Rheumatoid Arthritis: Pincus T

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.

Pincus T, Yazici Y, Sokka T. · Department of Medicine, Division of Rheumatology, New York University Hospital for Joint Diseases, New York, NY 10003, USA. · Nat Clin Pract Rheumatol. · Pubmed #18461062 No free full text.

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Pincus T, Huizinga TW, Yazici Y. · No affiliation provided · J Rheumatol. · Pubmed #17304647 links to  free full text

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Pincus T, Tugwell P. · No affiliation provided · J Rheumatol. · Pubmed #17216670 links to  free full text

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Pincus T, Yazici Y, van Vollenhoven R. · No affiliation provided · J Rheumatol. · Pubmed #17143975 links to  free full text

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Pincus T. · No affiliation provided · J Rheumatol. · Pubmed #16652413 links to  free full text

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Pincus T, Sokka T. · No affiliation provided · Rheumatology (Oxford). · Pubmed #16537578 links to  free full text

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Pincus T. · No affiliation provided · Arthritis Rheum. · Pubmed #14558072 links to  free full text

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Pincus T, Gibofsky A, Weinblatt ME. · No affiliation provided · Arthritis Rheum. · Pubmed #11953958 No free full text.

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Pincus T, Sokka T, Stein CM. · No affiliation provided · Ann Intern Med. · Pubmed #11777366 links to  free full text

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Pincus T, Sokka T, Wolfe F. · No affiliation provided · Arthritis Rheum. · Pubmed #11407680 links to  free full text

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Pincus T, Wolfe F. · No affiliation provided · J Rheumatol. · Pubmed #11128653 No free full text.

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Sokka T, Abelson B, Pincus T. · Department of Medicine, Jyväskylä Central Hospital, Jyväskylä, Finland. · Clin Exp Rheumatol. · Pubmed #19026144 No free full text.

Abstract: Mortality rates in patients with rheumatoid arthritis (RA) are 1.5-1.6 fold higher than in the general population, with similar patterns over 60 years. The acute attributed causes of death appear overall similar to the general population, with cardiovascular disease the most common attributed cause of death, and with more infection, pulmonary and renal disease in RA than in the general population. All clinical measures indicating more severe clinical status appear prognostic of premature mortality, with rheumatoid factor and the shared epitope significant for progressive RA. Functional and global measures as well as comorbidities generally are the most significant predictors of premature death.

Pincus T. · New York University School of Medicine, New York, NY, USA. · Bull NYU Hosp Jt Dis. · Pubmed #18937635 links to  free full text

Abstract: A quantitative count of swollen and tender joints is a primary measure to assess patients with rheumatoid arthritis (RA), and is weighted of higher value than the other 5 Core Data Set measures in all indices in which it is included. However a number of limitations of the swollen and tender joint count have been described in the rheumatology literature, including poor reproducibility, with a requirement to be performed by the same observer at each visit; likelihood to improve with placebo treatment as much or more than the other 5 RA Core Data Set measures in clinical trials; similar or lower relative efficiencies than global and patient measures to document differences between active and control treatments in clinical trials; improvement over 5 years in clinical care, while joint damage and functional disability may progress; and lower sensitivity to detect inflammatory activity than ultrasound. Most visits to a rheumatologist do not include a formal quantitative joint count. It may be suggested that a careful qualitative joint count, supplemented by quantitative patient self-report questionnaire scores, may be more than adequate to monitor and document changes in patient status in busy clinical settings.

Sokka T, Envalds M, Pincus T. · Arkisto/Tutkijat, Jyväskylä Central Hospital, Jyvaskyla, Finland. · Mod Rheumatol. · Pubmed #18437286 links to  free full text

Abstract: Modern therapy for rheumatoid arthritis (RA) is based on knowledge of the severity of the natural history of the disease. RA patients are approached with early and aggressive treatment strategies, methotrexate as an anchor drug, biological targeted therapies in those with inadequate response to methotrexate, and "tight control," aiming for remission and low disease activity according to quantitative monitoring. This chapter presents a rationale for current treatment strategies for RA with antirheumatic drugs, a review of published reports concerning treatments in clinical cohorts outside of clinical trials, and current treatments at 61 sites in 21 countries in the QUEST-RA database.

Pincus T. · NYU Hospital for Joint Diseases, New York, 301 East 17th Street, New York, New York 10003, USA. · Bull NYU Hosp Jt Dis. · Pubmed #17708743 links to  free full text

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Pincus T, Yazici Y, Sokka T. · NYU Hospital for Joint Diseases, New York, NY 10003, USA. · Best Pract Res Clin Rheumatol. · Pubmed #17678823 No free full text.

Abstract: No single measure can serve as a 'gold standard' for the diagnosis, prognosis, and monitoring of patients with rheumatic diseases. Therefore, pooled indices of several measures have been developed for patient assessment. Quantitative measures and indices in rheumatology have been used primarily in clinical trials and other clinical research, but not in standard clinical care. Indeed, most standard rheumatology care is conducted without quantitative data other than laboratory tests, which often are uninformative. Some measures used in research have been adapted for standard care. The classical 66/68-joint count with graded scoring for swelling, tenderness, pain on motion, limited motion, and deformity has been shortened for clinical care to a 28-joint count, scored only as 'Yes' or 'No' for swelling or tenderness. Patient questionnaires designed for clinical research can be lengthy, with complex scoring, so that information is not available to help guide clinical decisions. By contrast, patient questionnaires designed for standard care, such as a simple one-page, multi-dimensional health assessment questionnaire (MDHAQ), are short, save time, are easily scored, and are useful in all rheumatic diseases to monitor patient status at each visit and document changes over long periods. More attention to measures for use in standard care could improve care and outcomes for patients with rheumatic diseases.

Pincus T. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4500, USA. · Bull NYU Hosp Jt Dis. · Pubmed #17121487 links to  free full text

Abstract: Medical care is advanced by quantitative measures, all of which have advantages and limitations. No single "gold standard" measure, analogous to blood pressure, is available for diagnosis, prognosis, and management of rheumatoid arthritis (RA). Four types of measures have been used, including joint counts, radiographs, laboratory tests, and patient questionnaires. Joint counts are the most specific measure for RA but are poorly reproducible and not performed in most standard care. Radiographs provide an objective record of joint damage, but are scored quantitatively only in clinical research and have little prognostic value for long-term outcomes such as work disability and mortality. Laboratory tests are helpful when positive but frequently are "false negative"--for example, rheumatoid factor (RF), erythrocyte sedimentation rate, or C-reactive protein are normal in 30% to 45% of patients. "False positive" results are also seen; most people with RF or antinuclear antibody do not have a disease. Patient questionnaires are useful to assess and monitor patient status and provide the most significant predictive measures for long-term work disability and mortality. A multidimensional health assessment questionnaire is useful in all rheumatic diseases, with scoring templates and medical history information to save time for the rheumatologist and patient in standard care.

Pincus T, Kavanaugh A, Aletaha D, Smolen J. · Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #17083755 No free full text.

Abstract: The rheumatology community has devoted increasing attention to the subject of remission over the past 2 decades, on the basis of greater appreciation of the long-term severity of inflammatory rheumatic diseases and availability of new therapies and approaches to improve outcomes. Nonetheless, description of remission in rheumatic diseases is complex, compared to many nonrheumatic diseases. Recognition of remission requires a set of measures or an index rather than a single "gold standard." Spontaneous remission is not infrequent in people with early inflammatory arthritis, including some who may meet criteria for rheumatoid arthritis (RA) over less than a few months, and may be confused with a drug-induced remission. Remission may be transient in many patients over short periods, and the length of time required to maintain remission status varies in different reports. Maintenance of a state of remission in autoimmune diseases that result from dysregulatory processes, rather than invasion of foreign cells or toxins, generally requires ongoing therapy indefinitely. Patients who have organ damage or functional disability may be described as "in remission," although they are free of disease activity only, but not necessarily free of disease consequences. A status of "low disease activity" or "near remission" with 70% to 90% of the features of an ideal remission may be adequate for many people with rheumatic diseases to avoid risks that may be required to reach 100% remission status. Thus, the subject of remission remains under active discussion in the rheumatology community.

Chung CP, Thompson JL, Koch GG, Amara I, Strand V, Pincus T. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232-4500, USA. · Ann Rheum Dis. · Pubmed #16504992 No free full text.

Abstract: OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.

Pincus T. · Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, 203 Oxford House, Box 5, Nashville, TN 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #16273794 No free full text.

Abstract: Pooled indices of several measures have been developed to assess and monitor patients with rheumatoid arthritis in clinical trials and clinical care, as no single measure can serve as a "gold standard" in all individual patients. Early indices of disease activity include the Steinbrocker "therapeutic scorecard in rheumatoid arthritis," the Lansbury Index, and Paulus criteria. The most widely used indices at this time are the American College of Rheumatology (ACR) Core Data Set and disease activity score (DAS). A simplified disease activity index (SDAI) and clinical disease activity index (CDAI) are derived from the DAS. The ACR Core Data Set includes 7 measures--swollen joint count, tender joint count, patient assessment of global status, an acute phase reactant [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)], health professional assessment of global status, physical function, and pain; the first four of these measures are included on the DAS. Improvement criteria for the ACR Core Data Set are based on improvement of at least 20% in both tender and swollen joint counts, and three of the five additional measures (ACR 20), and corresponding "ACR 50," and "ACR 70." A pooled index which includes only the three patient self-report questionnaire measures from the Core Data Set, physical function, pain, and patient assessment of global status performs as well as ACR 20 or DAS to discriminate between efficacy of active versus placebo treatment in a clinical trial.

Sokka T, Pincus T. · Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 203 Oxford House, Box 5, Nashville, TN 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #16273786 No free full text.

Abstract: A count of swollen and tender joints is the most specific quantitative clinical measure to assess and monitor the status of patients with rheumatoid arthritis. Many methods have been described to quantitate joint abnormalities, including scoring various numbers of joints (with or without grading of abnormality) for different types of abnormalities, including swelling, tenderness, pain on motion, limited motion, and deformity. This article reviews selected methods for the performance of joint counts, with discussion of their advantages and limitations in the assessment of patients with rheumatoid arthritis.

Pincus T, Sokka T. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, 203 Oxford House, Box 5, Nashville, TN 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #16273778 No free full text.

Abstract: Quantitative measurement has led to major advances in the diagnosis, prognosis and management of chronic diseases. Quantitative measures in rheumatic diseases differ from measures in many chronic diseases in several respects. There is no single "gold standard," such as blood pressure or cholesterol, in the diagnosis, management, and prognosis of any rheumatic disease. Laboratory tests are limited; for example, in rheumatoid arthritis > 40% of patients or more have a normal erythrocyte sedimentation rate (ESR). Formal joint counts have poor reliability and are not performed at most visits of most patients. Radiographs are rarely read quantitatively, except in formal clinical trials. The optimal quantitative measures to monitor status and assess long-term prognosis are often derived from patient self-report questionnaires. Quantitative measures may reflect disease activity, e.g., swollen joint counts or C-reactive protein (CRP), long-term damage, e.g., radiographic damage, or poor outcomes, e.g., work disability and premature death. Disease activity measures used in clinical trials are primarily surrogates for long-term outcomes. As there is no single "gold standard" measure, indices of multiple measures are used in patient assessment. Indices used in rheumatoid arthritis assess primarily disease activity, but separate indices have been developed to assess disease activity versus damage in patients with ankylosing spondylitis, systemic lupus erythematosus, and vasculitis.

Pincus T, Sokka T, Kavanaugh A. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #15552515 No free full text.

Abstract: Therapies for rheumatoid arthritis (RA) may be assessed according to relative levels of measures to compare efficacy to another therapy or to a placebo, as in the American College of Rheumatology (ACR) 20%, 50%, or 70% (ACR 20 ACR 50 and ACR 70) responses, or by absolute levels of measures, as in disease activity scores (DAS), ACR criteria for remission, or "target values" of specific measures. Regulatory considerations have emphasized primarily relative comparisons to a placebo or standard therapy, derived in part from the weak efficacy of traditional disease modifying anti-rheumatic drugs (DMARDs). While improvement compared to placebo certainly indicates efficacy, it is of concern that measures of inflammatory activity, such as swollen joints and the erythrocyte sedimentation rate (ESR), may be stable or improved over periods of 5-10 years, while measures of damage, such as joint deformity and radiographic changes, may progress over the same period in the same patients. These findings suggest that improvement at a level of 20% or 50% may deter but not prevent severe long-term outcomes of radiographic progression, functional declines, work disability, and premature mortality, seen in most patients until the middle 1990s. Outcomes appear to be improved at this time, associated with aggressive treatment strategies and more powerful therapies, including biologic agents. In the Finnish Rheumatoid Arthritis Combination Therapy Trial (FinRACo), no patient who was in remission after 6 months was receiving work disability payments 4 1/2 years later, compared to 22% of patients who had ACR 20 or 50 responses and 54% of patients who did not have ACR 20 responses after 6 months who were all receiving work disability payments after 5 years. These findings suggest that absolute targets, including remission, may be realistic contemporary goals, with aggressive treatment strategies and more effective DMARDs and biologic agents.

Pincus T, Sokka T, Kavanaugh A. · Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-4500, USA. · Clin Exp Rheumatol. · Pubmed #15552511 No free full text.

Abstract: Assessment of benefit/risk of therapies for any disease is best conducted according to quantitative data. In many diseases, such as hypertension or hyperlipidemia, a single quantitative measure serves as a "gold standard" for patient status, but no single measure can serve as a "gold standard' for all individual patients with rheumatoid arthritis (RA). Therefore, indices such as the American College of Rheumatology (ACR) Core Data Set and Disease Activity Score (DAS), are used in clinical trials and other clinical research. These indices include 3 types of measures, which are derived from a health professional [joint counts, global]; a laboratory [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]; or a patient questionnaire [physical function, pain, global]. In most standard clinical care, the majority of clinicians do not collect joint count or patient questionnaire data at most visits. Therefore, assessment and management of most patients with RA is conducted empirically, with the only quantitative data from laboratory tests. Measures on a patient self-report questionnaire of physical function, pain, and global status, are as informative as joint counts, radiographic scores, laboratory tests, or any measure by a health professional to document status, estimate prognosis, and monitor responses to therapies. We suggest that quantitative measurement may be incorporated into standard clinical care most easily and effectively by asking each patient to complete a simple 1-page questionnaire at each visit to a rheumatologist.