Faculty Bibliography

One of the major developments in the treatment of rheumatoid arthritis over the last decade and a half has been the realization that early and aggressive treatment leads to better outcomes for most patients. Early use of methotrexate and switching to a combination treatment regimen within the first 3-6 months if there is inadequate response to methotrexate is the currently accepted paradigm for rheumatoid arthritis treatment. To achieve better outcomes it is not enough to just use combination treatments; disease activity also needs to be measured and monitored with a 'treat-to-target' approach, where remission or low disease activity is the target and available medications are used either alone or in combination to get there. 2013 Future Medicine Ltd

Background With the availability of multiple biologic agents, with different modes of action, and no head to head trials, it is of use to examine comparative effectiveness of these agents in real world registries to inform physicians how they might be used for the treatment of rheumatoid arthritis. Objectives To compare time to response and efficacy among biologic agents. Methods Usage of the biologic medications abatacept, adalimumab, etanercept,infliximab and rituximab along with self-reported disease activity and clinic measures were abstracted from ARMD registry at NYU. Time to first response defined as an improvement in RAPID3 of at least 3.6 was calculated; change from biologic medication initiation to first response for self-reported disease activity and clinic measures was estimated. Differences in time to first response between biologic medications were estimated using Cox proportional hazards model. Results 4299 encounteres were reviewed for this analysis. A total of 526 treatment courses were determined. 406 of 526 courses represent the first biologic medication used by an individual; 88 individuals used two biologic medications at different times, while 26 had used three biologics, and 6 had used 4. Abatacept had more patients achieve response (66%) characterized by a reduction in RAPID of 3.6 points or greater than adalimumab (63%), etanercept (61%), infliximab (43%), rituximab (41%) although this difference was not statistically siginficant. Increased age and increased duration of disease were associated with decreased likelihood of achieving a RAPID3 reponse. Time to reponse in the first 6 months after treatment was not significantly different among any of the biologics Conclusions No differences in efficacy and time to response among adalimumab, abatacept, etanercept, infliximab or rituximab in the first 6 months after RA treatment was initiated were noted. With no difference in clinical outcomes, most treatment decisions may be based on ease of use and safety data of respective!

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 Estimates of global status by doctors (DOCGL) and patients (PATGL) are discordant in about 30-40% of patients with rheumatoid arthritis (RA).1,2 This discordance has been analyzed to date only in RA patients. Objectives To analyze levels of discordance between DOCGL and PATGL in all patients with any diagnosis seen in usual clinical care at a rheumatology setting. Methods Each patient seen at an academic rheumatology clinical setting since 2005 completes a self-report MDHAQ (multidimensional health assessment questionnaire) at each visit, with scales for physical function, pain, PATGL, fatigue, anxiety, depression and quality of sleep, and demographic data. DOCGL was completed by 2 rheumatologists. One random visit of patients seen between 2005 and 2011 was analyzed, patients were classified as PATGL=DOCGL (PATGL and DOCGL within 2 of 10 units), PATGL>DOCGL (PATGL >2 units than DOCGL), and DOCGL>PATGL (DOCGL >2 units than PATGL). Univariate odds ratios were computed to identify variables associated with discordance. Significant variables (p<0.05) were included in multivariate models, with selected variables when indicated. Results In a total of 980 patients studied, 509 (52%) had PATGL=DOCGL, 371 (38%) PATGL>DOCGL, and 100 (10%) DOCGL>PATGL. Patients with PATGL>DOCGL were more likely to be female, have less formal education and have higher MDHAQ scores (Table). In multivariate analysis, higher pain and fatigue scores were independent predictors of PATGL>DOCGL. If MDHAQ scores for pain and fatigue were not included in a second model, female gender, lower education and higher scores for depression and sleep problems were independent predictors of PATGL>DOCGL. In patients with DOCGL>PATGL, only lower fatigue was associated in multivariate analysis with lower odds of discordance (OR=0.88, 95% CI 0.79-0.98). Conclusions 38% of patients estimated their statusas worse than their physicians. These patients were more likely to score higher for pain and fatigue, be female and less educated tha!

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!