Faculty Bibliography

Background: Behcet's Syndrome Activity Scale (BSAS), a patient reported outcome measure for Behcet's syndrome, has been validated for routine clincial care and have been shown to differentiate active treatment from placebo in clinical trials. Currently, there are no identified thresholds for disease activity levels for BSAS. Objectives: To determine resmission, low, moderate and high disease activity level threshold scores for BSAS. Methods: Behcet's patients seen at the NYU Behcet's Center had their demographic, clinical features and outcomes data abstracted. Confirmed Behcet's diagnosis was determined if ISG criteria were met at any time during the course of observation. Concordance correlation was estimated between the BSAS and the RAPID3; both outcomes were scaled to [0-100]. Proposed BSAS severity categories are as: Near-Remission = [0-10), Low = [10-30), Moderate=[30-60), and High = [60-100]. Weighted Kappa statistics were estimated between BSAS and RAPID3 severity categories. RAPID3 categories were based upon published1 as well as matching the proposed BSAS severity categories. Results: First observation data on 832 subjects were abstracted for this analysis. 504 (63%) met ISG criteria for Behcet's, 616 (74%) were female with an average (Table Presented ) age of 35 years (+/-13.8). Concordance between BSAS and RAPID3 was moderate (CCC =0.518). BSAS severity categories classified 7% Near-Remission, 24% Low, 48% Moderate, and 21% of the study population as High disease severity (Table). Published RAPID3 categories classified 44% of subjects as High, while matching RAPID3 categories only classified 20%. Agreement between categories was moderate for both RAPID3 classifications. Conclusions: BSAS, a patient reported outcome measure for Behcet's syndrome, correlates well with other composite indices of disease activity. Proposed cut off points for near-remission, low, moderate and high activity for BSAS may be used in clinical care for a "treat-to-target" approach to Behcet's treatment

Background: Due to a small number of clinical studies, treatment of Behcet's syndrome (BS) mainly depends on the type and severity of symptoms and may vary substantially. In 2008, EULAR recommendations were published, aiming for an evidence-based approach for the management of BS [1]. Objectives: To assess guideline adherence in treatment of BS in two different geographic areas. Methods: We extracted guideline statements from the 2008 EULAR recommendations [1]. Adherence to these statements in both New York (USA) and Amsterdam (The Netherlands) was evaluated retrospectively by reviewing records from patients fulfilling the ISG criteria. We analyzed data per statement and event, and divided the data according to the year in which an event occurred. We compared events prior to 2009 to those in 2009 or later (after publication of the EULAR recommendations). Results: 474 patients were evaluated, 24 of whom were from Amsterdam (Table 1). Adherence in posterior uveitis was relatively low in clinical practice. However, secondary analysis of the patients in the second time frame showed that 66% of cases with partial- and 77% with non-adherence were on cyclosporine or a biologic DMARD. Colchicine in treatment of arthritis was hardly ever used as monotherapy (3 cases <2009, 9 cases >2009). Other drugs used included prednisone (n=197), Plaquenil (n=63), methotrexate (n=67), azathioprine (n=133) and anti-TNF agents (n=124). Conclusions: Adherence to the guidelines varies substantially across type of events. Adherence in treatment of posterior uveitis was low and a variety of other drugs were used in its treatment, which are also considered DMARDs for this condition. The extensive use of anti-TNF agents might indicate a shift towards more aggressive treatment and acceptance of TNF inhibitors for the treatment of other rheumatic and inflammatory eye conditions in the countries studied. In patients with neuro-Behcet, adherence to the recommendation is quite good in clinical practice. In the majority of patients with arthritis, colchicine is either used in combination with other (biological) DMARDs or not at all. This might indicate that colchicine alone is not sufficient as treatment of arthritis in BS or that arthritis is often combined with other manifestations implying a need for more combination treatment. Our results suggest that a revision of the current guidelines may be due, given widespread use of other immunosuppressive medications and newly available studies of these medications. (Table Presented)

Background: Methotrexate (MTX) is the most commonly used conventional synthetic DMARD (csDMARD) for the treatment of rheumatoid arthritis (RA). In the phase 3 MOBILITY study (NCT01061736),1 of sarilumab in inadequate responders to MTX, MTX was continued at the dose prescribed at screening, which was assumed to be the maximally tolerated dose. This sub-analysis evaluates whether the different doses of MTX, in association with sarilumab, had an effect on efficacy or safety outcomes in MOBILITY. Objectives: To explore the relationship of MTX dose on the efficacy or safety of sarilumab in the treatment of active RA in MTX-IR patients. Methods: The MOBILITY study design and methods have been reported.2 Patients were required to be on a stable dose of MTX of 10-25 mg/wk for at least 6 weeks, except for Asian-Pacific region patients (6-25 mg/wk) prior to enrolment and to maintain this dose throughout the trial. A sufficient number of subjects with doses of 7.5-25 mg/wk were included: 11 (0.92%) patients were excluded from the analysis due to small numbers receiving doses of <7.5 and >25mg/wk. The relationship between efficacy and safety outcomes for sarilumab and MTX was assessed by appropriate regression models (logistic or generalized linear) in this post hoc analysis. Results: 1186 patients were included. For each dose group in each treatment arm we computed proportions of ACR20 responders at Wk 24 and 52; no apparent difference in achieving an ACR20 response was observed with increasing MTX dose in any treatment group (Figure). A logistic regression assessment confirms this observation: for sarilumab 150 mg and 200 mg. Based on mean change from baseline in HAQ-DI at Wk 24, no apparent relationship with MTX dose was observed. A linear regression model assessment provides confirmation of the results. There was no statistical difference in mean HAQ-DI change from baseline based on MTX dose in the Pbo, sarilumab 150 mg or sarilumab 200 mg groups. Similar findings were observed for changes from baseline for DAS28-CRP, FACIT-Fatigue, and mTSS (change and progression). There was no association of the incidence of treatment-emergent adverse events (AE), serious AEs and changes in ALT, neutrophil counts and lipids with increasing MTX doses. Conclusions: In this post hoc analysis, within the sarilumab 150 mg or sarilumab 200 mg dose groups, efficacy or safety was similar across concomitant MTX Doses. (Figure Presented)