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

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.

The clinical approach to patients with inflammatory rheumatic diseases differs substantially from the approach to patients with many typical chronic diseases, such as hypertension or diabetes. Further elucidation of these differences may be informative in efforts to advance quantitative scientific patient assessment and management in rheumatic diseases, with improved patient outcomes

Radiographs present several attractive features for the assessment and monitoring of patients with rheumatoid arthritis (RA). Radiographic erosions are the closest to a pathognomonic sign in RA. Radiographs provide a permanent record of permanent damage. Excellent quantitative scoring systems have been developed by Larsen, Sharp, van der Heijde, Genant, Rau, and others. However, quantitative radiographic scoring is used only in research studies and is not included in usual treatment. Furthermore, magnetic resonance imaging and ultrasonography may be more sensitive than radiography in detecting abnormalities. Moreover, treatment of patients with RA should be initiated before evidence of damage. Reports that biologic therapy is superior to methotrexate in preventing radiographic progression are accurate for groups of patients, although methotrexate and other disease-modifying antirheumatic drugs control inflammation in 70% to 80% of patients and most patients present no radiographic progression with methotrexate. Radiographic findings are also much less significant and functional measures are far more significant in the prediction of severe outcomes of RA, including costs and mortality. Whereas prevention of radiographic progression is certainly desirable, it appears that prevention of functional disability is far more important for successful patient outcomes

In many chronic diseases, objective gold standard measures such as blood pressure, cholesterol, and bone densitometry often provide most of the information used to establish a diagnosis and guide therapy. By contrast, in inflammatory rheumatic diseases, information from a patient history usually is considerably more prominent in clinical management. Patient history data can be recorded as standardized, quantitative scientific data through use of validated self-reported questionnaires. Patient questionnaires address the primary concerns of patients and their families. Questionnaire scores distinguish active from control treatments in clinical trials at similar levels to swollen and tender joint counts or laboratory tests. Patient questionnaire data are correlated significantly with joint counts, radiographic scores, and laboratory tests, but usually are far more significant than these measures in the prognosis of severe outcomes of rheumatoid arthritis (RA), including work disability, costs, and premature death. Limitations of patient questionnaires are based on cultural features involving variation in responses among ethnic groups, and a need for translation, although translated questionnaires can be as valuable as a translator. Patient questionnaires do not replace further medical history, physical examination, laboratory tests, and imaging data, and they require interpretation in a context of these standard sources of information at any clinical encounter. Patient questionnaires are useful to monitor patient status in usual clinical care, with almost no effort on the part of the physician and staff if distributed by the receptionist in the infrastructure of office practice

RAPID3 (routine assessment of patient index data 3) is a pooled index of the 3 patient-reported American College of Rheumatology rheumatoid arthritis (RA) Core Data Set measures: function, pain, and patient global estimate of status. Each of the 3 individual measures is scored 0 to 10, for a total of 30. Disease severity may be classified on the basis of RAPID3 scores: >12 = high; 6.1-12 = moderate; 3.1-6 = low; < or =3 = remission. RAPID3 scores are correlated with the disease activity score 28 (DAS28) and clinical disease activity index (CDAI) in clinical trials and clinical care, and are comparable to these indices in capacity to distinguish active from control treatments in clinical trials. RAPID3 on a multidimensional health assessment questionnaire (MDHAQ) is scored in 5 to 10 seconds, versus 90 to 94 seconds for a formal 28-joint count, 108 seconds for a CDAI, and 114 seconds for a DAS28. An MDHAQ can be completed by each patient at each visit in the waiting room in 5 to 10 minutes, as a component of the infrastructure of routine care, with minimal effort of the rheumatologist and staff, to provide RAPID3 scores as well as additional data including a self-report joint count, fatigue, review of systems, and recent medical history. In all rheumatic diseases RAPID3 is able to provide a baseline quantitative value, and to quantitatively monitor and document improvement or worsening over time