Faculty Bibliography

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 retrospective healthcare claims analysis examined treatment patterns of innovator infliximab (IFX) and biosimilar infliximab (CT-P13) in a Turkish rheumatologic disease population after CT-P13 availability in July, 2014. Methods: Adult patients (pts) with >1 diagnosis code (ICD-10-CM) for rheumatoid arthritis (RA) were identified in a national Turkish healthcare database during the study period (01DEC2010-01DEC2015). Eligible pts had continuous medical/pharmacy enrollment >12 months before and >6 months after IFX or CT-P13 initiation (index date). Patients were naive to IFX or CT-P13 (i.e. had no IFX or CTP13 within 12 months before the index date). Demographics, concomitant diseases and medications, and treatment patterns, eg., dose, interval, discontinuation, and switch were summarized. Confirmed discontinuation was defined as a switch to another biologic medication or the absence of an index biologic claim for >120 days without censoring. Results: Key results are shown in the Table. A total of 1044 patients initiated either medication. The majority (80%; n=831) initiated IFX. The IFX cohort had a mean age of 42 years; 56% were women and mean follow up was 12 months. The CT-P13 cohort consisted of 213 pts with mean age of 43 years; 58% women; and mean follow up of 9 months. Approximately one-third of pts in each cohort had a concomitant diagnosis of ankylosing spondylitis (AS; TABLE). Other concomitant diseases and medications appeared balanced between cohorts. Pts in the IFX cohort had an average of 5.2 infusions and mean dose of 4.7 vials per infusion approximately every 8 weeks. Pts in the CT-P13 cohort had an average of 3.6 doses and mean dose of 5.8 vials per dispensing approximately 9 weeks apart. A confirmed discontinuation occurred in 55% of the IFX cohort; driven in part by switching. 24% of IFX pts had > 1 biologic switch with 8% initially switching to CT-P13. Time to any discontinuation or censoring of IFX is shown in the Figure and Table. In the CT-P13 cohort, a confirmed discontinuation was observed in 63%; 31% switched to another biologic therapy; and 20% initially switched to IFX. Time to any discontinuation or censoring of CT-P13 is shown in Figure and Table. Conclusion: These findings in a single country indicate that real world utilization patterns may differ between innovator IFX and CT-P13, with predominantly more patients initiating IFX; greater overall CT-P13 discontinuation and a higher proportion of patients switching from CT-P13 to IFX. Further studies are needed to understand the reasons for these observed differences. (Table Presented)

Socioeconomic Status and Not Race Associated with Delay in Diagnosis and Treatment of Rheumatoid Arthritis Background/Purpose: Ethnic disparities in outcomes of RA patients have been attributed to delayed presentation to specialty care and access to DMARDs, greater disease burden, and less years of education. Recent literature supports a role for socioeconomic status (SES) as a determinant of RA disease status, including clinical disease activity measures, mortality, seropositivity, and treatment delays. The purpose of this analysis was to delineate the association of SES to referral time and start of first DMARD in a diverse cohort of RA patients. Methods: Ethnic Minority RA Consortium (EMRAC) participants with recorded dates of initial RA symptom, diagnosis and first diseasemodifying drug (DMARD) were abstracted for analysis. Socio-demographic (age, gender, race, years of education, tobacco use), and RA disease status (disease duration, erosions, tender and swollen joints, RAPID3) at enrollment was documented. An estimate of SES was derived from the median housing income of the city of each enrollment site. Median incomes less than two-fold the 2014 poverty line ($47,700) defined lower SES status. Delays of ³ one-year for diagnosis and DMARD initiation were both defined from date of initial RA symptom. Logistic regression was used to model the association between risk factors and a one-year delay of diagnosis and DMARD initiation. Results: 269 EMRAC participants with self-reported race/ethnicity and disease history were evaluated; 202 (75%) were female. The average values for the following parameters were: age 60.4 (+/-15.8) years, disease duration 13.6 (+/-10.8) years, and education 12.5 (+/-3.0) years. A majority (200 [74.4%]) of EMRAC participants were enrolled at sites serving lower than the twice poverty line. Significant differences in participant's age, education years, disease activity and race were observed between SES groups (Table). Based upon the logistic regression model, being below the twice poverty line was significantly associated with the increased odds of ³ one-year diagnosis delay [3-fold increase; odds ratio (OR) = 4.0, 95% CI: (1.6, 10.1), P=0.003)] as well as increased odds of DMARD initiation delay [1.4 fold increase, OR = 2.4, 95% CI: (1.1, 5.06), P=0.027)]. There was no association between either diagnosis or DMARD delay and race. However tender joint counts were associated with increased odds of DMARD delay (per tender joint increase OR 1.1, 95% CI (1.01, 1.14), P = 0.028). Conclusion: In a diverse ethnic cohort, disparity in income as an estimate of SES was a strong predictor of delay in referral to a rheumatologist and start of first DMARD. Policies that improve access to specialty care and RA medications must be paralleled by improvements in overall SES of individuals in order to minimize the impact of disease. (Table Presented)

Background/Purpose: An unmet need for reliable, validated, and widely accepted outcome measures for trials in Behet's syndrome (BS) was identified through: i) a systematic review; ii) a survey among Behet's experts; and iii) an outcome measures interest group meeting during the 16th International Conference on Behet's Disease (1,2). The OMERACT Behet's Syndrome 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. To identify domains, subdomains, and outcomes to be assessed in trials of BS, a Delphi exercise among BS experts and patients with BS has been initiated. This abstract describes the results for round 1 of the Delphi. Methods: A list of possible domains, subdomains, and outcomes was prepared using the results of a systematic literature review on outcomes assessed in previous studies in BS, patient priorities identified through qualitative interviews, and expert opinion. A 3- round Delphi was 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 ³70% of either physicians or patients resulted in an item being 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 (50%), Ophthalmology (12%), Internal Medicine (12%), Dermatology (16%), Gastroenterology (3%), and Neurology (1%). Among the participating patients there was good representation of each type of organ involvement. Table 1 shows the domains to be measured in all trials in BS that received ³70% endorsement by expert physicians and the additional subdomains endorsed for trials for each type of involvement. In addition to all of the domains identified by physicians, ³70% of patients endorsed the assessment of pain, fatigue, sleep, sexual functioning, psychological functioning, and acute phase reactants in all trials of BS. Conclusion: 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 (specific manifestations) will also be useful. Rating and ranking of these domains and subdomains in the next 2 rounds will enable the development of a core set of domains to be assessed in clinical trials of BS.(Table Presented)

BACKGROUND: Exercise is associated with major benefits in patients with rheumatic diseases for both cardiovascular and rheumatic status. However, information about exercise generally is not collected systematically in routine rheumatology care. A multidimensional health assessment questionnaire (MDHAQ), which was designed for busy clinical settings, includes a query about exercise status. We analyzed possible associations between change in MDHAQ exercise scores and other MDHAQ measures in patients with various rheumatic diseases over one year. METHODS: In one rheumatology clinical setting, all patients, regardless of diagnosis, complete an MDHAQ before seeing a rheumatologist. The MDHAQ includes scores for physical function, pain, and patient global estimate, compiled into an index, routine assessment of patient index data (RAPID3), as well as a self-report joint count and a query about exercise. Patients were classified into four groups according to their exercise status at baseline and one year later as: EXER-Yes (regular exercise), EXER-Yes; EXER-No (no regular exercise), EXER-Yes; EXER-Yes, EXER-No; and EXER-No, EXER-No. These groups were compared using the chi square and Kruskal-Wallis tests and analysis of variance (ANOVA). RESULTS: Patients who reported regular exercise at baseline were younger, had higher formal education, and better clinical status than other patients. The EXER-No, EXER-Yes group had greater improvement in other MDHAQ variables than patients in the other three groups. By contrast, the EXER-Yes, EXER-No group was the only group with poorer status one year later. CONCLUSIONS: The MDHAQ exercise query indicates that regular exercise is associated with better clinical status. Patients in the EXER-No, EXER-Yes group reported the best clinical improvement, although it is not known whether exercise preceded or followed the improved clinical status.

Background: Patient-reported assessments have a considerable weight both in disease activity assessment in practice and response criteria in clinical trials of rheumatoid arthritis (RA). Discrepancies and disagreement on global disease activity between patients and physicians may result in disagreement in treatment decisions in routine care and impact assessment of treatment response in clinical trials as well. Objectives: We aimed to illustrate the amount of discrepancy between patient and doctor global assessments (PGA and DGA) in routine care and asses the determinants thereof. Methods: We used data from RA patients registered in the Turkish Rheumatoid Arthritis Registry (TRAV), a prospective registry established in 2010 in order to record clinical data at each visit of all RA patients seen at three academic rheumatology centers in a routine care setting. Currently 1923 RA patients are registered in TRAV. We used the initial visits of these patients to define a global assessment discrepancy (GAD) variable, GAD=PGA-DGA. We calculated the average GAD, overall correlation of PGA with DGA and constructed linear regression models to determine the predictors of PGA, DGA and GAD. Age, gender, physical function (MD-HAQ score), pain score (numeric rating scale; NRS), fatigue score (NRS), patient's joint assessment (PJA), physician reported tender (TJC) and swollen joint counts (SJC), erythrocyte sedimentation rate (ESR) and center of follow-up were included in these models as potential predictors. Results: The mean age (standard deviation) of the registered patients was 52.0 (12.8) and 1561 (81%) were females. The average PGA was 3.59 (2.99) and the average DGA was 2.85 (2.63) Overall correlation of PGA and DGA was low (0.18) and average GAD was 0.70 (95% CI: 0.53-0.87). Confidence intervals around GAD indicated that on average patients rated their current disease activity as significantly worse than that of physicians. In the regression analyses; MD-HAQ, pain scores and center were common predictors of both PGA and DGA. Additional predictors of PGA were age, fatigue scores and PJA whereas additional predictors of DGA were ESR, PJA, TJC and SJC. Predictors of GAD were pain, fatigue, TJC, SJC, ESR and treatment center (see table). Conclusions: We found a weak correlation between patient and doctor global assessments of overall disease activity in RA patients under routine care. Higher pain and fatigue scores and different treatment centers were associated with a PGA higher than DGA whereas increasing TJC, SJC and ESR were associated with a DGA higher than PGA suggesting that patients and physicians prioritized different aspects of RA in their global assessments. Variation of the discrepancy by centers warrants further research with respect to a possible impact in multi-center treatment trials. (Table Presented)

PURPOSE OF REVIEW: Currently, there are no diagnostic criteria for vasculitides. To this end, there is a current European League Against Rheumatism and American College of Rheumatology initiative for formulating separate classification and diagnostic criteria for different forms of vasculitis. The authors of this review previously disagreed to separate classification and diagnostic criteria. They now expand this disagreement in light of both of more recent information and a reassessment of older communications. RECENT FINDINGS: We still can find no clear methodologies proposed to prepare separate diagnostic and classification criteria. Furthermore, the inadequate importance given to probabilities in discussing disease criteria was strikingly apparent. Among 77 articles on diagnostic/classification criteria making, not more than 4% discussed Bayes' theorem or predictive values or confidence intervals. The misconceptions related to the worry about circularity and the proper role of nomenclature in classification and diagnostic criteria continue. SUMMARY: Separate diagnostic and classification criteria are unrealistic. Classification criteria and nomenclature are only tools to a proper diagnosis, essentially not different for patient care or research. A frank discussion of probabilities in diagnosis is essential not only with the patients but also with all the stakeholders.