Faculty Bibliography

The reporting of adverse events (AEs) in randomized clinical trials (RCTs) is often lacking in the publication of trials. Part of the problem is the way safety data are reported in RCTs. Reporting of 'time to event,' use of standardized incidence ratios for comparison to normal population or disease controls, use of 'patient years' when reporting AE, and adequate sample size and power calculations are some of the problems that need to be addressed and improved in RCTs

A guide to RAPID3 (routine assessment of patient index data), an index of three patient self-report measures-physical function, pain, and patient global estimate of status-on a multidimensional health assessment questionnaire (MDAQ) is presented, including development, scoring, use in standard care, and rationale. RAPID3 and its individual components are regarded as 'vital signs,' which may alert a health professional to unsuspected patient problems, provide a baseline measure to support a change in therapy, and numerically document improvement or worsening over time to complement clinical impressions. MDHAQ-RAPID3 can be incorporated into the infrastructure of standard rheumatology care for completion in the waiting room by every patient with any rheumatic disease at every visit: if there is a reason for a visit, there is a reason for RAPID3 vital signs. RAPID3 is calculated in 5 to 10 seconds, providing similar information to DAS28 (disease activity score) and CDAI (clinical disease activity index), which require a mean of 114 and 106 seconds, respectively. MDHAQ-RAPID3 presents an additional advantage for the patient to optimize the office encounter by completion of the questionnaire in the waiting room. The MDHAQ also includes a review of systems and recent medical history, which can save 2 to 3 minutes per visit for other patient concerns. A physician's clinical decisions ultimately require synthesis and interpretation of all available data, ranging from laboratory tests to patient questionnaire scores. RAPID3 vital signs can contribute to this synthesis toward improved quality, outcomes, and documentation of rheumatology care

Necrotizing vasculitis continues to be a condition where difficult diagnostic and treatment decisions need to be made, with only a few well-done studies as clinical reference and support. New data suggest that both methotrexate and azathioprine may be effective agents for maintaining remission in antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis after remission is achieved with cyclophosphamide-based therapies. In addition, Behcet's syndrome appears to be more common than previously assumed and is likely more common than a combination of ANCA-associated vasculitis (AAV) syndromes

Purpose: The SDAI composite disease activity index is a stringent measure of remission1, and good correlation between SDAI states and changes in radiographic progression have been reported2. Analyses were performed to assess SDAI disease activity status and to determine the correlation between SDAI status and radiographic progression in patients (pts) with RA and an inadequate response to MTX. Methods: Pts who completed the 1-yr, randomized, double-blind period of the AIM (Abatacept in Inadequate Responders to MTX) trial (abatacept ~10 mg/kg or placebo, plus MTX)³ and had radiographs at baseline and Yr 1 were eligible for analysis (post hoc, as observed). SDAI states were assessed at Mths 3 and 12, defined as High Disease Activity (HDA; >26), Moderate Disease Activity (MDA; >11-26), Low Disease Activity (LDA; >3.3-11) or remission (<=3.3). Changes from baseline to Mth 12 in Genant-modifed Sharp total score (TS) were analysed by SDAI status attained at Mth 3. Results: 366 abatacept and 154 placebo pts were eligible for analysis. Baseline demographics were comparable between treatment groups3. At Mth 3, significantly more abatacept than placebo pts had achieved LDA; at Mth 12, the proportions of abatacept pts in LDA and remission had increased ~twofold and differences between treatment groups were statistically significant for both measures (Figs). The proportion of abatacept pts in HDA was reduced by ~45% from Mth 3 to 12; levels were significantly lower vs placebo at both time points ((Figs). In the radiographic analysis, the smallest change in TS from baseline to Mth 12 was observed in abatacept pts who achieved remission at Mth 3 (change in TS: -0.2 [n=14]); mean changes in TS were 0.63 (72), 1.1 (159) and 1.97 (104) for LDA, MDA and HDA, respectively. For placebo pts mean changes in TS were 0.73 (3), 2.75 (12), 2.26 (50) and 2.9 (81) for remission, LDA, MDA and HDA, respectively. Changes in TS, especially in the remission and LDA groups, were numerically smaller in abatacept vs placebo pts. Conclusion: A significant proportion of abatacept pts achieved LDA or remission vs placebo over 1 yr according to the stringent SDAI criteria. SDAI remission and LDA at Mth 3 were associated with low levels of radiographic progression at Mth 12, in particular with abatacept compared with placebo, suggesting that these states are predictive of a reduction in radiographic progression, as observed with other biologics⁴

Purpose: Behcet syndrome (BS) is a systemic vasculitis that is common in the old Silk Route but rare in northern Europe and the US. Previous reports have suggested that there may be ethnic and racial differences in disease presentation and possible clustering of manifestations. We started a dedicated Behcet clinic in 2004 and now report on the disease characteristics of the first 347 patients, we believe representing thus far the largest cohort in the US Methods: All patients seen at the center have complete a MDHAQ, and a questionnaire about past medical history, medication use, Behcet specific history, ethnic and demographic information. These data are prospectively collected and updated each visit. About 2/3 of patients live within driving distance of NYC while patients from over 30 states have been seen. Patients were analyzed as the whole cohort and then also separated into to 2 groups: Group A= with ethnic background in northern Europe and North America and/or self declared Caucasians without background around the Mediterranean and/or the Far East; Group B= Patients with an ethnic background in the Mediterranean, Middle East, North Africa, and Far East. These groups were compared for disease manifestations, demographic information and medication use. Results: 347 patients (76% female, mean (SD) disease duration 3.8 (5.4) years, mean (SD) age 53 (13)) of whom 88% fulfilled the International Behcet classification criteria, were analyzed. For the whole cohort most common symptoms were oral ulcers (94%), genital ulcers (76.2%), skin involvement (70.2%), arthritis (54.7%), GI disease (37.9%) and eye disease (27.9%). 15.2% had CNS, 9.7% had vascular/DVT involvement. Less than 10% were positive for pathergy test and 11% had a positive HLA B51. None of the patients were blind. Group A had statistically more significant GI disease (47.5% vs. 27.4%, p<0.001). There were also more females in Group A, compared to Group B (Group A: 85%, Group B:69%, p<0.001). Most commonly used medication was low dose prednisone (69.6%), in most patients as needed for flares, followed by colchicine (50.9%), TNF inhibitors (23.3%) and azathioprine (22.5%). 17.6% were on methotrexate, the only medication with significantly different frequency of use among the two groups (Group A=26.8%, Group B=8.6%, p<0.001). Conclusion: In this cohort of 347 BS patients, largest cohort in the US to the best of our knowledge, some clinical differences were noted between patients with different ethnic backgrounds. There were significantly more female patients in the non-ethnic groups and GI disease was significantly more among these patients also. Eye disease prevalence for both groups was less than reported from other centers and may be less severe as none of the patients were blind. These finding may have implications regarding the pathogenesis and the effect of nature vs nurture on the presentation of BS in different geographic areas

Purpose: The Bath ankylosing spondylitis disease activity index (BASDAI) and Bath AS Function Index (BASFI) were developed as outcome measures to assess and monitor patients with ankylosing spondylitis (AS). Although widely used in clinical trials and other clinical research, these questionnaires are not commonly used in routine clinical care. It is complex to distribute multiple questionnaires to different patients in a reception area. A single questionnaire for all patients with rheumatic diseases may present advantages to introduce quantitative measurement into routine care. A multidimensional health assessment questionnaire (MDHAQ) has been developed to be used as part of the infrastructure of routine care and has been used in the clinics of the senior author for close to 10 years in every patient with any diagnosis. Routine assessment of patient index data 3 (RAPID3) is a composite index based on 3 MDHAQ components, patient function, pain and patient global assessment, each scored 0-10 for a total of 0-30. The MDHAQ has been shown to be useful in RA, OA, fibromyalgia and Behcet's syndrome. Method: Consecutive AS patients seen at Haydarpasa Numune Training and Research Hospital, Physical Medicine and Rehabilitation Outpatient Clinic in Istanbul, Turkey, between May 18 and June15, 2009 were enrolled. All patients completed a BASDAI (score range 0-10), BASFI (score range 0-10) and MDHAQ and had medical records reviewed for additional demographic information, disease characteristics, medication use and selected laboratory test results. Spearman correlations were computed for components of MDHAQ and RAPID3 (score range 0-30) with BASDAI and BASFI. Results: 51 AS patients were assessed (mean (SD) age:30 (10.9) 69% male, disease duration: 5.0 (6.7) years). Mean scores for BASDAI, BASFI and RAPID3 were 4.9 (2.5), 3.6 (2.5) and 12.9 (7.0), respectively. RAPID3 was strongly correlated with BASDAI and BASFI (r:0.77, and 0.72, p<0.001). Individual components of the MDHAQ (pain r:0.72, 0.6) patient's global assessment (r:0.8, 0.65), function (r:0.5, r:0.73), MD global assessment (r:0.7, r:0.76) and fatigue (r:0.62, r: 0.53) (all p<0.01), were also correlated significantly with both BASDAI and BASFI, respectively. Conclusion: RAPID3, on an MDHAQ was strongly correlated with the outcome measures of BASDAI and BASFI in AS patients. Additional measures in the MDHAQ were also correlated. This extends findings that an index of patient measures, RAPID3, may provide a user-friendly index and an effective measure in clinical care of individual patients with AS

Purpose: EULAR/ACR recommendations stress the importance of reporting the sustainability of treatment responses in patients (pts) with RA1. Here we assess the likelihood of maintaining/improving initial improvements in the signs/symptoms of RA and physical function with abatacept over 1 year (yr), in MTX-naive pts with early RA and poor prognostic factors. Methods: In the 12-month (mth) double-blind period of AGREE (Abatacept study to Gauge Remission and joint damage progression in MTX-nave pts with Early Erosive RA)², pts with RA <=2 yrs received abatacept (~10 mg/kg) + MTX or MTX alone. In these post-hoc analyses, shifts in ACR response and Health Assessment Questionnaire-Disability Index (HAQ-DI) status from Mth 3 to 12 were evaluated in pts who completed the

Purpose: Game consoles such as Xbox, PS3 and Wii, in addition to handheld unit PSP, iTouch and iPhone are used by many children. Data regarding wrist and finger pain that may be caused by excessive use of these devices do not exist, especially in young children. We examined the possible association device type, age of children and hours played may have with wrist and finger pain. Method: 7-12 year olds attending Rossman Elemantary School in St Louis, MO, were administered a questionnaire asking about game consoles and hand-held devices used, hours played, and wrist or finger pain as reported on a 10cm VAS. Summary statistics of playing habits, devices played and pain levels were estimated. Multivariable generalized linear models associating consoles played, age and hours played to pain were constructed using standard backward selection techniques, determining the most significant independent predictors for pain. Results: 171 children completed the survey (mean age 9.7 years, 93 were female (54.4%). 84 (49.1%) reported 0-1 hours of play a day, 58 (33.9%) 1-2 hours, 12 (7%) 2-3 hours and 11 (6.4%) over 3 hours. 20 (11.7%) children reported finger pain and 17 (9.9%) reported wrist pain limiting their playing time. The mean (SD) pain level was 0.83 (1.82). Among the consoles Wii was the most commonly used (n=77, 45%), followed by Xbox/PS3 (n=9, 5.3%). 28 (16.4%) children played with none and 57 (33.3%) played both. For handhelds, Gameboy/PSP were played by 103 (60.2%) and iTouch/iPhone by 10 (5.8%). 39 (22.8%) played both and 19 (11.1%) played with neither. In beta regression, increasing age was independently associated with decreased odds of reporting pain (OR=0.65 (95% CI 0.57 - 0.75)); increasing hours played was associated with increased odds of reporting pain (OR=1.52 (95% CI 1.16-2.00)). Playing the Wii only was also independently associated with increased odds of reporting pain (OR=2.39 (95% CI 1.81-3.73)). In logistic regression, age was the only significant predictor of wrist pain (OR=0.68 (95% CI 0.48-0.96).No significant predictor of finger pain was observed. Conclusion: In children aged 7-12, 80% of which played with a console or handheld, younger age was associated with more wrist pain. Wii use was associated with more self-reported pain independent of age and hours played. Seven year olds reported the most pain as compared the other age groups. These findings may have implications for which age children should start playing with gaming consoles and handheld devices and possibly some limits in the hours they play

OBJECTIVE: To compare 4 categories (high, moderate, and low severity, and near-remission) of RAPID3 (Routine Assessment of Patient Index Data 3), an index without formal joint counts, which is scored in < 10 seconds to 4 categories of the Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI) in patients with rheumatoid arthritis (RA). METHODS: All patients complete a Multidimensional Health Assessment Questionnaire (MDHAQ) at each visit. A physician/assessor 28-joint count and erythrocyte sedimentation rate (ESR) were completed in 285 patients with RA in usual care by 3 rheumatologists to score DAS28, CDAI, and RAPID3. RAPID3 includes the 3 MDHAQ patient self-report RA Core Data Set measures for physical function, pain, and patient global estimate. Proposed RAPID3 (range 0-10) severity categories of high (> 4), moderate (2.01-4), low (1.01-2), and near-remission (</= 1) were compared to DAS (0-10) activity categories of high (> 5.1), moderate (3.21-5.1), low (2.61-3.2), and remission (</= 2.6), and CDAI (0-76) categories of > 22, 10.1-22.0, 2.9-10.0, and </= 2.8. Additional RAPID scores, which add to RAPID3 a physician/assessor or patient self-report joint count and/or assessor global estimate, were also analyzed. Statistical significance was analyzed using Spearman correlations, cross-tabulations, and kappa statistics. RESULTS: All RAPID scores were correlated significantly with DAS28 and CDAI (rho > 0.65, p < 0.001). Overall, 78%-84% of patients who met DAS28 or CDAI moderate/high activity criteria met similar RAPID severity criteria, and 68%-77% who met DAS28 or CDAI remission/low activity criteria also met similar RAPID criteria. RAPID3 was as informative as other indices. CONCLUSION: RAPID3 provides a feasible, informative quantitative index for busy clinical settings