Faculty Bibliography

Background Behcet's syndrome (BS) is a systemic vasculitis that may different pathogenic mechanisms leading to different manifestations, such as eye, mucocutaneous and GI disease. We started a dedicated Behcet's clinic in 2004 and have treated over 850 patients to date. Objectives To determine the response to therapy depending on type of organ involvement and documentation of improvement with patient reported outcomes. Methods All patients seen at the Center complete MDHAQ, medical history, medication use, Behcet's specific history, ethnic and demographic information forms. In addition a Behcet Syndrome Activity Score (BSAS) is also completed by all Behcet patients. These data are prospectively collected and updated each visit. Patients were divided into eye disease only, GI only, both or none groups and compared for disease activity and medication, specifically azathioprine, use. They could have mucocutaneous disease in addition to above manifestations Results 484 patients (78% female, disease duration 4.8 (7.1) years, age 35.3 (13.8)) were analyzed. 244 patients had no eye or GI disease, 83 had eye, 111 GI and 46 both eye and GI involvement. Both groups of azathioprine treated and untreated patients showed improvement in their disease activity scores but the improvement were more pronounced for GI disease by BSAS. RAPID3 responses were more in the azathioprine treated group with eye and both eye and GI disease. Patients with no eye or GI disease did similarly with or without azathioprine. (Table presented) Conclusions In this cohort of 484 Behcet patients, some treatment response differences were noted between patients with eye or GI involvement vs those who did not have these. Overall, azathioprine, led to better outcomes regardless of organ involvement. It was possible to demonstrate these improvements using patient reported outcomes, RAPID3 and BSAS, as part of routine clinical care

Background Randomized controlled trials (RCT) are designed to answer specific questions using a certain number of patients, determined by sample size calculation. If the calculation is not done properly, more than the needed number of patients may be enrolled, leading to unnecessary exposure for those patients to potentially harmful drugs. In an ideal world, assumptions that go into the calculation of the sample size would be more certain. However in the real world it is not always possible to have ideal calculations and it would be expected that under and over enrolling would be seen in roguishly similar number of RCTs. Objectives To determine the actual numbers of patients needed to be enrolled in RA biologic RCT. Methods A Pubmed search was conducted, for RCT of abatacept, adalimumab, etanercept, infliximab, rituximab and tocilizumab, in rheumatoid arthritis (RA) patients (n=291). Only original initial studies where the primary outcome was efficacy were analyzed (n=42). Using the final results of the primary outcome, back calculation of the actually needed patients for the trials were calculated and compared to the actual enrollment numbers. Results 42 studies were analyzed (infliximab 10, etanercept 7, adalimumab 8, abatacept 7, tocilizumab 5, rituximab 5). Primer efficacy outcome was ACR 20 in 29 studies. ACR 50 in 3 studies, ACR N in 2 studies, DAS-28 in 5 studies, Paulus 20 in 2 studies and reduction of number of swollen/tender joints in 1 study. The mean number of patients enrolled in the treatment arms were 153 and the control arms were 114. After back calculation, the actual needed numbers for the treatment arm was 79 and control arm was 79. According to the recalculated sample size results, there were more patient than required to show differences between groups in 35 studies (83%) and less patients than required in 7 studies. In the 35 studies were more than necessary patients were enrolled had a median of 103 extra patients. Conclusions Over 80% of RCT of biologic agents in the tre!

Background The correlation of components of composite activity scores among different patient populations may provide insights into universal applicability and use of disease activity indices. TRAV (Turkish acronym for "Turkish Rheumatoid Arthritis Registry") was established in 2010 with the aim of collecting data on RA. patients seen in routine care in Turkey, the first consecutive patients database to do so. Objectives To compare the correlation of components of composite indices in different RA cohorts from Turkey and US. Methods Consecutive patients seen at participating centers complete at each visit a MDHAQ which includes scales for physical function, pain, and patient global. Physicians complete global assessment VAS, in addition to tender and swollen joint counts. RAPID3 (routine assessment of patient index data), DAS28 and CDAI are calculated. Demographics, self-reported disease activity measures (Pt global), clinical data and medication usage were abstracted from the last visit of individuals with RA seen at Turkish (TR) sites these were compared with patients seen at a US routine care setting, where data have been collected since 2001 on all patients. Patients seen during the same period were used in this comparison. Agreement analysis of physician and patient-reported clinical outcomes were done. Significant differences in measures were determined using the Kruskal-Wallis test for continuous and ordinal measures and Chi-square test for categorical measures. Results 424 TR and 176 US patients were studied. Correlation between MD and Pt global, MD global and pain, DAS28 and RAPID3, MD swollen and tender joint count and Pt self report RADAI joint count are shown in the Table. All measures had similar correlations between US and TR RA patients except MD global and Pt global assessments where US measures showed more correlation than TR patients and physicians. The correlation between patient tender joint count and physicians tender joint count were stronger than swollen joint counts but !

Background CDAI (clinical disease activity index) and RAPID3 (routine assessment of patient index data 3) cut points defining responses that best match ACR20/50/70 response in rheumatoid arthritis (RA) patients (pts), are unknown. Objectives To evaluate cut points in a study population treated with certolizumab pegol (CZP) plus methotrexate (MTX).1 Methods ACR responders through Week (Wk) 12 from 393 CZP treated pts (400 mg at Wks 0, 2 and 4 then 200 mg every 2 Wks) plus MTX in RAPID 1 (NCT00152386) were categorized by proposed response (R) cut points in CDAI (change from baseline [CFB] >6.7, >10.0, >13.9) and RAPID3 (CFB >1.8, >3.6). ACR20/50/70 responses were compared with proposed categorizations using cross-tabulations, AUC under the ROC curve (AUC-ROC), % correctly classified (%CC) pts and kappa statistics. CART2 (classification and regression trees) modeling identified CDAI and RAPID3 cut points defining responses most closely associated with ACR20/50/70 responses. Results Sensitivities were very high; at Wk 12, 93-100% ACR20/50/70 responders achieved CFB in CDAI (>6.7,>10.0,>13.9). Positive predictive value [PPV] was lower indicating CDAI-R is not as strongly associated with ACR-R as ACR-R is with CDAI-R; lower specificities indicate that ACR nonresponse (NR) does not correspond well to CDAI-NR (particularly for ACR50/70). However, CDAI-NR predicts well ACR-NR (very high negative predictive value [NPV]) (Table). CFB in CDAI>13.9 was most closely associated with ACR20-R (=0.57). Association between proposed CDAI categorizations and ACR50/70 was weak (=0.05-0.29). A similar trend was observed for RAPID3. CART modeling identified CFB in CDAI >13.80/>20.15/>20.15 and CFB in RAPID3 >5.46/>7.28/>5.53 as categorizations most closely associated with ACR20/50/70 responses. Conclusions CDAI and RAPID3 CFB thresholds were identified that defined the closest associations with ACR responses in pts with inadequate response to MTX and high disease activity at baseline (mean DAS28 6.9). Sensitivities/NP!

Background Real world applicability of "treat to target" approaches can only be assessed by routine care registries with different patient population and drug use. This also allows comparing RA treatment across different countries and provides insights previously not recognized. TRAV (Turkish acronym for "Turkish Rheumatoid Arthritis Registry") was established in 2010 with the aim of collecting data on RA patients seen in routine care in Turkey, the first consecutive patients database to do so. Objectives To describe the current treatment paradigm and response to treatment among RA patients in Turkey and compare to a US cohort. Methods Consecutive patients seen at participating centers complete at each visit a MDHAQ which includes scales for physical function, pain, and patient global. Physicians complete global assessment VAS, in addition to tender and swollen joint counts. RAPID3 (routine assessment of patient index data), DAS28 and CDAI are calculated. Demographics, self-reported disease activity measures, clinic data and medication usage were abstracted from the last visit of individuals with RA seen at three Turkish sites. Differences in measures from Turkey (TR) and an academic US site where similar data collection has been part of routine care were compared for status of biologic medication usage at last visit, abstracted from the same calendar treatment period. Significant differences in measures were determined using the Kruskal-Wallis test for continuous and ordinal measures and Chi-square test for categorical measures. Results 899 RA patients in TR and 396 in the US were analyzed. There were significant differences between TR and US patients for years of education (TR=6.9 yr, US=14.5 yr) and disease duration (TR=14 yr, US=7.3 yr). Mean disease activity as measured by RAPID3 were similar between the sites (TR=10.5, US=11.2), with similar percentages of patients in remission, LDAS, moderate and high disease activity (TR=21%, 13%, 25%, 41%, and US=19%, 11%, 24%, 46%, respectively) at la!