med. · Pubmed #10189780 No free full text.

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van Tuyl LH, Vlad SC, Felson DT, Wells G, Boers M. · VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #19405006 No free full text.

Abstract: OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

Keeling SO, Landewe R, van der Heijde D, Bathon J, Boers M, Garnero P, Geusens P, El-Gabalawy H, Inman RD, Kraus VB, Kvien TK, Mease PJ, Ostergaard M, Ritchlin C, Syversen SW, Maksymowych WP. · Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. · J Rheumatol. · Pubmed #17343310 No free full text.

Abstract: OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. CONCLUSION: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA.

Kirwan JR, Bijlsma JW, Boers M, Shea BJ. · Liverpool Women's Hospital, Crown Street, Liverpool, UK, L8 7SS. · Cochrane Database Syst Rev. · Pubmed #17253590 No free full text.

Abstract: BACKGROUND: Glucocorticoid use in rheumatoid arthritis (RA) is widespread. Two Cochrane Reviews have been published examining the short term clinical benefit of low dose glucocorticoids compared to non-steroidal anti-inflammatory drugs and demonstrate good short term and medium term clinical benefits. The possibility that glucocorticoids may have a fundamental 'disease modifying' effect in RA, which would be seen by a reduction in the rate of radiological progression, has been raised by several authors. OBJECTIVES: To perform a systematic review of studies evaluating glucocorticoid efficacy in inhibiting the progression of radiological damage in rheumatoid arthritis. SEARCH STRATEGY: A search of MEDLINE (from 1966 to 22 February 2005) and the Cochrane Controlled Trials Register was undertaken, using the terms 'corticosteroids' and 'rheumatoid arthritis' expanded according to the Cochrane Collaboration recommendations. Identified abstracts were reviewed and appropriate reports obtained in full. Additional reports were identified from the reference lists and from expert knowledge. SELECTION CRITERIA: Randomized controlled or cross-over trials in adults with a diagnosis of rheumatoid arthritis in which prednisone or a similar glucocorticoid preparation was compared to either placebo controls or active controls (i.e. comparative studies) and where there was evaluation of radiographs of hands, or hands and feet, or feet by any standardised technique. Eligible studies had at least one treatment arm with glucocorticoids and one without glucocorticoids. DATA COLLECTION AND ANALYSIS: Standardised data extraction obtain the mean and standard deviation (SD) of change in erosion scores over 1 year or 2 years. (Where SD for change was not given a conservative estimate was taken from baseline data.) At least two authors selected the studies and extracted the data. Radiographic erosion scores were expressed as a percentage of the maximum possible score for the method used. The results were pooled after weighting in a random effects model to provide a standardised mean difference (SMD). MAIN RESULTS: The initial search produced 217 citations, and 15 were added from experts, abstracts and review of reference lists. Authors of 4 trials being prepared for publication (and subsequently published) kindly shared their data. After application of eligibility criteria 15 studies and 1,414 patients were included. The majority of trials studied early RA (disease duration up to 2 yrs), and the mean cumulative dose of glucocorticoid was 2,300 mg prednisone equivalent (range 270 mg - 5,800 mg) over the first year. Glucocorticoids were mostly added to other disease modifying anti-rheumatoid drug (DMARD) treatment. The standardised mean difference in progression was 0.40 in favour of glucocorticoids (95% CI 0.27, 0.54). In studies lasting 2 years (806 patients included), the standardised mean difference in progression in favour of glucocorticoids at 1 year was 0.45 (0.24, 0.66) and at 2 years was 0.42 (0.30, 0.55). All studies except one showed a numerical treatment effect in favour of glucocorticoids. The beneficial effects of glucocorticoids were generally achieved when used in conjunction with other DMARD treatment. AUTHORS' CONCLUSIONS: Even in the most conservative estimate, the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing. There remains concern about potential long-term adverse reactions to glucocorticoid therapy, such as increased cardiovascular risk, and this issue requires further research.

Wells G, Boers M, Tugwell P, Anonymous00204. · Department of Epidemiology and Community Medicine, University of Ottawa,Ottawa, Ontario, Canada. · Clin Exp Rheumatol. · Pubmed #17083764 No free full text.

Abstract: With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. MDA is between high disease activity and remission and anyone in remission will also be in MDA. This paper summarizes the process of coming to a definition of minimal disease activity in rheumatoid arthritis. Two equivalent preliminary definitions of minimal disease activity for use as secondary outcome measures in clinical trials in RA are proposed: a core-set definition based on the WHO/ILAR core set and a DAS-based definition based on the DAS28.

Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW. · Reumatologia, Hospitais da Universidade, 3000-075 Coimbra, Portugal. · Ann Rheum Dis. · Pubmed #16107513 links to  free full text

Abstract: Adverse effects of glucocorticoids have been abundantly reported. Published reports on low dose glucocorticoid treatment show that few of the commonly held beliefs about their incidence, prevalence, and impact are supported by clear scientific evidence. Safety data from recent randomised controlled clinical trials of low dose glucocorticoid treatment in RA suggest that adverse effects associated with this drug are modest, and often not statistically different from those of placebo.

Dijkmans BA, van Schaardenburg D, van der Horst-Bruinsma IE, Reesink HW, Vandenbroucke JP, Boers M. · VU Medisch Centrum, afd. Reumatologie, Postbus 7057, 1007 MB Amsterdam. · Ned Tijdschr Geneeskd. · Pubmed #15819133 No free full text.

Abstract: In some conditions e.g. osteoporosis, hypertension and hypercholesterolaemia, certain phenomena precede manifestation of the disease and preventive measures can be taken long before the disease presents itself. In the same way systemic lupus erythematosus (SLE) and rheumatoid arthritis can be explored. Recently, studies have been published on healthy blood donors, who later developed SLE or rheumatoid arthritis, and in whom specific autoantibodies could be demonstrated. In SLE the autoantibodies are not specific enough to develop preventive strategies, but in rheumatoid arthritis in particular there are specific antibodies against cyclic citrullinated peptides (anti-CCP-antibodies) which are very specific. A clinical trial has been initiated in which HLA-DR4-positive people with raised autoantibody concentrations are given 1-2 intramuscular injections of dexamethasone with the aim of halving the antibody concentration and in the long term lowering the incidence of rheumatoid arthritis.

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.

Boers M, Dijkmans B, Gabriel S, Maradit-Kremers H, O'Dell J, Pincus T. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #15188348 links to  free full text

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Boers M. · Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Best Pract Res Clin Rheumatol. · Pubmed #15123035 No free full text.

Abstract: Treatment of rheumatoid arthritis with glucocorticoids remains controversial despite a considerable and growing body of evidence. This chapter focuses on the research agenda in urgent need of execution: to define conclusively the benefit/harm trade-offs and pin down the place of these agents in the treatment cascade.

Verhagen AP, Bierma-Zeinstra SM, Cardoso JR, de Bie RA, Boers M, de Vet HC. · Department of General Practice, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, Netherlands. · Cochrane Database Syst Rev. · Pubmed #14583923 No free full text.

Abstract: BACKGROUND: Balneotherapy (spa therapy) for patients with arthritis is one of the oldest forms of therapy. One of the aims of balneotherapy is to soothe the pain, improve joint motion and as a consequence to relieve people' suffering and make them feel well. OBJECTIVES: To perform a systematic review on the effectiveness of balneotherapy for rheumatoid arthritis. SEARCH STRATEGY: Using the Cochrane search strategy, studies were found by screening: 1) The MEDLINE CD-ROM database from 1966 to June 2002 and 2) the database from the Cochrane 'Rehabilitation and Related Therapies' Field, the Pedro database up to June 2002. Also, 3) reference checking and 4) personal communications with authors was carried out to retrieve eligible studies. Date of the most recent literature search: June, 2002 SELECTION CRITERIA: Studies were eligible if they were randomised controlled trials (RCTs) comparing balneotherapy with any other intervention or with no intervention.Included participants all suffered from definite or classical rheumatoid arthritis (RA) as defined by the American Rheumatism Association Criteria (ARA) or by the criteria of Steinbrocker. At least one of the WHO/ILAR core set of endpoints for RA clinical trials had to be among the main outcome measures. DATA COLLECTION AND ANALYSIS: The Delphi list was the criteria list used to assess the components of methodological quality. Two reviewers carried out quality assessment and data extraction of the studies. Disagreements were solved by consensus. MAIN RESULTS: Six trials, representing 355 people, were included in this review. Most trials reported positive findings (the absolute improvement in measured outcomes ranged from 0 to 44%), but were methodologically flawed to some extent. A 'quality of life' outcome was reported by two trials. None of the trials performed an intention-to-treat analysis and only two performed a comparison of effects between groups. Pooling of the data was not performed; because of heterogeneity of the studies, multiple outcome measurements, and the overall data presentation was too scarce. REVIEWER'S CONCLUSIONS: One cannot ignore the positive findings reported in most trials. However the scientific evidence is insufficient because of the poor methodological quality, the absence of an adequate statistical analysis, and the absence, for the patient, of most essential outcome measures (pain, self assessed function, quality of life). Therefore, the noted "positive findings" should be viewed with caution. Because of the methodological flaws an answer about the apparent effectiveness of balneotherapy cannot be provided at this moment. A large, methodological sound trial is needed.

Wells G, Anderson J, Boers M, Felson D, Heiberg T, Hewlett S, Johnson K, Kirwan J, Lassere M, Robinson V, Shea B, Simon L, Strand V, van Riel P, Tugwell P. · Department of Clinical Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #12734920 No free full text.

Abstract: The OMERACT 6 Minimal Clinically Important Difference/Low Disease Activity Workshop was organized with the aim of meeting the many challenges that exist in determining a low disease activity in rheumatoid arthritis (RA). This article presents an overview of that workshop, including results of the voting, a summary of associated discussions, recommendations, and a proposed research agenda.

Boers M, Anderson JJ, Felson DT. · VU University Medical Centre, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #12734919 No free full text.

Abstract: This article summarizes the process proposed to come to a definition of low disease activity in rheumatoid arthritis (RA). The purpose of this definition is to aid the interpretation of trial and longitudinal study results. A conceptual proposal is "a disease activity state that is deemed a useful treatment target by both physicians and patients." An operant definition can be derived by judgmental (opinion-based) or statistical (data-based) approaches, but the first seems more appropriate. Once a few candidate definitions have been selected, their usefulness and prognostic validity can be tested in longitudinal datasets.

Wells G, Boers M, Shea B, Anderson J, Felson D, Johnson K, Kirwan J, Lassere M, Robinson V, Simon L, Strand V, van Riel P, Tugwell P. · Department of Clinical Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada. · J Rheumatol. · Pubmed #12734918 No free full text.

Abstract: The MCID (minimal clinically important difference) module of OMERACT 5 developed a research agenda that led to the conclusion that a state of low disease activity for rheumatoid arthritis (RA) would need to be defined. To develop such a definition the various concepts and terminologies, the process for developing an operational definition, and the availability and design of longitudinal datasets for validation needed to be considered. This article describes the process of the MCID/Low Disease Activity State Workshop at OMERACT 6 to develop such a definition.