Faculty Bibliography

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We evaluated the relationship between disease activity, according to Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background MTX. RAPID3 scores were calculated at baseline, month (M)6, and M24, and defined as remission (≤ 3), low (LDA; > 3-≤ 6), moderate (MDA; > 6-≤ 12), or high disease activity (HDA; > 12). Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and radiographic non-progression (modified Total Sharp Scores ≤ 0) at M24 were evaluated by M6 RAPID3 response. Among patients receiving tofacitinib 5 or 10 mg BID, respectively, 42.2 and 51.5% (ORAL Start) and 29.8 and 39.0% (ORAL Scan) achieved RAPID3 remission/LDA at M6. Most patients maintained/improved RAPID3 responses at M24. A higher proportion of patients in RAPID3 remission/LDA versus MDA/HDA at M6 achieved CDAI remission, reported normative HAQ-DI scores (< 0.5), and achieved both normative HAQ-DI scores and radiographic non-progression at M24. Patients achieving RAPID3 remission/LDA after 6-month treatment with tofacitinib 5 or 10 mg BID have improved long-term outcomes versus patients with MDA/HDA. These findings support the use of RAPID3 to monitor longer-term disease activity in conjunction with physician-assessed measures.

Background: Behcet's syndrome (BS) is an auto-inflammatory vasculitis, most common in countries along the ancient Silk Road. Classification of BS most often is done with the International Study Group criteria (ISG criteria)1. ISG criteria positivity for BS is reached when a patient has recurrent oral ulceration and any two of the following symptoms: recurrent genital ulceration, uveitis, skin lesions and pathergy positivity. However, many other manifestations are reported1. Differences in clinical presentation can complicate classification of the diagnosis, especially in areas where the disease is low in prevalence. Thus, some patients are classified as "probable BS". In some of these cases patients developed additional symptoms over time and met the ISG criteria in a later stage. Objectives: To describe characteristics of patients presenting with a probable diagnosis of BS in Amsterdam and New York and to study if patients who eventually met the ISG criteria differ from those who did not. Methods: We included consecutive patients classified as possible BS to our outpatient clinics in New York and Amsterdam. Patients fulfilling ISG criteria at enrollment were excluded, as well as patients in whom an alternative diagnosis was made at enrollment. Baseline data were evaluated retrospectively and patients were divided into two groups: those developing ISG positive (ISG +or "true") BS during follow up and those who did not meet ISG criteria after follow-up (ISG-). Turkey, Asia, Middle and Far Eastern countries, Arabic countries and Northern Africa were considered endemic areas; Italian, Greek, Hispanic, Portugese, African- American and Caucasian patients were considered not from endemic areas. Statistical analysis was performed using SPSS, with Chi-square tests or Fisher's exact tests for categorical data and independent sample t-tests for numerical data. Results: 189 patients were included, of whom 20 were from Amsterdam. During follow up, 71 patients (37.6%) could be classified as "true" Behcet's syndrome after a mean period of 9.4 years (+/-8.3 years) after onset 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 for both groups. Labial ulcers and skin manifestations at enrollment were more frequently reported. Genital ulcers as a group was not significantly associated with developing "true" Behcets, nor were specific skin manifestations such as erythema nodosum. We also considered HLA-B*51, pathergy, erythrocyte sedimentation rate and C-reactive protein, but due to a large amount of missing data, we were unable to draw any significant conclusions for these variables. Figure 1 Baseline data from all patients who were classified as probable Behcet's syndrome at enrollment Conclusions: About a third of patients classified as probable Behcet's syndrome at enrollment develop new manifestations over time. Thus, they can be reclassified as ISG positive ("true") BS. Based on our data, presence of skin manifestations and labial ulcers at enrollment was significantly higher in the group eventually developing a ISG criteria positive BS

The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest multiple pathological pathways are involved in Behçet syndrome. These features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 to be the important genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bone fide disease, especially in non-endemic regions, suggests other factors must also be operative in Behçet syndrome. This consideration is also true for the newly proposed 'MHC-I-opathy' concept. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease (such as Budd-Chiari syndrome and pulmonary artery involvement), eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve.

This corrects the article DOI: 10.1038/nrrheum.2017.208.

PURPOSE OF REVIEW: Biomarkers are considered to be helpful in diagnosing, monitoring, predicting treatment response, and prognosis in clinical practice and as outcomes in clinical trials. In this article, we review the recent literature on new biomarkers and the expanding use of older ones in vasculitic conditions. RECENT FINDINGS: In antineutrophil cytoplasmic antibody-associated vasculitis patients antineutrophil cytoplasmic antibody type may be useful as a predictor of relapse and response to rituximab. Moreover, serial measurements of proteinase-3 titer may help to predict relapse. Urinary soluble CD163 levels are promising for identifying active renal vasculitis. Imaging modalities such as positron emission tomography, computerized angiography tomography, and temporal artery ultrasound maintain their role in diagnosis and disease assessment in large vessel vasculitis. Fecal calprotectin is a useful marker of active gastrointestinal involvement in Behcet's syndrome. SUMMARY: The publications reviewed here potentially may help to move the field of biomarkers in vasculitis management. However, more work toward understanding the underlying pathophysiology and effects of an intervention on the disease process are needed before true biomarkers can be realized. Further studies with appropriate control groups, using good definitions for disease states such as activity and remission are needed to guide our use of these markers correctly in the management of our patients.

Purpose/UNASSIGNED:(infliximab [IFX]) and either continued IFX or switched to CT-P13. Materials and methods/UNASSIGNED:Adult RA patients with ≥1 IFX claim were identified from the Turkish Ministry of Health database. Eligible patients initiated and continued IFX treatment (continuers cohort [CC]) or initiated IFX and switched to CT-P13 (switchers cohort [SC]) during the study period. The initial IFX claim date was defined as the index date. The switch/reference date was defined as the CT-P13 switch date for the SC or a random IFX date during the period of CT-P13 availability for the CC. Cohorts were matched by age, sex, and number of IFX prescriptions during baseline. Patient demographics, discontinuation, and switching were summarized. The baseline period was defined as the period from the index date to the switch/reference date. The follow-up period ranged from the switch/reference date to the end of data availability. Results/UNASSIGNED:<0.001). Conclusion/UNASSIGNED:Treatment patterns differed between patients prescribed IFX and CT-P13. In Turkey, RA patients maintained on IFX had greater treatment persistence (ie, fewer and later discontinuations) than those who initiated IFX and switched to CT-P13.

Purpose/UNASSIGNED:Biosimilar IFX (CT-P13) received marketing approval in Turkey for treatment of rheumatologic diseases, including ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Population data on real-world treatment patterns of CT-P13 following marketing approval in European countries are largely unreported. This study examined the prescribing and medication utilization patterns of innovator infliximab (IFX) and CT-P13 in Turkey for patients with RA or IBD naïve to either IFX. Materials and methods/UNASSIGNED:Adult patients with ≥1 diagnosis claim for RA or IBD and ≥1 claim for IFX or CT-P13 were identified in the Turkish Ministry of Health database during the following identification periods: 1 Oct 2014-30 May 2015 (RA) and 1 Oct 2014-31 Dec 2015 (IBD). Continuous medical and pharmacy coverage for ≥12 months before and after the date of the first dose (index) IFX or CT-P13 was also required. Separate analyses were done for each population. Results/UNASSIGNED:Seven hundred and seventy nine adult RA and 581 IBD patients met the selection criteria. The majority of RA (74%; n=575) and IBD patients (87%; n=504) were initiated on IFX. The average study observation period was 16 months for the RA and 12 months for the IBD population. Over the observation periods, discontinuation among RA patients occurred in 42% of IFX and 63% of CT-P13 while discontinuation in the IBD cohort occurred in 38% of IFX; and 62% of CT-P13. Conclusion/UNASSIGNED:In this population-based study, more IFX-naïve RA and IBD patients were initially treated with IFX than CT-P13. Discontinuation and switching were observed more often and earlier among patients treated with CT-P13 regardless of disease state. Further studies are needed to understand the reasons for these observed differences.