Faculty Bibliography

OBJECTIVE: The relative high cost and potential side effects mandate careful scrutiny as to when tumor necrosis factor alpha (TNF) inhibitors should be used in everyday practice. We surveyed how TNF inhibitors performed in randomized controlled trials when compared to methotrexate in methotrexate naive rheumatoid arthritis patients. METHODS: We identified all randomized controlled trials with TNF inhibitors and methotrexate. We surveyed A-whether the patients enrolled were methotrexate naive or not; B-efficacy outcomes and C-radiographic outcomes. RESULTS: Four studies that had been reported to be conducted among metho-trexate naive patients were identified. TEMPO trial was not done entirely in methotrexate naive patients, contrary to what has been reported by its authors. Among these studies the methotrexate naive arms did as well as the TNF inhibitor alone. The combination was better than either drug alone. Among the 6 studies in which the methotrexate failure patients had been enrolled, the TNF inhibitors always performed better when analyzed head to head with the methotrexate alone arms. CONCLUSIONS: Available data indicate that TNF inhibitors are superior to solo methotrexate use only in the setting of combination treatment

OBJECTIVE: To analyze the time required to score different measures used to assess patients with rheumatoid arthritis (RA), as a guide to feasibility in standard care. The measures studied were a 28-Joint Count, Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ), Multidimensional HAQ (MDHAQ), and various Routine Assessment of Patient Index Data (RAPID) scores derived from the MDHAQ. METHODS: Three rheumatologists at 3 sites performed and timed 28-joint counts in 20 different patients at each site. Each rheumatologist scored and timed identical data in 5 groups of 10 from the same 50 patients seen in standard clinical care, including 50 DAS28 indices using the DAS Website, 50 identical HAQ, and 50 identical MDHAQ from the same patients. The MDHAQ includes 10 activities self-assessed for physical function, 21 circle visual analog scales (VAS) (rather than 10 cm lines), and scoring templates on the questionnaire for physical function, patient self-report joint count and RAPID composite scores. RAPID3 includes the 3 Core Data Set measures, RAPID4 adds the self-report joint count to RAPID3, and RAPID5 adds a physician global estimate to RAPID4. RESULTS: The median number of seconds to complete a 28-joint count was 90, compared to 41.9 s for a HAQ, 9.6 s for an MDHAQ RAPID3, and 19.4 s for RAPID5. CONCLUSION: MDHAQ RAPID3 scores can be calculated in considerably less time than other RA measures, using scoring templates on the MDHAQ, to provide informative, feasible, quantitative measures for standard rheumatology clinical care

OBJECTIVES: To analyse the capacity of routine assessment of patient index data 3 (RAPID3), an index of only the three patient-reported outcome (PRO) measures in the RA Core Data Set-physical function, pain and global status-to distinguish abatacept from control treatments in two clinical trials, and to compare RAPID3 results with the disease activity score 28 (DAS28) and RAPID-based indices that add a tender or swollen joint count and/or physician/assessor global estimate of status. METHODS: Clinical trial data from AIM (Abatacept in Inadequate response to Methotrexate) and ATTAIN [Abatacept Trial in Treatment of Anti-tumor necrosis factor (anti-TNF) INadequate responders] were reanalysed. Mean values were computed at baseline, endpoint and for change between baseline and endpoint for RAPID3, DAS28 and additional RAPID indices to study whether they had greater capacity to distinguish abatacept from control therapy. RAPID4TJC adds to RAPID3 a tender joint count; RAPID4SJC, a swollen joint count; RAPID4MD, a physician/assessor global estimate; and RAPID5 adds both a tender joint count and physician/assessor global estimate. RAPID2 includes only physician/assessor and patient global estimates. RESULTS: All indices indicated significant differences of 19-28% between abatacept and control groups. Results were similar for RAPID3 of only patient measures, compared to DAS28 and other RAPID-based indices. CONCLUSION: A RAPID3 'patient-only' index, without a joint count or any measure from a health professional or laboratory, distinguishes active from control treatments in two abatacept clinical trials, at levels similar to DAS28 and to other RAPID-based indices that add physician-reported measures

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels

Vasculitic syndromes are among the most complicated diseases for primary care physicians and rheumatologists to diagnose and treat. There are a myriad of symptoms that can be mimicked by other conditions, and choice of medications can be complex. Some agents are toxic and determining which to prescribe and for how long can be a multifaceted, complex decision process. Developing new treatments and new ways of using already available therapies, while minimizing potential side effects, are of paramount importance. This review will focus on recently published data that could have an impact on the way we treat systemic vasculitis patients

BACKGROUND: Treatment of rheumatoid arthritis (RA) has shifted toward earlier and more aggressive therapy with tra- ditional disease-modifying antirheumatic drugs (DMARDs) and biologics. However, the extent to which these agents are used in current clinical practice in the United States (U.S.) has not been systematically evaluated. MATERIALS AND METHODS: This analysis of a large claims database assessed patterns of use of biologics within clinical practice in a broad U.S. population with RA. We identifed two cohorts of adults with RA using Thomson Healthcare MarketScan Research databases. Patients newly diagnosed with RA between 1999 and 2004 with 12 months or more of continuous enrollment prior to diagnosis and with 24 months or more post-diagnosis were included in one cohort. The second cohort included RA patients who appeared to be newly treated with biologic therapy and had continu- ous enrollment for 12 months or more prior to frst use of a biologic agent and 18 months or more following initial treatment. A total of 16,752 patients, newly diagnosed with RA, and 8218, new to biologics therapy, were included. RESULTS: Utilization of biologics increased from 3% of patients in 1999 to 26% in 2006. Patients initiated biolog- ics both as monotherapy (30%) and in combination with methotrexate (36%). Regimen modifcations were frequent, with a large percentage of patients requiring addition or subtraction of methotrexate. CONCLUSIONS: The use of biologics to treat RA is increas- ing, either as monotherapy or in combination with another DMARD. Modifcations to drug regimens are frequent and episodes are often of comparatively short duration

Reporting of adverse events (AEs) in randomized clinical trials (RCTs) is often lacking and with limited application in the real world, as RCTs are of short duration, include small numbers of patients, and are selective for subjects lacking in comorbid conditions. It is not surprising that new and unexpected safety concerns emerge with any new drug after it has been launched and used by many more patients. Part of the problem is inherent to the way safety data are reported in RCTs. This article focuses on some of the shortcomings of AE reporting in RCTs, especially those involving tumor necrosis factor (TNF) inhibitors. Discussion focuses on reporting of 'time-to-event' issues, use of standardized incidence ratios for comparison to normal population or disease controls, use of 'patient-years' when reporting AEs, and the problem of adequate sample size and power calculations that are lacking in safety outcome data trials

Patient assessment in rheumatology is characterized by an important paradox: many extensively-characterized quantitative measures and indices have been developed for rheumatoid arthritis (RA), psoriatic arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, vasculitis, osteoarthritis, fibromyalgia, and other rheumatic diseases. However, most regular rheumatology care is guided largely by qualitative clinical impressions, without such measures or indices or any quantitative data other than laboratory tests to assess patient status and/or quality of care. This paradox may be explained in part by regarding the development of measures primarily as clinical research activities, while viewing the application of measurements in regular clinical care as continuous quality improvement (CQI) activities. The development of measures has emphasized validity and reliability, but generally ignored feasibility and acceptability to patients and health professionals, both of which are needed for application in regular clinical care. A summary of the application of clinical measurement in patients with RA over 25 years between 1982 and 2007 at a weekly academic rheumatology clinic conducted by the senior author is presented as 20 often contemporaneous CQI cycles. These cycles include development of a user-friendly modified health assessment questionnaire (MHAQ); assessment of psychological status; monitoring of mortality outcomes; comparisons of joint counts, radiographic scores, and laboratory tests to the MHAQ; a 28-joint count; prospective study of the MHAQ to predict mortality when joint counts, radiographic scores, and laboratory tests are available; development of a multidimensional HAQ (MDHAQ) with complex activities; a fatigue scale; a self-report joint count; scoring templates; a computerized data management system; flow sheets to monitor MDHAQ status; visual analog scales as 21 circles rather than 10 cm lines; composite RAPID3 (rheumatology assessment patient index data) scores for 3 patient measures; and defining RAPID categories for high, moderate and low severity, and near remission. The latter cycles remain under study as ongoing CQI activities

Objectives: We analyzed rheumatoid arthritis (RA) patients seen in a cohort from Brooklyn, NY over the last three years to determine what percentage of patients would fulfill common inclusion criteria for RA clinical trials at any time during their care. Patients and Methods: One hundred and twenty-three consecutive patients with RA, seen between April 2001 and December 2003 by a single rheumatologist, were included. Patients were analyzed according to whether they met four common inclusion criteria in most recent RA trials, and according to the inclusion criteria for the recent anti-tumor necrosis factor alpha (anti-TNF alpha) trial involving etanercept and methotrexate in early RA (ERA trial) and the STAR (Safety Trial of Adalimumab in Rheumatoid arthritis) trial. All visits were analyzed to identify any visit where patients fulfilled the inclusion criteria. Results: When the most common inclusion criteria for RA clinical trials were applied, 3/146 (2.1%) visits and two of 72 (2.8%) patients fulfilled these criteria. The inclusion criteria for the ERA and STAR trials were met in 4/123 (3.3%) and 17/123 (13.8%) patients, respectively. Conclusion: A large majority of RA patients seen in this cohort would not have qualified for the most common RA clinical trials and the recent anti-TNFa. trials. It is timely to consider new inclusion criteria for RA clinical trials to reflect the current characteristics of most RA patients. This would increase the applicability of the results of these important and usually very expensive studies and therapies

At the present time, clinical decisions in routine rheumatology practice generally are based on qualitative impressions, rather than on quantitative data, which might lead to improved information for clinical decisions. Patient questionnaires are the quantitative tools whereby rheumatologists have to monitor their patients' health status and response to therapy. The health assessment questionnaire (HAQ) and its derivatives have been shown to be the best predictors of functional and work disability, costs, joint replacement surgery, and mortality; they are as good as and usually better predictors than joint counts, radiographs, and laboratory tests. Yet, patient questionnaires, which can be used in all rheumatic diseases including osteoarthritis, systemic lupus erythematosus, fibromyalgia, sclerodenna, and ankylosing spondylitis, are not included in routine care by most rheumatologists. Every encounter of a patient with a rheumatologist provides an opportunity to collect data. Data that are feasible to collect in clinical care provide the only way to assess quantitatively how our patients are doing. If data are not collected and recorded, an opportunity is lost forever. Rheumatologists would find it valuable to adapt questionnaires to the care they provide for all their patients, to document and improve the care they provide, and add quantitative data to standard clinical care