Faculty Bibliography

Background: The Routine Assessment of Patient Index Data 3 (RAPID3) is an outcome measure of disease activity widely used in the USA as part of routine care1 and is entirely derived from patient self-reported measures (Health Assessment Questionnaire-Disability Index [HAQ-DI] or multidimensional HAQ [MDHAQ], Pain visual analog scale [VAS] and Patient's Assessment of Disease Activity [PtGA] VAS). However, the lack of more objective, traditional physician assessments, such as joint counts, may lead to residual active disease that will be missed.
Objective(s): To examine trajectories for improvement in RAPID3 score over time and PsA manifestations not measured specifically by RAPID3 in subjects achieving RAPID3 near remission (REM) or low disease severity at Week 52.
Method(s): Pooled analyses of the phase III PALACE 1, 2 and 3 studies were performed for subjects assigned to receive APR 30 mg twice daily (BID) at baseline (BL). Subjects with available scores on RAPID3 components (HAQ-DI, Pain VAS and PtGA VAS) at Week 52 were included and grouped according to RAPID3 categories at Week 52 (near REM: <=3; low: >3 to <=6; moderate: >6 to <=12; and high: >12 to 30). Mean RAPID3 scores were assessed from BL through Week 52. Other measures of PsA disease activity were reported longitudinally by RAPID3 category at Week 52.
Result(s): The analysis included 376 APR subjects, with 42 with near REM and 42 with low severity at Week 52. Overall, mean RAPID3 trajectories improved overtime with greater mean improvements observed for those achieving RAPID3 near REM and low disease severity by Week 52. At a mean level, subjects in moderate RAPID3 at baseline were associated with achievement of RAPID3 near REM or low disease severity by Week 52 with APR (Figure). Many subjects who achieved RAPID3 near REM or low disease severity at Week 52 showed improvements in articular and extra-articular disease activity, although not all manifestations were controlled at Week 52 (Table); mean TJC was higher than expected in subjects achieving RAPID3 targets at Week 52 and there was no association between low mean RAPID3 and mean Psoriasis Area and Severity Index (PASI) scores.
Conclusion(s): At a mean level, subjects in moderate RAPID3 at baseline were associated with achievement of RAPID3 near REM or low disease severity targets with APR by Week 52. Achievement of RAPID3 targets was associated with improvement, but not necessarily control, of all articular and extra-articular manifestations. Complementing the RAPID3 measure with joint and skin assessments may help to evaluate achievement of treatment goals in clinical practice

Objectives/UNASSIGNED:Rheumatoid arthritis (RA) is an autoimmune disease accompanied by pain, joint stiffness, and swelling, impacting quality of life. RA is also an articular disorder affecting multiple organ systems. Oxidative stress and antioxidants may play a role in the disease process. The oxidative balance score (OBS) is a composite estimate of exogenous dietary, lifestyle, and medication factors associated with antioxidant and pro-oxidant properties. This study examined the relationship between OBS and disease activity in RA. Methods/UNASSIGNED:-defined pro-oxidant (polyunsaturated fatty acid and iron) and antioxidant (selenium, vitamin C, vitamin E, α-carotene, β-carotene, lutein + zeaxanthin, lycopene, cryptoxanthine; use of aspirin and non-steroidal anti-inflammatory drugs, and alcohol) exposure factors. A higher OBS scored indicated more antioxidant and less pro-oxidant exposure. Partial correlations examined the relationship between OBS and disease activity, while controlling for age, using IBM SPSS Statistics. Results/UNASSIGNED: = 0.103); as OBS increased, physical function, pain, and disease activity improved. No statistically significant relationships were seen between OBS and the other measures of disease activity. Conclusions/UNASSIGNED:In this study, a higher OBS score was associated with lower disease activity. More research is needed to understand the relationship of these lifestyle exposures to RA. Funding Sources/UNASSIGNED:NYU Steinhardt Research Challenge Grant.

OBJECTIVE:Matching-adjusted indirect comparison was used to assess the comparative effectiveness of secukinumab 150 mg and adalimumab 40 mg in biologic-naïve patients with ankylosing spondylitis (AS) for up to 1 year. METHODS:Pooled individual patient data from the secukinumab arms of MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375) trials (n=197) were matched against the AT-LAS (NCT00085644) adalimumab population (n=208). Logistic regression analysis was used to determined weights to match for age, sex, Bath AS Functional Index, C-reactive protein levels, and previous tumor necrosis factor inhibitor therapy. Recalculated Assessment of SpondyloArthritis International Society (ASAS) 20 and 40 responses at weeks 8, 12, 16, 24, and 52 from MEASURE 1/2 (effective sample size=120) were compared with those of ATLAS. Anchored (placebo-adjusted) comparisons were possible until week 12, and unanchored (non-placebo-adjusted) comparisons were necessary thereafter. RESULTS:For placebo-anchored ASAS 20 and 40 comparisons up to week 12, there were no differences between secukinumab and adalimumab. For unanchored comparisons at week 16, ASAS 20 was higher for secukinumab [odds ratio 1.60 (95% confidence interval, 1.01-2.54); p=0.047]; at week 24, ASAS 20 and 40 were higher for secukinumab [1.76 (1.11-2.79); p=0.017 and 1.79 (1.14-2.82); p=0.012, respectively]; and at week 52, ASAS 40 was higher for secukinumab [1.54 (1.06-2.23); p=0.023] than for adalimumab. CONCLUSION/CONCLUSIONS:There were no differences observed in placebo-adjusted ASAS 20 and 40 responses up to 12 weeks between secukinumab- and adalimumab-treated patients with ankylosing spondylitis. After week 12, secukinumab demonstrated signs of greater improvement in non-placebo-adjusted ASAS 20 and 40 responses than adalimumab.

Background/Purpose: Behcet's syndrome (BS) is formally diagnosed using the International Study Group (ISG) criteria, where recurrent oral ulceration and any two other symptoms (recurrent genital ulceration, uveitis, skin lesions and pathergy positivity) are required. The allowance of various symptomology in the ISG criteria has led to the reporting of varied manifestations, and differences in clinical presentation can complicate BS diagnosis, especially in areas where the disease prevalence is low. The purpose of this study was to explore clinical BS symptoms present at initial patient visit that are predictive of ISG criteria diagnosis at follow-up.
Method(s): Data from consecutive patients monitored in outpatient clinics in New York and Amsterdam were abstracted. Patients were included if diagnosis at initial visit was "suspected" or "probable BS"; patients given a formal diagnosis by ISG criteria at initial visit or a non-BS diagnosis at initial visit were excluded. Demographic data, including ancestry/ ethnicity, clinical symptoms, duration of symptoms and RAPID3 were abstracted from initial visit, with follow-up ISG status (defined as meeting criteria ISG+ vs not meeting criteria ISG-) abstracted from last visit. Univariable logistic regression was used to screen initial visit clinical features and symptoms with follow-up ISG status. All variables that passed screening at P <=0.10 were included in the final multivariable model2.
Result(s): 189 patients were included: 169 from NY and 20 from Amsterdam. 71 (37.6%) patients were classified as ISG+ with an average of 9.4 years (+/- 8.3 years) of symptoms. Age, gender, ethnicity, duration of symptoms at enrollment, duration of follow up as well as RAPID3 and almost all clinical manifestations at baseline were comparable between ISG+ And ISG- patients. Presence of morning stiffness, family history of BS, genital ulceration, labial ulceration, skin lesions, eye disease and retinitis were each identified in the univariable model as being possibly associated with prevalence of ISG+. The final multivariable model did not include correlated symptoms (i.e. genital and labial ulceration as well as eye disease and retinitis). In the final model, presence of morning stiffness, genital ulcers, skin lesions, and eye disease were associated with increased odds of ISG+, adjusting for age, symptom duration and family history (Figure). Area under the curve was 0.718, indicating acceptable predictive capability of the final model.
Conclusion(s): Based on our data, over a third of patients with suspected or probable Behcet's developed new manifestations over time that led to classification as ISG+ Behcet's. Despite development of these new manifestations, the presence of morning stiffness, genital ulcers, skin lesions, and eye disease at initial visit were independently associated with significantly higher odds in developing ISG+ Behcet's during followup. (Figure Presented)

Background/Purpose: Behcet's syndrome is a chronic, multi-systeminflammatory disorder characterized by recurrent oral ulcers (OU) that can bedisabling and negatively affect quality of life. Apremilast (APR), an oralphosphodiesterase 4 inhibitor that modulates inflammatory pathways, has demonstratedefficacy in the treatment of OU of Behcet's syndrome in a phase III, multicenter, randomized, double-blind, placebo (PBO)-controlled study (RELIEF).
Method(s): In this phase III, multicenter study, adult patients with active Behcet's syndrome (with >=3 OU at randomizationor >=2 OU at screening + randomization, without active major organinvolvement) were randomized (1:1) to receive APR 30 mg BID or PBO BID for 12weeks followed by a 52-week active-treatment phase. The primary endpoint was area under the curvefor total number of OU over 12 weeks (OU AUCWk0-12). AUC reflectsthe change in the number of OU over time, accounting for the clinicalcharacteristic that OU repeatedly remit and recur. In a planned analysis, OUAUCWk0-12 was examined among subgroups of patients defined by BLdemographics and disease characteristics.
Result(s): A total of 207 patients were randomized and received >=1 dose of study medication (APR:n=104; PBO: n=103). At BL, mean numbers of OU were 4.2 for APR and 3.9 for PBO. At Week 12, least-squares mean OU AUCWk0-12 (LSmean +/-SE) was significantly lower in patients receiving APR vs. PBO (129.5 +/- 15.9 vs. 222.1 +/-15.9; P<0.0001). A treatment effect in favor of the APR treatment group vs. PBO was observed for AUCWk0-12 for OU counts in each of the prespecified subgroups examined. A favorable treatment effect was observed for each demographic subgroup, BL disease characteristic(including duration of disease and BL OU count), geographic region, and prior use of colchicine and corticosteroids (Figure). The incidence of adverse events (AEs) was comparable between APR and PBO (78.8% and 71.8%, respectively). The most common AEs were diarrhea, nausea, headache, and upper respiratory tract infection; most AEs were mild or moderate in severity.
Conclusion(s): Subgroup analyses of the AUC for the number of OU from BL through Week 12 demonstrated the consistent efficacy of apremilast in all of the subgroups analyzed. The safety profile was consistent with the known safety profile of APR. (Figure Presented)

Background/Purpose: There is an unmet need for reliable, validated, and widely-accepted outcome measures for clinical trials in Behcet's syndrome (BS). The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Behcet's Syndrome Working Group has worked to advance the creation of a data-driven Core Domain Set for use in all clinical trials.
Method(s): The Core Domain Set was developed through a comprehensive, iterative, multi-stage, multi-year project that followed the methodologically rigorous processes and standards set forth by OMERACT: i) a systematic review; ii) a survey among experts in BS; iii) an outcome measures interest group meeting during the International Conference on Behcet's Disease; iv) qualitative patient interviews; v) a three-round modified Delphi exercise involving both patients with BS and a multidisciplinary set of physicians expert in BS, focused on obtaining consensus on the domains of illness necessary in the study of BS; and vi) utilization of the data, insight, and feedback generated by the outlined processes to develop a final Core Domain Set. The final Core Set was presented and put up for a vote of endorsement at the 2018 OMERACT meeting.
Result(s): All steps in the processes outlined were completed. The systematic review clearly demonstrated the substantial variability in the domains studied in clinical trials of BS and a lack availability of validated outcome measures in BS. The survey of physicians, the in-person meeting of experts, and the qualitative research with patients all helped generate an extensive list of candidate domains and sub-domains to consider for use in clinical trials. It also become clear that there was a need and strong interest in delineating domains across the several major organ systems involved in this disease and in recognizing that clinical trials in BS often focus on specific manifestations and not the disease in its entirety. The Delphi involved 74 physicians expert in BS from 21 countries and from a wide range of specialties, and 64 patients from 10 countries. The Delphi utilized both ratings and rankings to prioritize the 56 domains and sub-domains originally under consideration. The final proposed Core Set included 5 sub-domains mandatory for study in all trials in BS, with additional sub-domains mandatory for study of specific organ-systems when that system is the focus of a trial: mucocutaneous (2 additional subdomains), ocular (4), central nervous system (3), musculoskeletal (2), vascular (4), and gastrointestinal (2). The final Core Set was strongly endorsed at the 2018 OMERACT meeting.
Conclusion(s): Multiple disease-related domains in BS have been identified by physicians and patients as important to address in clinical trials, leading to the development and endorsement of a final Core Set of Domains for use in clinical trials in BS. The Core Set provides the foundation through which the international research community, including clinical investigators, patients, the biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective agents