Faculty Bibliography

BACKGROUND:The effect of IL-1 blocking therapy on mucocutaneous manifestations of Behçet's disease is incompletely understood. METHODS:Six patients with Behçet's disease and ongoing oral/genital ulcers for ≥1 month were enrolled into an adaptive, two-phase clinical trial and included in the analysis. Study duration was 6 months with extension up to 16 months. All were treated non-blinded with anakinra 100 mg subcutaneous daily with the option to escalate the dose to 200 mg in partial responders after 1 month and 300 mg after 6 months. Patients recorded the number and severity of ulcers in daily diaries. The primary outcome was remission defined as no ulcers on physical exam for two consecutive monthly visits between months 3 and 6. Secondary outcomes included the number and severity of patient-reported ulcers, patient/physician global scores, and standardized disease activity scores. RESULTS:Two of six patients achieved the primary outcome. Five of six patients had improvement in the number and severity of ulcers. Non-statistically significant improvements were seen in secondary outcomes. Over the entire study, patients reported ≥1 oral and ≥1 genital ulcer on 665 (66%) and 139 (14%) days, respectively. On anakinra 200 mg vs 100 mg, patients reported fewer days with oral ulcers (65% vs 74% of days, p = 0.01) and genital ulcers (10% vs 22% of days, p < 0.001) and milder oral ulcer severity (p < 0.001). Increase of anakinra to 300 mg did not result in further improvements. Adverse events were notable for mild infections. CONCLUSION/CONCLUSIONS:Anakinra at an optimal dose of 200 mg daily had an acceptable safety profile and was partially effective in the treatment of resistant oral and genital ulcers in Behçet's disease. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov. NCT01441076 . Registered on 24 September 2011.

Objectives: An unmet need for reliable, validated and widely accepted outcome measures for trials in Behcets syndrome (BS) was identified through: a systematic review; a survey among Behcets experts; and an outcome measures interest group meeting during the 16th International Conference on BS The OMERACT BS Working Group has been working to advance outcome measures in BS with the goal of creating a core set of data-driven measures for use in clinical trials for BS starting with a Delphi. This abstract describes the results for round one of the Delphi. Methods: A list of possible domains and outcomes was prepared using the results of a systematic literature review on outcomes assessed in previous Behcets studies, qualitative patient interviews, and expert opinion. A three round Delphi has begun among physicians from different specialties experienced in BS and among patients with BS. The patient survey was the same as the physician survey with medical terms explained. The web based survey was formatted in both English and Turkish and emailed to 123 physicians and 130 patients. Agreement by more than seventy percent of either physicians or patients resulted in an item accepted. Results: 74 physicians and 35 patients participated in Round 1. The physicians were experts in BS from 21 countries and from within a wide range of specialties, including Rheumatology, Ophthalmology, Internal Medicine, Dermatology, Gastroenterology, and Neurology. Among the participating patients there was good representation of each type of organ involvement please see Table 1 for results. In addition to these domains, more than seventy percent of patients endorsed the assessment of pain, fatigue, sleep, sexual functioning, psychological functioning, and acute phase reactants in all trials of BS. Conclusions: Multiple disease related domains in BS have been identified by physicians and patients as important to address in clinical trials, suggesting that a core set for all trials will be needed and subdomains for subsets of disease will also be useful. Rating and ranking of these domains and subdomains in the next two rounds will enable the development of a core set of domains to be assessed in trials of BS

BACKGROUND: Rheumatoid arthritis (RA) afflicts approximately 1.5 million American adults and is a major cause of disability. As disease severity worsens, individuals with RA may experience functional decline that can impact dietary intake. OBJECTIVE: The objective of this study is to assess the diet quality of individuals with RA using the Healthy Eating Index (HEI)-2010 and examine associations between diet quality and disease activity and functional status. METHODS: This cross-sectional study assessed diet quality and disease activity and functional status in adults with RA. Participants completed seven-day weighed food records, which were scored using the HEI-2010. Participants had a fasting blood draw and completed the Multidimensional Health Assessment Questionnaire to determine disease activity and functional status. RESULTS: The mean age of individuals with RA ( N = 84) was 53 +/- 14 years, and 86.9% were female. The mean HEI-2010 total score was 58.7 +/- 15.9, with 7.1% of participants scoring "good", 58.3% "fair", and 34.5% "poor". Most participants did not adhere to recommended intakes of total fruit, total vegetables, whole grains, fatty acids, refined grains, sodium, and empty calories. An unadjusted multiple linear regression model found duration of morning stiffness and C-reactive protein concentration to be significant variables to inversely predict HEI-2010 total score. CONCLUSIONS: The diet quality of many individuals with RA needs improvement and may be related to functional disability associated with RA. Healthcare providers should encourage individuals with RA to meet dietary guidelines and maintain a healthy diet. Moreover, healthcare providers should be aware of the potential impacts of functional disability on diet quality in individuals with RA.

Introduction: Mucocutaneous lesions can be disabling in Behcet's syndrome patients who experience these lesions frequently and can be an important cause of impaired quality of life. Apremilast may be a safe and effective alternative for the treatment of oral and genital ulcers in Behcet's syndrome. Areas covered: This review covers the current data on the efficacy and safety of apremilast in BS patients with mucocutaneous involvement coming from a Phase 2 placebo controlled trial as well as the patient important outcomes reported in the same trial. Observational data in a small number of Behcet's syndrome patients with different types of involvement, inadequately controlled with other treatment modalities was also reviewed. Expert opinion: Topical measures and colchicine are traditionally tried as the initial treatment modality for mucocutaneous lesions of Behcet's syndrome. However these measures may not be sufficient for optimal control of oral and genital ulcers. Immunosuppressive agents such as azathioprine and TNF inhibitors or interferon-alpha are being used for patients with resistant manifestations. However adverse events may limit the use of these agents. Apremilast is a promising agent for the management of BS patients with mucocutaneous lesions due to its efficacy and favourable safety profile.

PURPOSE OF REVIEW: Behcet's syndrome is more common in certain geographic regions, however, can be seen outside of these areas and need to be included in the differential diagnosis of many patients, as it has overlapping features with many rheumatologic conditions. RECENT FINDINGS: Especially in regions with immigrant populations, there seem to be similarities to originating countries in Behcet's prevalence, but the syndrome is not limited to those from certain backgrounds and can be seen in others also. There is emerging evidence that even though the prevalence of Behcet's may be similar to that of endemic areas, in nonendemic regions the condition may be less severe, suggesting potential environment agents in determining the severity of the disease. In addition, women seem to be overrepresented in nonendemic areas and may explain part of the reason for less severe symptoms, as Behcet's tends to be more severe in men. SUMMARY: The somewhat different presentation of Behcet's syndrome in nonendemic areas needs to be considered when thinking about Behcet's in the differential diagnosis of patients. Research into potentially less severe form of the disease in nonendemic areas may provide new clues to the pathogenesis of this condition.

BACKGROUND: In the United States, there is racial/ethnic disparity in the care of rheumatoid arthritis (RA), yet there are limited data regarding the impact of varied health care systems on treatment outcomes. OBJECTIVE: The aim fo this study was to compare the frequencies of use of disease-modifying antirheumatic drugs and biologic agents in racial minorities with RA in a single-payer and variable-access health systems. METHODS: Rheumatoid arthritis disease status was examined in the Ethnic Minority Rheumatoid Arthritis Consortium (EMRAC) and Veterans Affairs Rheumatoid Arthritis Registry (VARA); frequencies of prednisone and disease-modifying antirheumatic drugs and biologic agent use at enrollment were documented. Comparisons in frequencies of RA therapies between RA cohorts and white and nonwhite racial subsets were evaluated. RESULTS: The combined cohorts provided 2899 subjects for analysis (EMRAC = 943, VARA = 1956). Routine Assessment of Patient Index Data 3 and Disease Activity Score in 28 Joints scores were equivalent (cohort, racial subsets), as was biologic agent use (26% vs. 28%) between whites and nonwhites. Disease-modifying antirheumatic drug use was greater in EMRAC nonwhites compared with their white counterparts, but similar to all VARA patients (33% vs. 22% [P < 0.001], 36%, 39%, respectively). However, biologic agent use was significantly greater in EMRAC versus VARA patients (37% vs. 22%, P < 0.001). In VARA patients, there was no difference in biologic agent use among racial subsets (22% vs. 21%). In EMRAC patients, biologic agent use was greater in whites than in nonwhites (EMRAC white 45% vs. EMRAC nonwhite 33%, P < 0.001; odds ratio, 1.66) and compared with all VARA subjects (EMRAC white 45% vs. all VARA 22%, P < 0.001; odds ratio, 2.91). Younger age, advanced education, longstanding disease, and severe disease were associated with biologic agent use. CONCLUSIONS: When compared with more variable-access systems, a VA system of care that includes a single-payer insurance may afford equality in use of biologic agents among different racial subsets.

Objective/UNASSIGNED:To compare patients with a primary diagnosis of osteoarthritis (OA) versus rheumatoid arthritis (RA) for scores on a patient self-report MDHAQ/RAPID3 (Multidimensional Health Assessment Questionnaire/Routine Assessment of Patient Index Data 3), and for physician global assessment (DOCGL). Methods/UNASSIGNED:All patients with all diagnoses complete an MDHAQ/RAPID3 at all routine rheumatology visits in the waiting area before seeing a rheumatologist at four sites, one in Australia and three in the USA. The two-page MDHAQ includes 0-10 scores for physical function (in 10 activities), pain and patient global assessment [on 0-10 visual analogue scales (VAS)], compiled into a 0-30 RAPID3, as well as fatigue and self-report painful joint count scales. Rheumatologists estimate a 0-10 DOCGL VAS. Demographic, MDHAQ/RAPID3 and DOCGL data from a random visit were compared in patients with RA versus patients with OA using multivariate analysis of variance, adjusted for age, disease duration and formal education level. Results/UNASSIGNED:Median RAPID3 was higher in OA versus RA at all four sites (11.7-16.8 vs 6.2-11.8) (p<0.001 at three sites). Median DOCGL in OA versus RA was 5 vs 4, 4 vs 3.7, 2.2 vs 2.5 and 2 vs 1. Patterns were similar for individual RAPID3 items, fatigue and painful joint scales, and in stratified analyses of patients aged 55-70. Conclusion/UNASSIGNED:Patient MDHAQ/RAPID3 and physician DOCGL indicate similar or higher disease burden in OA versus RA. Routine MDHAQ/RAPID3 allows direct comparisons of the two diseases. The findings suggest possible revision of current clinical and public policy views concerning OA.

Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. RAPID3 (Routine Assessment of Patient [Pt] Index Data 3) is a pooled index of the three RA core data set pt-reported outcomes (PROs): function, pain, and pt global assessment of disease activity. We compared clinical outcomes, radiographic progression, and PROs at Month 24 in pts achieving remission, low, moderate, and high disease activity (REM, LDA, MDA, and HDA) based on RAPID3 at Month 6. Methods: ORAL Start (NCT01039688) was a 2-year, Phase 3 randomized controlled trial in which MTX-naive pts with RA received tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, or MTX titrated to 20 mg/week over 8 weeks. RAPID3 scores were calculated at Months 6 and 24 for pts with radiographs at both time points. To calculate RAPID3 scores, each of the 3 individual measures (PtGA visual analog scale [VAS], pain [VAS] and HAQ-DI were scored from 0- 10 for a total of 30, and divided by 3 to give an adjusted 0-10 score. Outcomes assessed at Month 24 included REM (defined as <1), LDA (>1-<2), MDA (>2-<4), and HDA (>4) rates based on RAPID3; change from baseline (CFB) in RAPID3, CDAI, and modified Total Sharp Score (mTSS); and proportion of pts with no radiographic progression based on CFB in mTSS <0 and HAQ-DI <0.5 (defined as normative). Results: Pts with RAPID3 HDA at Month 6 had higher baseline RAPID3 scores than those achieving REM/LDA(Table). At Month 6, 24.6%, 32.5%, and 14.1% of pts receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, and MTX achieved REM, respectively; 19.3%, 20.9%, and 17.9% LDA; 33.2%, 26.2%, and 36.5% MDA; and 22.8%, 20.4%, and 31.4% HDA. A higher proportion of patients were in RAPID3 REM and LDA with tofacitinib vs MTX. Regardless of treatment group, the majority of pts who achieved a specific response at Month 6 maintained or improved their responses at Month 24. CFB in RAPID3 and CDAI at Month 24 was greatest for pts who were in RAPID3 REM/LDA at Month 6. In each treatment group, patients in REM/LDA at Month 6 were more likely to achieve mTSS <0 at Month 24 than those with RAPID3 HDA at Month 6. Overall, regardless of RAPID3 category, a higher proportion of pts receiving tofacitinib than MTX had mTSS <0. Furthermore, CFB in mTSS at Month 24 with tofacitinib was generally similar across RAPID3 categories; with MTX, it was higher for patients with RAPID3 MDA and HDA. The proportion of pts with normative HAQ-DI scores at Month 24 was highest for pts achieving RAPID3 REM at Month 6, and lowest for those in RAPID3 HDA at Month 6, for each treatment group. Conclusion: The majority of pts who attained a RAPID3 response at 6 months maintained that response at 24 months. More pts achieving RAPID3 REM or LDA at Month 6 were radiographic non-progressors or had normative HAQ-DI scores at Month 24, compared with those in RAPID3 MDA or HDA.(Table Presented)

Background/Purpose: This study examined treatment patterns in a rheumatology patient (pt) population initially prescribed innovator infliximab (IFX) that either switched to biosimilar infliximab (CT-P13) or continued on IFX following availability of CT-P13 in the Turkish healthcare system. Methods: Adult pts with >1 diagnosis code (ICD-10-CM M05.X; M06.X) for rheumatoid arthritis (RA) and a prescription for IFX were identified in a national Turkish health care database during the study period (01DEC2010-01DEC2015). Eligible pts were those who continued on IFX (Continuers cohort; CC) or switched from IFX to CT-P13 (Switchers cohort; SC) during the identification period; had continuous medical/pharmacy benefit enrollment >12 months before and >6 months after the index date (date of switch for SC and a random IFX prescription date for CC); had a prescription claim for IFX within 16 weeks of the index date during the baseline period. Demographics, concomitant disease, medications, and treatment patterns (dose, refill interval, discontinuation, and switch) were summarized. A confirmed discontinuation was defined as a switch to another biologic medication or the absence of an index biologic claim for >120 days without censoring. Patient weight was unavailable in the dataset. Results: Key results are shown in the Table and Figure. A total of 3018 pts met study criteria. The majority (95%; n=2870; CC) continued on IFX and had a mean age of 44 years; 46% were female and mean follow up of 12 months. A total of 148 pts (5%) switched to CT-P13 ( SC) and had mean age of 44 years; 51% female and mean follow up of 9 months. Approximately 40% of pts in each cohort had a concomitant diagnosis for ankylosing spondylitis (AS; Table). Other concomitant diseases and medications appeared balanced between cohorts. In the CC, pts had an average of 4.7 infusions at a mean dose of 4.4 vials approximately every 10 weeks. In the SC, pts had an average of 2.6 infusions at a mean dose of 3.6 vials approximately every 10 weeks. Therapy discontinuation occurred in 38% in the CC; average time to any discontinuation or censoring of IFX was 256 days (Table). In the SC, CT-P13 discontinuation was observed in 82%; average time to any discontinuation or censoring of CT-P13 was 124 days; 74% of SC switched to another biologic with 94% of these returning to IFX. Conclusion: This study shows switching from IFX to CT-P13 was infrequent. However, in those switching to CTP13, a high percentage (82%) of CT-P13 discontinuation was observed and the majority returned to IFX. Further studies are needed to understand the reasons for these observations. (Table Presented)