Faculty Bibliography

Purpose: To analyze agreement levels between patient (PT) and physician (MD) assessments in 50 patients with SLE seen in usual care, including a) global PT and MD estimates of status; b) patient self-report scores on the SLAQ (Systemic Lupus Activity Questionnaire) and MDHAQ (Multidimensional Health Assessment Questionnaire) for physical function (FN), pain (PN), patient global estimate (PTGL), fatigue (FT), RAPID3 (FN, PN, and PTGL), and review of systems checklist (SX); c) physician-scored indices SLEDAI-2K (SLE Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), SLAM (SLE Activity Measure) and ECLAM (European Consensus Lupus Activity Measurement). Methods: A cross-sectional study was performed in 50 consecutive SLE patients of one rheumatologist. Patients completed the SLAQ and MDHAQ, including PTGL. The rheumatologist scored a physician global estimate (MDGL) (scored 0-3 in 0.1 increments) without knowledge of PTGL, and completed the SLEDAI 2K, BILAG, SLAM, and ECLAM. Agreement levels of various measures were analyzed using Spearman rank order correlations. Results: The study included 45 women and 5 men, mean age 38.7 years, mean disease duration 7.3 years, 36% Caucasian, 18% Black, 26% Hispanic, 18% Asian. The mean MDGL (1.10+/-0.62), PTGL (3.11 +/-2.81) and SLE indices (SLEDAI 5.02+/-3.75; BILAG 4.60+/-4.31; SLAM 3.86+/-2.92; ECLAM 1.97+/-1.37) indicated mild/moderate lupus activity. The correlation between MDGL and PTGL of rho=0.14 was not statistically significant. Correlations between MDGL and SLE indices were significant, rho=0.60-0.72 (p<0.001). Correlations between PTGL and patient measures also were significant, rho=0.58-0.87 (p<0.001). However, PTGL was correlated at lower levels with SLE indices - significantly with BILAG and SLAM (0.35-0.40; p<0.01), and not significantly with SLEDAI or ECLAM. MDGL was not correlated significantly with any patient measure or index. (Table Presented) Conclusion: MDGL and PTGL are not correlated significantly, an observation made previously. MDGL was correlated significantly with all physician-derived indices, and PTGL was correlated significantly with all patient-derived measures and indices. By contrast, MDGL was correlated at much lower, nonsignificant levels with patient-derived measures and indices, and PTGL was correlated at lower levels with physician-derived indices. Further analysis of these discordances may clarify the clinical relevance of various measures in clinical trials, and may lead to improved care and compliance in patients with SLE

Purpose: Early and aggressive treatment of RA has been associated with improved outcomes. The objective of the Rapid Onset and Systemic Efficacy (ROSE) study was to assess the efficacy of tocilizumab (TCZ) versus placebo in combination with DMARDs in reducing signs and symptoms during 24 weeks of treatment in patients with moderate to severe RA who have had inadequate clinical response to DMARDs. Methods: 619 patients were randomly assigned to TCZ 8 mg/kg + DMARDs (TCZ, n=412) or placebo + DMARDs (control, n=207). The primary efficacy end point was ACR50 response at week 24. Efficacy parameters were assessed every 4 weeks through week 24. Disease activity was also assessed at 1 week for a subset of 62 patients. Safety and laboratory parameters were assessed throughout the study. Results: Most patients were female (81%) and Caucasian (81%); mean age was 55 y, mean disease duration was 8.6 y, mean number of previous DMARDs was 1.2, and mean DAS28 was 6.5. At week 24, there was a significantly higher percentage of ACR50 responders (primary end point) in the TCZ group than in the control group (30.1% vs 11.2%; p<0.0001). Significantly higher percentages of patients in the TCZ group than in the control group achieved ACR20 and ACR50 responses from week 4 through week 24 and ACR70 responses from week 8 through week 24 (Table). Patients in the TCZ group had significant improvement in RAPID3 scores from week 4 through week 24 and in FACIT-Fatigue scores from week 8 through week 24 compared with control (Table). In the TCZ group, improvements in CRP and Hb levels occurred early (week 4) and were sustained through week 24; CRP improvement was significant at all time points (p<0.0001). In the subset, DAS28 and patients' pain and global assessment scores significantly improved, and CRP levels normalized 1 week after TCZ treatment (p<=0.01 vs control). SAE rates/100 PY (95% CI) were 24 (17, 33) and 19 (11, 31) for the TCZ and control groups, respectively. Serious infections were reported in 2.9% and 0.5% of patients in the TCZ and control groups, respectively. Malignancies were reported in 0.7% and 1.5% of patients in the TCZ and control groups, respectively. ALT shifts from normal at baseline to >3x ULN occurred in 3.2% of TCZ patients and in 1.1% of control patients. Clinically significant (grade 3/4) decreases in neutrophil counts were reported in 2.9%/0% of TCZ patients; no grade 3/4 decreases were reported in control patients. There were no occurrences of decreased platelet counts to clinically significant values (grade 3/4). Conclusions: TCZ led to significant improvements in disease activity, ACR responses, and CRP and Hb levels as early as week 4 and in DAS28 response as early as week 1; responses persisted through week 24. Safety findings were consistent with the known safety profile of TCZ. With early and sustained efficacy, TCZ is an effective treatment option for patients with RA who have failed DMARDs. (Table Presented)

Background: Ocular disease has been reported in up to 75 % of patients with Behcet's Syndrome (BS) in endemic regions where permanent visual loss is common. The prevalence of eye disease in North American BS patients is unknown, but felt to be lower than in endemic regions. More prevalent and severe eye disease is expected in North American populations with an ethnic background in those regions. Methods: A BS center was established in New York City in 2004. Patients at the center completed an MDHAQ, BSAS (Behcet Syndrome Activity Score), questionnaires about past medical history, medication use, Behcet's specific history, ethnic and demographic information. These data were prospectively collected over 5 years and updated on each visit. Patients fulfilling the International Behcet's Classification Criteria were analyzed as one cohort and then in 2 groups: Group A= with ethnic background in northern/central Europe and North America and/or self declared Caucasians without Mediterranean, Middle Eastern and/or Far Eastern background; Group B= Patients with Mediterranean, Middle Eastern, North African, or Far Eastern ethnic background. These groups were compared for their prevalence, type and outcome of ocular disease. Results: 471 patients were seen for suspected BS. 296 (62.8%) fulfilled the International Behcet's Classification Criteria and were included in the present study. Of those, 121 (40.9%) patients had eye disease, which included 56 (18.9%) with uveitis, 8 (2.7%) with retinitis, 11 (3.7%) with episcleritis, and 42 (14.2%) with other eye disease. There was no statistically significant difference between Groups A (n=163) and B (n=133) regarding the prevalence of eye disease (41.1% vs. 40.6%, p<0.93), types of involvement: uveitis (19.6% vs. 18.0%, p<0.729), retinitis (1.8% vs. 3.8%, p<0.311), episcleritis (3.1% vs. 4.5%, p<0.514), baseline disease activity and use of immunosuppressive medications. None of the patients presented with or developed blindness during the study period. Conclusions: Eye involvement was less prevalent and seemed to have better outcomes in this North American cohort of BS patients than in cohorts studied in high-incidence/endemic BS regions. Contrary to our expectations, there was no significant difference in prevalence or outcome of Behcet's eye disease between North Americans of non-Mediterranean European ancestry compared to individuals of Mediterranean, Middle- or Far Eastern descent living in the US. These findings could suggest a role of environmental factors in the phenotypic expression of BS in general, and in the pathogenesis of Behcet's eye disease in particular

Purpose: To evaluate the correlation of patient vs physician reported outcome measures in a routine care SLE cohort. Methods: The first recorded physician global observations in patients with the primary diagnosis of systemic lupus were identified; corresponding demographic, patient reported functional outcomes and current usage of prednisone, hydroxychloroquine and non-steroidal anti-inflammatory medications and immunosupressive medication use were abstracted. Current medication usage was operational defined as medications taken prior to and including the visit date; patient discontinuations prior to the selected visit and medication initiations at the selected visit were defined as non-current usage. Summary statistics for demographic, outcome

The treatment of rheumatoid arthritis has changed over the last 15 years. Early and aggressive treatment, use of methotrexate as the anchor drug and combination treatment, with older disease-modifying drugs or biologics, have become the norm. TNF inhibitors were the first biologic agents available to rheumatologists and are still currently used as first-line biologics, in addition to other newer biologic agents. Abatacept, rituximab and tocilizumab are available biologics that use a different mode of action to TNF inhibitors, and can be used after a TNF inhibitor is tried. Abatacept is also currently used as a first-line biologic and others can also be used once data are available

OBJECTIVE: Studies have suggested that early institution of tumor necrosis factor (TNF) inhibitors improves functional status and slows radiographic progression among patients with rheumatoid arthritis (RA). To determine whether these findings have altered practice patterns, we used the Consortium of Rheumatology Researchers of North America (CORRONA) registry to assess the pattern of TNF inhibitor utilization in the US over time. METHODS: Demographics and disease activity data were collected for patients with RA. The trend of TNF inhibitor use during 2002-06 was evaluated prospectively using linear and logistic regression models. RESULTS: Of the 11,397 patients with RA, 66% and 34% had established RA and early RA (disease duration < 3 yrs), respectively. The majority of patients were female and Caucasian. Despite comparable levels of disease activity, more of the patients with established RA were taking TNF inhibitors than those with early RA (40% vs 25%; p < 0.0001). The majority of patients (70%) taking TNF inhibitors were also receiving disease modifying antirheumatic drugs. The use of TNF inhibitors increased at a rate of 2.8% per year in established RA and 1.2% per year in early RA. The mean Clinical Disease Activity Index at the start of TNF inhibitors decreased at a rate of -0.233 per quarter (p = 0.006), while the mean Disease Activity Score decreased at a rate of -0.04 per quarter (p = 0.022). CONCLUSION: Utilization of TNF inhibitors in this multicenter, observational US cohort is increasing in both early and established RA, although it is more prominent among patients with established RA. The level of disease activity at which TNF inhibitors were initiated decreased over time in patients with both established and early RA.

OBJECTIVE: To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. METHODS: We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). CONCLUSION: MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.

OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. RESULTS: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. CONCLUSIONS: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

ABSTRACT: INTRODUCTION: Gender as a predictor of outcomes of rheumatoid arthritis (RA) has evoked considerable interest over the decades. Historically, there is no consensus whether RA is worse in females or males. Recent reports suggest that females are less likely than males to achieve remission. Therefore, we aimed to study possible associations of gender and disease activity, disease characteristics, and treatments of RA in a large multinational cross-sectional cohort of patients with RA called Quantitative Standard Monitoring of Patients with RA (QUEST-RA). METHODS: The cohort includes clinical and questionnaire data from patients who were seen in usual care, including 6,004 patients at 70 sites in 25 countries as of April 2008. Gender differences were analyzed for American College of Rheumatology Core Data Set measures of disease activity, DAS28 (disease activity score using 28 joint counts), fatigue, the presence of rheumatoid factor, nodules and erosions, and the current use of prednisone, methotrexate, and biologic agents. RESULTS: Women had poorer scores than men in all Core Data Set measures. The mean values for females and males were swollen joint count-28 (SJC28) of 4.5 versus 3.8, tender joint count-28 of 6.9 versus 5.4, erythrocyte sedimentation rate of 30 versus 26, Health Assessment Questionnaire of 1.1 versus 0.8, visual analog scales for physician global estimate of 3.0 versus 2.5, pain of 4.3 versus 3.6, patient global status of 4.2 versus 3.7, DAS28 of 4.3 versus 3.8, and fatigue of 4.6 versus 3.7 (P < 0.001). However, effect sizes were small-medium and smallest (0.13) for SJC28. Among patients who had no or minimal disease activity (0 to 1) on SJC28, women had statistically significantly higher mean values compared with men in all other disease activity measures (P < 0.001) and met DAS28 remission less often than men. Rheumatoid factor was equally prevalent among genders. Men had nodules more often than women. Women had erosions more often than men, but the statistical significance was marginal. Similar proportions of females and males were taking different therapies. CONCLUSIONS: In this large multinational cohort, RA disease activity measures appear to be worse in women than in men. However, most of the gender differences in RA disease activity may originate from the measures of disease activity rather than from RA disease activity itself

OBJECTIVE: Patients with rheumatoid arthritis (RA) commonly switch between tumor necrosis factor (TNF) inhibitors after failing to control disease activity. Much of the clinical data that support switching to a second TNF agent when one agent fails to work has come from small, short-term studies. We utilized a US insurance claims database to determine patterns of use such as dose escalation, time to discontinuation, and switching between TNF inhibitors in patients with RA. METHODS: A retrospective analysis was performed using an insurance claims database in the US from 2000 to 2005. TNF inhibitor use, time to switch, dose escalation, and continuation times were analyzed in patients with RA. RESULTS: Nine thousand seventy-four patients with RA started TNF inhibitors during the period 2000 to 2005. Etanercept was the most commonly used TNF inhibitor; infliximab had the highest duration of continuation, about 50% at 2 years. In addition, infliximab showed higher rates of dose escalation compared to etanercept and adalimumab. For all TNF inhibitors, time to switching decreased from 2000 to 2005. CONCLUSION: TNF inhibitor use patterns changed from 2000 to 2005, with more frequent changes among the different TNF inhibitors and a shorter duration of treatment before the change. Only about 50% of TNF inhibitors are still continued at 2 years, reflecting the difference between randomized clinical trials and real-world experience