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T Pincus

Publications and source records attributed to T Pincus.

At least 235 records · Page 13Linked to original sources

Use of combination therapy in the routine care of patients with rheumatoid arthritis: physician and patient surveys.

AIMS: To describe the utilization of combination therapy in the treatment of rheumatoid arthritis (RA). METHODS: Review of published articles and abstracts, and patient/physician questionnaire data. RESULTS: Combination therapy was rarely used in the early 1980s and is now (1999) used for about 25% of RA patients in the US. Physician and patient surveys indicate that methotrexate plus hydroxychloroquine is the most commonly used combination in North America, and physician surveys indicate that methotrexate plus sulfasalazine is the most commonly used combination in Europe. Patient questionnaire data indicate that 13.4% of patients in the US take methotrexate and hydroxychloroquine, and between 11% and 15% of patients with recent onset of RA receive treatment with disease-modifying antirheumatic drug (DMARD) combinations. CONCLUSIONS: Combination therapy with agents such as hydroxychloroquine and methotrexate is used in up to 25% of RA patients in the US, but the use of "aggressive combination therapy" is unusual. Whether combination therapy as currently practiced is beneficial remains to be determined.

Antirheumatic Agents↗

Mortality, course of disease and prognosis of patients with ankylosing spondylitis.

Patients with ankylosing spondylitis (AS) have about a 50% increased risk of mortality on the basis of the limited amount of data available. There is some evidence that the progression of disease is strongest in the first 10 years of disease but it is also clear that the disease keeps on being active for further decades. The overall burden of disease is similar to rheumatoid arthritis but the overall disease duration of AS is longer. Prognostic factors have also not been studied extensively in AS but it seems clear that early hip involvement indicates a worse outcome. The same is true for early limitation of spinal mobility, laboratory evidence of ongoing disease activity (ESR, hypergammaglobulinemia), peripheral arthritis and dactylitis. The significance of organ involvement for the prognosis, especially in the kidney in the form of amyloidosis, and in the heart and lungs, is less clear. Radiation therapy of the spine, which had been performed quite extensively in former decades, has been associated with a mean radiation dose of about double that of atomic bomb survivors and an increased risk of leukemia and mortality. This therapy has been largely abandoned nowadays. Elder rheumatologists report however that the clinical improvement of irradiated patients has been partly impressive.

Hip Joint↗

A historical perspective concerning population-based and clinical studies of early arthritis and early rheumatoid arthritis.

Research concerning early arthritis and early rheumatoid arthritis (RA) may be considered to have begun with population-based studies in the United Kingdom, the United States and Scandinavia, from the late 1950s to the late 1960s. These studies indicated that the majority of people with clinical findings of RA had no evidence of disease 3-5 years later, and that only about 25% to 30% of people in a population who met the criteria for RA had rheumatoid factor. These findings may have contributed to an underestimation of RA until the severity of long-term outcomes of clinical RA were recognized in the 1980s on the basis of clinical cohorts. The first major early RA clinical cohort was established in 1957-1963 in Bath, England. Although results at 3 and even 11 years were not overly unfavorable, by 15 and 20 years most patients had severe outcomes of functional declines and premature mortality. The Middle-sex (UK) early RA cohort established in 1966-1971 indicated that radiographic abnormalities were observed in about 70% of patients by 2 years of disease, and were seen in most patients initially in the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971 suggested that a progressive course of RA is predicted by a higher number of involved joints at baseline. The Lund (Sweden) early RA cohort established in 1985-1989 indicated rather severe long-term outcomes in patients treated according to traditional conservative approaches to use of disease modifying anti-rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National Health Service trusts in the UK was established in 1987-93, and showed associations of education level and socioeconomic status with clinical status. The movement towards early arthritis clinics was given great impetus following the work by Emery in the early 1990s. These studies and others described elsewhere in this supplement have contributed to the foundations for the clinical approach to early arthritis in the 21st century.

Adult↗

Uniform databases in early arthritis: specific measures to complement classification criteria and indices of clinical change.

Rheumatoid arthritis (RA) is not characterized by a single pathognomonic measure such as blood pressure in hypertension or cholesterol in hyperlipidemia, which can be used in the diagnosis, prognosis, and monitoring of patient status. Measures such as swollen joints and an elevated erythrocyte sedimentation rate are certainly valuable, but many individuals with abnormal values have conditions other than RA, and many people with RA may have favorable values for one or more of these measures. Therefore, the rheumatology community has developed indices of several measures, such as classification criteria, the disease activity score (DAS), and the ACR Core Data Set with 20%, 50% and 70% improvement (ACR 20, ACR 50, ACR 70) to classify and monitor patients with RA. While these indices have greatly advanced clinical research, databases for long-term observations, including those in early RA described in this Supplement, differ in 20-50% of included data, and the software platforms for these databases differ sufficiently to render it difficult to merge the data to compare one data set to another. It has been proposed that a uniform database for early arthritis clinical research could help advance clinical research in early arthritis. One example of such a database, termed a "standard protocol to evaluate rheumatoid arthritis" (SPERA), has been in use for almost two decades in one clinical site, and has proven valuable in a number of ways, including the demonstration of early radiographic damage, development of a 28-joint count, and documentation that patient questionnaire data are correlated significantly with laboratory, joint count and radiographic data, although questionnaire data are the strongest predictors of severe outcomes including work disability and premature mortality. The use of a uniform database in no way precludes the collection of additional data at particular centers including immunogenetic, serologic, or structural magnetic resonance imaging (MRI) data. However, the availability of an infrastructure of standard data in all RA databases would enhance clinical research in early RA.

Adult↗

Databases of patients with early rheumatoid arthritis in the USA.

Several databases of patients with early rheumatoid arthritis (RA) have been established in the USA. The University of Tennessee at Memphis Cohort was organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset of < or = 6 months who met the 1958 American Rheumatism Association (ARA) criteria for at least probable RA. Two important observations from this database were that many patients seen within the first 6 months of meeting the criteria for probable RA have a self-limited rather than progressive disease, and that progressive disease is predicted by a high number of baseline swollen and tender joints. The National Institutes of Health (NIH) cohort of patients with peripheral synovitis for > or = 6 weeks but < 12 months in at least one peripheral joint was established in 1994. At the one-year follow-up, 45% of the patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated arthritis. The number of active joints, rather than meeting the criteria for RA, was the primary determinant of function and performance after one year. The Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or = 6 swollen and > or = 9 tender joints, and no previous treatment with disease modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the validity of self-report joint counts. American College of Rheumatology 20% improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57% of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of patients prior to the availability of biologic agents. The North American Cohort of Patients with Early RA (SONORA), which included patients with symptoms for > 3 but < 12 months, indicated that methotrexate (MTX) was the most frequently prescribed DMARD, being taken by more than half the patients. The Consortium for the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA repository has enrolled 123 African-American patients with early RA of less than 2 years' duration to analyze genetic and non-genetic factors associated with disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients with early RA (< 3 years) was established in 2001. In this registry, MTX was the first DMARD used in 83% of patients, and most patients would not meet the criteria for inclusion in recent clinical trials of biological agents. Further observation of recent cohorts of patients with early RA over the next decade should be informative regarding whether aggressive intervention strategies and new DMARDs and biologic agents lead to improved long-term outcomes.

Adolescent↗

Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis.

The two major advances over the 1990s in the treatment of rheumatoid arthritis (RA) were a shift in strategy from a "pyramid", in which disease modifying anti-rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive use of DMARDs and widespread acceptance of methotrexate as the DMARD with the most long-term effectiveness and safety. Methotrexate courses are continued far longer than those of any other DMARD, an excellent indicator of greater effectiveness and safety. In one recent series, methotrexate was the first DMARD used in more than 80% of patients with RA. Studies which document the superiority of combinations of methotrexate with biological agents to methotrexate monotherapy select for only a minority of contemporary patients with RA who have severe disease activity and incomplete responses to methotrexate. In one locale, only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate directly with biological agents, the biological agents have greater efficacy in patients with very severe disease, but the best results are seen in patients who take a combination of methotrexate and biologic agents. These data establish that methotrexate is the anchor drug and probably should be the first DMARD used in the majority of patients with RA at this time.

Antirheumatic Agents↗

Partial control of Core Data Set measures and Disease Activity Score (DAS) measures of inflammation does not prevent long-term joint damage: evidence from longitudinal observations over 5-20 years.

Several reports concerning outcomes of rheumatoid arthritis (RA) document that measures of inflammatory activity [such as swollen joint count, tender joint count, and acute phase reactant, which are included in the Core Data Set or Disease Activity Score (DAS)] may be stable or improved over 5-10 years, while measures of damage (such as radiographic progression and joint deformity) may show contemporaneous progression. Therefore, studies which include only improvement in measures of disease activity cannot document overall improvement in patient status over 5-10 years. Studies designed to document favorable long-term effects of therapy in RA must include, at baseline and later follow-up evaluation, measures of damage, such as a radiograph, joint deformity, comorbidities, and extra-articular disease, in addition to measures of disease activity. The one prognostic measure which appears to detect both activity and damage in RA over short, intermediate, and long periods is a disability score on a patient questionnaire, which might be used by all rheumatologists at all patient encounters. The need for inclusion of accurate and relevant measures of damage appears of particular importance in the current era of biological drugs, in which the slowing or prevention of damage now appears a realistic goal in most patients with RA.

Antirheumatic Agents↗

Further clues to recognition of patients with fibromyalgia from a simple 2-page patient multidimensional health assessment questionnaire (MDHAQ).

OBJECTIVE: To analyze quantitative scores for pain, fatigue, functional disability, and the number of symptoms on a review of systems on a multidimensional health assessment questionnaire (MDHAQ), including the ratios of scores for pain to physical function and fatigue to physical function, and to further study how these scores can help to identify patients with fibromyalgia. METHODS: All consecutive patients seen at a rheumatology clinic completed a 2-sided, 1-page MDHAQ at each visit to assess physical function, pain, fatigue, global status, helplessness and review of systems, and had their erythrocyte sedimentation rate (ESR) measured. Scores for these variables were analyzed in 78 consecutive patients with fibromyalgia over a two-year period, and in 149 patients with rheumatoid arthritis (RA) as a "control" group. A subset analysis was conducted in patients with RA who were classified independently according to clinical criteria as having or not having coexistent fibromyalgia. Descriptive statistics, logistic regression, and receiver-operating-characteristic curves were computed for patients with fibromyalgia and compared to patients with RA. RESULTS: Patients with fibromyalgia had high ratios of pain:physical function and fatigue:physical function scores, and a high number of reported symptoms. These quantitative data differed significantly from patients with RA. Patients with fibromyalgia also had a lower ESR than patients with RA, whose scores were similar whether or not there was coexistent fibromyalgia. Patients with fibromyalgia were distinguished equally well from patients with RA by patient questionnaire data as by the ESR. CONCLUSION: A simple 1-page, 2-sided patient questionnaire provides quantitative information which may contribute to identify patients with fibromyalgia, including patients with RA who may also have coexistent fibromyalgia.

Blood Sedimentation↗

Benefit/risk of therapies for rheumatoid arthritis: underestimation of the "side effects" or risks of RA leads to underestimation of the benefit/risk of therapies.

Most physicians are familiar with the side effects or risks of drugs used to treat rheumatoid arthritis (RA), but relatively less familiar with the "side effects" or risks associated with RA itself RA is not thought to have the same potential severity as a cardiovascular or neoplastic disease by most physicians, the public, or even some rheumatologists, although relative rates of predicted mortality in some patients with RA are in the range of some people with coronary artery disease or Hodgkin's disease. Many reasons may be identified to explain why the risks of RA have been underestimated: RA does not lead to acute life-threatening situations; population-based data have suggested that most people who meet criteria for RA have a mild or self-limited process; acute attributed causes of death in people with RA are superficially similar to those in the general population; clinical trials have suggested many therapies that are efficacious over a period of 3-12 months; few long-term longitudinal studies were performed prior to the 1980s; medical recommendations made during the 1950s-1980s suggested that simple therapies were adequate for most patients; and quantitative information concerning patient status is generally not included in standard rheumatology care. As more information has emerged concerning severe long-term outcomes in the "natural history" of RA (as treated prior to the 1990s), new strategies of aggressive intervention have been developed. Furthermore, basic research has led to new therapies. It appears that the benefit/risk ratio of therapies for RA has increased substantially over the last two decades, and the outlook for patients with RA is much better at this time than in previous years.

Antirheumatic Agents↗

Quantitative documentation of benefit/risk of new therapies for rheumatoid arthritis: patient questionnaires as an optimal measure in standard care.

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.

Antirheumatic Agents↗

Relative versus absolute goals of therapies for RA: ACR 20 or ACR 50 responses versus target values for "near remission" of DAS or single measures.

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.

Antirheumatic Agents↗

Complexities in the quantitative assessment of patients with rheumatic diseases in clinical trials and clinical care.

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.

Clinical Trials as Topic↗

Development of a multi-dimensional health assessment questionnaire (MDHAQ) for the infrastructure of standard clinical care.

The HAQ has become the pre-eminent patient questionnaire used in rheumatology. It is easily completed by patients, but not easily reviewed and scored in standard clinical care and has some minor psychometric limitations, as do all questionnaires. Modifications of the HAQ been made to facilitate use in standard care, particularly to include 8-10 activities of daily living, along with scores for pain and global status and other information on one side of one page for rapid review by the clinician. A patient questionnaire for standard care should be limited to 2 sides of 1 page, in a format amenable to "eyeball" review by the clinician in 5 seconds or less. It can be scored formally in 15-20 seconds or less, and is useful in patients with all rheumatic diseases. The current version of a multi-dimensional HAQ (MDHAQ) includes scoring templates on the questionnaire to allow formal scoring in less than 15 seconds by a rheumatologist or an assistant, for possible entry onto a paper and/or computerized flow sheet. Various versions of the MDHAQ may also include a "constant" region of physical function, pain and patient global status, and "variable" regions of fatigue, morning stiffness, psychological distress, change in status, a review of systems, a rheumatoid arthritis disease activity self-report joint count (RADAI), review of recent health events, and review of medications. The MDHAQ can be used in the infrastructure of rheumatology care to include quantitative data in standard care of all patients with all rheumatic diseases.

Humans↗

Quantitative joint assessment in rheumatoid arthritis.

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.

Arthritis, Rheumatoid↗

Rheumatology function tests: quantitative physical measures to monitor morbidity and predict mortality in patients with rheumatic diseases.

Physical measures of functional status, including grip strength, walking time and button test, had been used in rheumatology clinical trials for many years, but have been supplanted in recent years by patient questionnaires. While patient questionnaire measures involve minimum professional time and have greater predictive value than physical measures for severe long-term outcomes of rheumatoid arthritis (RA), physical measures bypass socio-cultural differences which may be seen in use of patient questionnaires. Inter-observer and intra-observer reliabilities of these physical measures were excellent when administered according to a standard protocol for instructions. Physical measures of function also were significant predictors of mortality in two cohorts of patients with RA, one monitored between 1973 and 1988, and a second between 1985 and 1990.

Arthritis, Rheumatoid↗