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ObjectiveIn 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence.MethodsAn updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation.ResultsThree new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering.ConclusionThese 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

ObjectiveIn 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence.MethodsA needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation.ResultsEleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations.ConclusionThe 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

The aim was to evaluate patient satisfaction with virtual care, and identify factors associated with level of satisfaction. Surveys were mailed to all patients who had a phone visit at The Ottawa Hospital Rheumatology division. Patients' satisfaction with various aspects of the phone visits was assessed on a 5-point scale and analyzed according to demographic variables using chi-square and regression analyses. Of 2423 surveys mailed, we received 742 responses (31%). Eighty-nine percent of patients were satisfied overall with the phone visit. Statistically significant less satisfaction was seen in patients who spoke to a resident compared to their rheumatologist (p 0.001), were not called on time (p 0.001), had difficulty using a telephone (p 0.001), needed assistance of a second person (p 0.01), or had new consultations (versus routine follow-up, p = 0.01), the former 3 factors being significant in a multivariate regression analysis. Rheumatology patients expressed a high level of satisfaction with virtual care; however, areas of improvement were identified. Patients' satisfaction will be important to inform future decisions regarding the sustainability of virtual care. Further research is required to understand the impacts of virtual care on patients' Key Points • Patients in rheumatology practice were satisfied with phone visits and preferred this method to in-person visits during the pandemic. • Speaking directly to the rheumatologist, being phoned on time, and the capability of using the telephone were the major determinants of high patient satisfaction. • Based on the identified factors, further improvement of the quality of and satisfaction with phone visits can be pursued given that virtual care may continue longer, beyond the pandemic.

Objective.Aspects of antineutrophil cytoplasmic antibodies–associated vasculitis (AAV) prioritized by patients with AAV were described using the International Classification of Function, Disability, and Health (ICF).Methods.Items identified during 14 individual interviews were incorporated into an ICF-based questionnaire administered to participants of 2 vasculitis patient symposia: 36 in the United Kingdom and 63 in the United States.Results.Categories identified as at least “moderately relevant” by ≥ 5% of subjects included 44 body functions, 14 body structures, 35 activities and participation, 31 environmental factors, and 38 personal factors.Conclusion.Identified categories differ from those identified by the current Outcome Measures in Rheumatology (OMERACT) core set and those prioritized by vasculitis experts.

Background Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is implicated in elevating the risk for cardiovascular (CV) disease; whether the elevated risk applies to all types of CV diseases or specific types is unclear. This study examined the association of AAV and adverse CV outcomes compared with the non-AAV population. Methods We conducted a population-based, retrospective cohort study of adults (mean age 61 years, 51% female) with a new diagnosis of AAV in Ontario, Canada from 2007 to 2017. Weighted models were used to examine the association of AAV (n = 1520) and CV events in a matched (1:4) control cohort (n = 5834). The main outcomes were major adverse CV events (MACE), defined as myocardial infarction (MI), stroke or CV death, its components, atrial fibrillation (AF) and congestive heart failure (CHF). Results Over a mean follow-up of 3.8 years, AAV (compared with non-AAV) was associated with a higher risk of stroke: cumulative incidence 7.0% versus 5.2%, sub-distribution hazard ratio (sHR) 1.49 [(95% confidence interval (95% CI) 1.10–2.02]; AF: cumulative incidence 16.4% versus 11.5%, sHR 1.51, 95% CI 1.30–1.75; and CHF: cumulative incidence 20.8% versus 13.3%, sHR 1.41, 95% CI 1.22–1.62; but not for MACE, MI or CV death. The risks for all CV events, except CV death, were significantly elevated in the early period after AAV diagnosis, in particular AF (365-day sHR 2.06, 95% CI 1.71–2.48; 90-day sHR 3.33, 95% CI 2.66–4.18) and CHF (365-day sHR 1.75, 95% CI 1.48–2.07; 90-day sHR 2.65, 95% CI 2.15–3.26). Conclusion AAV is associated with a high risk of certain types of CV events, particularly in the early period following diagnosis.

OBJECTIVE. Only a few small case series, case reports, and one small clinical trial suggested some benefit of leflunomide (LEF) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and other vasculitides. We analysed the clinical efficacy and tolerability of LEF in a large cohort of patients with various vasculitides. METHODS. This was a retrospective analysis of patients who received LEF for treatment of their vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Study and in 3 additional centres from the Canadian vasculitis research network (CanVasc). RESULTS. Data for 93 patients were analysed: 45 had granulomatosis with polyangiitis (GPA), 8 microscopic polyangiitis (MPA), 12 eosinophilic granulomatosis with polyangiitis (EGPA), 14 giant-cell arteritis (GCA), 9 Takayasu’s arteritis (TAK), and 5 polyarteritis nodosa (PAN). The main reason for initiation of LEF was active disease (89%). LEF was efficacious for remission induction or maintenance at 6 months for 62 (67%) patients (64% with GCA, 89% with TAK, 80% with PAN, 69% with GPA, 75% with MPA, 33% with EGPA); 20% discontinued LEF before achieving remission because of persistent disease activity. Overall, 22 adverse events (gastrointestinal symptoms being the most common) led to drug discontinuation in 18 (19%) patients, of which 12 stopped LEF before month 6, before showing any benefit in 8/12 of these patients. CONCLUSION. Leflunomide can be an effective therapeutic option for various vasculitides, especially for non-severe refractory or relapsing ANCA-associated vasculitis or large-vessel vasculitis. No new safety signals for LEF were identified in this population.

Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are multisystem diseases of small blood vessels, collectively known as the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). This study explores the patient’s perspective on the use of glucocorticoids, which are still a mainstay of treatment in AAV. Patients with AAV from the UK, USA, and Canada were interviewed, using purposive sampling to include a range of disease manifestations and demographics. The project steering committee, including patient partners, designed the interview prompts and cues about AAV, its treatment, and impact on health-related quality of life. Interviews were transcribed and analysed to establish themes grounded in the data. A treatment-related code was used to focus analysis of salient themes related to glucocorticoid therapy. Fifty interviews were conducted. Individual themes related to therapy with glucocorticoids emerged from the data and were analysed. Three overarching themes emerged: (1) Glucocorticoids are effective at the time of diagnosis and during relapse, and withdrawal can potentiate a flare, (2) glucocorticoids are associated with salient emotional, physical, and social effects (depression, anxiety, irritation, weight gain and change in appearance, diabetes mellitus, effect on family and work); and (3) patient perceptions of balancing the risks and benefits of glucocorticoids. Patients identified the positive aspects of treatment with glucocorticoids; they are fast-acting and effective, but, they voiced concerns about adverse effects and the uncertainty of the dose-reduction process. These results may be informative in the development of novel glucocorticoid-sparing regimens., Sponsored by University of Oxford and the Vasculitis Clinical Research Consortium, with support from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874), the National Center for Research Resources (U54 RR019497); and the Office of Rare Diseases Research. Additional support for the work of the OMERACT vasculitis working group was received by a Patient-Centered Outcomes Research Institute Pilot Project Grant, the Medical Research Fund, Oxford, and the Oxfordshire Health Services Research Committee. Dr. Robson and Professor Luqmani are supported in part by the National Institute for Health Research Musculoskeletal Biomedical Research Unit, Oxford, UK. Dr. Milman was supported by a UCB/Canadian Rheumatology Association/Arthritis Society postgraduate rheumatology fellowship award and a research fellowship from the Department of Medicine at the Ottawa Hospital.

Objective.Among the challenges in conducting clinical trials in large-vessel vasculitis (LVV), including both giant cell arteritis (GCA) and Takayasu arteritis (TA), is the lack of standardized and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group initiated an international effort to develop and validate data-driven outcome tools for clinical investigation in LVV.Methods.An international Delphi exercise was completed to gather opinions from clinical experts on LVV-related domains considered important to measure in trials. Patient interviews and focus groups were completed to identify outcomes of importance to patients. The results of these activities were presented and discussed in a “Virtual Special Interest Group” using telephone- and Internet-based conferences, discussions through electronic mail, and an in-person session at the 2016 OMERACT meeting. A preliminary core set of domains common for all forms of LVV with disease-specific elements was proposed.Results.The majority of experts agree with using common outcome measures for GCA and TA, with the option of supplementation with disease-specific items. Following interviews and focus groups, pain, fatigue, and emotional effect emerged as health-related quality of life domains important to patients. Current disease assessment tools, including the Birmingham Vasculitis Activity Score, were found to be inadequate to assess disease activity in GCA and standardized assessment of imaging tests were felt crucial to study LVV, especially TA.Conclusion.Initial data from a clinician Delphi exercise and structured patient interviews have provided themes toward an OMERACT-endorsed core set of domains and outcome measures.

Outcome Measures in Rheumatology Conference (OMERACT) -- MAY 15-18, 2018 -- Terrigal, AUSTRALIA Gul, Ahmet/0000-0001-8219-3720; ALIBAZ-ONER, FATMA/0000-0002-6653-1758; Hill, Catherine/0000-0001-8289-4922; Mahr, Alfred/0000-0002-1564-9115 WOS:000484027700024 PubMed ID: 30877212 Objective. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group seeks to develop validated outcome measures for use in trials for large-vessel vasculitis (LVV). Methods. An international Delphi exercise conducted among investigators identified items considered important to measure active disease. In parallel, qualitative research with patients was conducted, including interviews and focus groups. Results. Next steps prioritized by the group for LVV include (1) defining disease states (remission, flare, and patient-acceptable symptom state) and (2) selection of patient-reported outcome tools. Conclusion. The ultimate goal is to develop an OMERACT-endorsed core set of outcome measures for use in clinical trials of LVV. Outcome Measures Rheumatol US Vasculitis Clinical Research Consortium (VCRC); NCATSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [U54 AR057319]; National Institute of Arthritis and Musculoskeletal and Skin DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54 AR057319]; National Center for Research ResourcesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [U54 RR019497]; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319, U54AR057319] Funding Source: NIH RePORTER This work was funded in part by the US Vasculitis Clinical Research Consortium (VCRC). The VCRC is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Science (NCATS). The VCRC is funded through collaboration between NCATS, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319), and has received funding from the National Center for Research Resources (U54 RR019497).

Background: ANCA-associated vasculitis (AAV) is a significant cause of morbidity and mortality. Meeting the challenges of aAV effectively requires patients to engage in self-management, including medical management, role management, and emotional management.1 Self-management is recognised as a key aspect of chronic disease management and forms an important part of the National Health Service 5-year forward plan and the UK strategy for rare diseases.2,3 Nonetheless, there has been limited specific research into the role of self-management in the aAV literature. Objectives: To explore experiences and views of self-management amongst aAV patients. Methods: A secondary analysis of all interview transcripts from a previous project exploring health-related quality of life in relation to aAV was performed.4 Deductive analysis was used to map appropriate areas discussed by patients to the self-management framework proposed by Lorig and Holman.1 inductive analysis was used to identify emergent themes that did not fit into this framework. Results: Interview data were collected from 50 patients with aAV (25 men), from the UK (n=18), USA (n=17) and Canada (n=15). Diagnoses included GPA (n=26), EGPA (n=17) and MPA (n=7). Thirty-four patients were diagnosed within the last 2 years and 16 were diagnosed more than 2 years ago.4 From the core tasks proposed in Lorig and Holman’s framework, patients with aAV appear to attribute particular importance to maintaining life roles and to a lesser extent medication management and dealing with the emotions of chronic disease. Core skills necessary to self-manage in aAV include learning to take action as part of self-efficacy, forming productive health-care partnerships, learning about decision making (requiring disease and self-awareness), utilising resources effectively, and problem-solving. Three themes emerged that were not included in Lorig and Holman’s framework that respondents related to self-management abilities including: 1) support received from family, support groups, and religion; 2) the influence of pre-morbid personality factors; 3) the role patients attributed to developing a foundation of specific aAV knowledge in their subsequent ability to self-manage. Conclusion: Patients with aAV self-manage in a variety of ways and their needs may change over time. Patients may benefit from support to help manage changing life roles and to deal with the challenges of having a chronic disease. Over time, support may need to shift focus onto core skills including recognising when to take action; forming effective partnerships with healthcare providers, family, and friends; adaptations to day-to-day changes in their condition; utilising resources appropriately; and strategies for problem-solving. References [1] Lorig, K.R. And Holman, H.R., 2003. Self-management education: history, definition, outcomes, and mechanisms. Annals of behavioral medicine, 26(1), pp.1-7. [2] NHS England. Five year forward view. Oct2014. Available from:https://www.england.nhs.uk/ourwork/futurenhs/ [3] UK Strategy for Rare Diseases. Department of Health,2013. [4] Robson, J.C., Dawson, J., Cronholm, P.F., Milman, N., Kellom, K.S., ashdown, S., Easley, E., Farrar, J.T., Gebhart, D., Lanier, G. AndMcAlear, C.A., 2018. Health-related quality of life in aNCA-associated vasculitis and item generation for a disease-specific patient-reported outcome measure. Patient related outcome measures, 9, p.17. Disclosure of interests: Tim Reynolds: None declared, Emma Dures Grant/research support from: Has previously received an independent learning grant from Pfizer, however the work has been completed and the grant has been closed., Sue ashdown: None declared, Peter Cronholm: None declared, Raashid Luqmani Grant/research support from: Roche, Vifor and GSK, Peter Merkel: None declared, Nataliya Milman: None declared, Jacqueline Peck: None declared, Joanna Robson: None declared

Objectives Our aim was to evaluate characteristics and prospective adverse aortic outcomes in a cohort of patients with non-infectious histological aortitis. Methods Patients with histological aortitis, diagnosed at the Ottawa Hospital after surgical repair of thoracic aortic aneurysms or dissections, consented to enrolment in a prospective observational cohort. Patients were assessed for an underlying inflammatory condition and followed prospectively with periodic clinical, laboratory and radiographic assessments. Aortic outcomes during follow-up included significant events, defined as new thoracic or abdominal aortic aneurysms, dissections, ruptures or other complications requiring aortic intervention, in addition to aortic branch ectasias, aneurysms and stenosis. Results Sixteen patients with histological aortitis from surgical procedures performed between 2010 and 2017 were included; nine had idiopathic and seven had secondary aortitis. Idiopathic patients were more likely to have smoked (100 vs 43%, P = 0.02) and had more associated arch or descending aortic aneurysms on pre-operative baseline imaging compared with secondary aortitis (6 vs 0, P = 0.01). At the median 3.6 years of follow-up, eight patients (50%) had 10 significant aortic events. The incidence of aortic dissection was higher in the first year post-surgery, compared with subsequent years, whereas incident aneurysms occurred throughout follow-up. Elevated inflammatory markers during follow-up trended towards association with accumulation of severe aortic damage. Conclusion This is the first reported prospective study in patients with histological aortitis. Within the limitations of a small cohort, we report a high incidence of aortic complications. Studies with a larger sample size and longer follow-up are needed to corroborate these findings.

Importance: Scurvy remains prevalent in certain populations, including addicts, people of low socioeconomic status, and the severely malnourished. It classically presents as follicular hyperkeratosis and perifollicular hemorrhage of the lower extremities, as well as bleeding in other areas such as the gingiva and joints. This case presentation and literature review highlights the common pathophysiological findings associated with scurvy and current methods of diagnosis and treatment. Observation: The patient described in this case presented with sudden oligoarthritis and purpura of the lower extremities. Following progression of the patient’s symptoms and a low vitamin C serum concentration, the patient was treated with vitamin C supplementation and dramatically improved. This was considered to be the result of an underlying vitamin C deficiency secondary to insufficient fruit and vegetable intake due to allergies. Conclusions and Relevance: This case highlights the importance of maintaining a high index of suspicion for scurvy in atypical presentations of purpura not better explained by another disease or in additional populations at high risk of vitamin C deficiency. Early diagnosis by either a primary care physician or dermatologist can expedite the treatment process and improve patient prognosis.

Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are multisystem diseases of the small blood vessels. Patients experience irreversible damage and psychological effects from AAV and its treatment. An international collaboration was created to investigate the impact of AAV on health-related quality of life (HRQoL), and develop a disease-specific patient-reported outcome measure to assess outcomes of importance to patients. Methods: Patients with AAV from the UK, USA, and Canada were interviewed to identify salient aspects of HRQoL affected by AAV. The study was overseen by a steering committee including four patient research partners. Purposive sampling of interviewees ensured representation of a range of disease manifestations and demographics. Inductive analysis was used to identify themes of importance to patients; these were further confirmed by a free-listing exercise in the US. Individual themes were recast into candidate items, which were scrutinized by patients, piloted through cognitive interviews and received a linguistic and translatability evaluation. Results: Fifty interviews, conducted to saturation, with patients from the UK, USA, and Canada, identified 55 individual themes of interest within seven broad domains: general health perceptions, impact on function, psychological perceptions, social perceptions, social contact, social role, and symptoms. Individual themes were constructed into >100 candidate questionnaire items, which were then reduced and refined to 35 candidate items. Conclusion: This is the largest international qualitative analysis of HRQoL in AAV to date, and the results have underpinned the development of 35 candidate items for a disease-specific, patient-reported outcome questionnaire., Sponsored by the University of Oxford, the Vasculitis Clinical Research Consortium and the University of Ottawa. With support from the Medical Research Fund, Oxford, the Oxfordshire Health Services Research Committee (Ref 1098), the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54 AR057319 and U01 AR51874), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research. Oxford University Innovation funded the translatability exercise. Additional support received by a Patient-Centred Outcomes Research Institute Pilot Project Grant.

Objectives : To study variations in Canadian clinical practice patterns for the management of ANCA-associated vasculitis (AAV) and identify points to consider for the development of national recommendations. Material and Methodology : A 30-item needs assessment questionnaire was sent to all members of the Canadian Vasculitis network (CanVasc), Canadian Rheumatology Association (CRA), Canadian Thoracic Society (CTS) and Canadian Society of Nephrology (CSN). Respondent characteristics, practice patterns, concerns and expectations were analyzed. Results : Among 132 physicians who followed at least 1 vasculitis patient and responded to the survey, 39% stated that they felt confident in their management of AAV. Several variations in practice were observed regarding diagnostic procedure, induction and maintenance treatments and use of biologics; some were due to logistic constraints (difficulties in access to some specific tests, drugs or care; lack of health care coverage for the costs). The top 5 topics for which recommendations are expected involve treatment for remission induction, maintenance, refractory disease, and relapse as well as biologics. Conclusion : Practice variations identified in this needs assessment survey will serve to formulate key questions for the development of CanVasc recommendations.

Objective The International Classification of Functioning, Disability and Health (ICF) is a framework and classification of health that describes health along 4 components: body functions, body structures, activities and participation, and contextual factors. This study examined the content of instruments that constitute the Outcome Measures in Rheumatology (OMERACT) core set of outcome measures for antineutrophil cytoplasmic antibody–associated vasculitis (AAV) by “mapping” them to the ICF. Methods The content of the instruments included in the AAV core set were linked to the ICF by 2 independent investigators according to previously established ICF linkage rules. Results The AAV core set includes 3 measures of disease activity (3 versions of the Birmingham Vasculitis Activity Score), 1 damage measure (Vasculitis Damage Index), 1 patient-reported outcome (Short Form 36 health survey), and death. Linking these instruments to the ICF revealed comprehensive coverage of the ICF components body functions and body structures, limited coverage of the ICF component activities and participation, and complete absence of coverage of contextual factors. Conclusion ICF was found to be useful for thematic characterization of a heterogeneous group of outcome measures for AAV, i.e., a group of complex medical conditions. Linking of the instruments selected for the OMERACT AAV core set of outcome measures to the ICF classification revealed limitations in the representation of constructs related to life impact of AAV, represented by the ICF components activities and participation and contextual factors. Further research and methods development are needed to better incorporate important aspects of functioning and health relevant to patients into clinical trials of AAV.

Objectives o finalise and validate a disease-specific patient-reported outcome (PRO) measure: the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire. Using a 35-item candidate questionnaire developed following 50 qualitative interviews in the UK, USA and Canada, a longitudinal survey was conducted to determine the final scale structure and validate the AAV-PRO. Methods Participants were recruited via Vasculitis UK and the Vasculitis Patient-Powered Research Network. The 35-item candidate questionnaire was completed at baseline and 3 months; UK participants completed the EuroQol-5D-5L (EQ-5D-5L), while US participants completed a test–retest exercise, 3–5 days after baseline. Scale structure was defined using exploratory factor analysis (EFA) and Rasch analysis. Convergent and known groups validity, test–retest reliability and longitudinal construct validity were assessed. Results here were 626 participants with AAV; >25% reporting ’active disease’. EFA and Rasch analysis supported a 29-item profile measure comprising six domains: ’organ-specific symptoms’, ’systemic symptoms’, ’treatment side effects’, ’social and emotional impact’, ’concerns about the future’ and ’physical function’. Mean domain scores were higher for participants with ’active disease’ versus ’remission’ (p Conclusions he AAV-PRO, a new disease-specific PRO measure for AAV, has good face and construct validity, is reliable, feasible and discriminates among disease states.

Objective.The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome assessment and defined them as “potential confounders and/or effect modifiers of outcomes in randomized controlled trials.” Subsequently, the CF Methods Group (CFMG) was formed to develop guidance on how to address CF in clinical trials.Methods.First, the CFMG conducted an e-mail survey of OMERACT working groups (WG) to analyze how they had addressed CF in outcome measurement so far. The results facilitated an informed discussion at the OMERACT 2016 CFMG Special Interest Group (SIG) session, with the aim of gaining preliminary consensus regarding an operational definition of CF and to make a first selection of potentially relevant CF.Results.The survey revealed that the WG had mostly used the OMERACT Handbook and/or the International Classification of Functioning, Disability and Health (ICF) definition. However, significant heterogeneity was found in the methods used to identify, refine, and categorize CF candidates. The SIG participants agreed on using the ICF as a framework along with the OMERACT Handbook definition. A list with 28 variables was collected including person-related factors and physical and social environments. Recommendations from the SIG guided the CFMG to formulate 3 preliminary projects on how to identify and analyze CF.Conclusion.New methods are urgently needed to assist researchers to identify and characterize CF that significantly influence the interpretation of results in clinical trials. The CFMG defined first steps to develop further guidance.

Objective.The antineutrophil cytoplasmic antibody–associated vasculitides (AAV) are multiorgan diseases. Patients with AAV report impairment in their health-related quality of life (HRQOL) and have different priorities regarding disease assessment compared with physicians. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group previously received endorsement for a core set of domains in AAV. Two approaches to measure patient-reported outcomes (PRO) were presented at OMERACT 2016.Methods.A novel 5-step tool was used to facilitate assessment of the instruments by delegates: the OMERACT Filter 2.0 Instrument Selection Algorithm, with a red-amber-green checklist of questions, including (1) good match with domain (face and content validity), (2) feasibility, (3) do numeric scores make sense (construct validity)?, (4) overall ratings of discrimination, and (5) can individual thresholds of meaning be defined? Delegates gave an overall endorsement. Three generic Patient-Reported Outcomes Measurement Information System (PROMIS) instruments (fatigue, physical functioning, and pain interference) and a disease-specific PRO, the AAV-PRO (6 domains related to symptoms and HRQOL), were presented.Results.OMERACT delegates endorsed the use of the PROMIS instruments for fatigue, physical functioning, and pain interference (87.6% overall endorsement) and the disease-specific AAV-PRO instrument (89.4% overall endorsement).Conclusion.The OMERACT Vasculitis Working Group gained endorsement by OMERACT for use of the PROMIS and the AAV-PRO in clinical trials of vasculitis. These instruments are complementary to each other. The PROMIS and the AAV-PRO need further work to assess their utility in longitudinal settings, including their ability to discriminate between treatments of varying efficacy in the setting of a randomized controlled trial.

BACKGROUND Idiopathic aortitis became recognized relatively recently, and the body of knowledge concerning this condition is scarce. We aimed to determine the frequency of idiopathic aortitis in aortic specimens, the clinical, laboratory and radiologic characteristics at diagnosis and during follow-up, and the approach to investigation, treatment and monitoring taken by the treating physicians. METHODS We identified cases of aortitis diagnosed on pathological specimens of the aorta between Jan. 1, 2003, and July 31, 2013, at The Ottawa Hospital by reviewing the hospital's pathology database. Charts of identified patients were reviewed, and data on patient demographic characteristics, clinical features, laboratory and imaging tests, treatment and outcomes were analyzed. RESULTS A total of 684 aortic specimens were analyzed during the study period; 47 cases of aortitis were identified, 32 of which were idiopathic. Twenty-one patients (66%) had complete imaging of branch vessels at baseline, 16 (76%) of whom had additional aortic or branch vessel lesions. Twelve patients (38%) received corticosteroids postoperatively. Over a mean follow-up period of 47.5 months, among the 12 patients (38%) who had complete imaging of branch vessels at least once, new aortic or branch lesions were diagnosed in 5 (42%); 3/32 patients (9%) required additional vascular surgery; and a new systemic condition was diagnosed in 2/32 (6%). INTERPRETATION Idiopathic aortitis is commonly discovered incidentally on examination of the pathological specimen following ascending aortic aneurysm repair. No guidelines exist for the investigation, treatment and follow-up of this condition, resulting in great variability of practice. Good-quality prospective studies are needed to address the many unanswered clinical questions regarding idiopathic aortitis and to allow formulation of more definitive recommendations.

The need to include patients' perspectives as key outcomes in clinical trials is widely accepted. No disease-specific patient-reported outcomes have been developed in Takayasu's arteritis. This project was designed to identify outcomes of importance to patients with Takayasu's arteritis during active disease and remission across 2 different cultures.Patients with Takayasu's arteritis from the US and Turkey were recruited to participate in semi-structured, one-on-one interviews or focus groups. The interviews and group sessions were recorded, transcribed, and entered into an Nvivo database. A line-by-line review of narrative data was used to develop themes describing the impact of Takayasu's arteritis on patients' life. US Patients were invited to freelist terms that they associated with disease states (active disease and remission). The Smith's Salience Index (SSI) was used to identify the most salient terms.Results. A total of 31 patients with Takayasu's arteritis participated in this study. Interviews and focus groups identified pain, fatigue, and emotional impact as common themes. Outcomes did not differ between the 2 countries. The most salient terms identified through freelisting were pain/discomfort and fatigue/low energy levels (SSI=0.56 and 0.33, respectively) during active disease and pain/discomfort and emotional impact (SSI=0.51 and 0.37, respectively) during remission.Patients with Takayasu's arteritis report a range of disease-specific symptoms across different cultures and disease states that are generally not specifically captured by generic patient-reported outcome tools currently used in research. Identifying disease-specific outcomes would advance clinical trials methodology to best capture the full spectrum of disease activity in Takayasu's arteritis.

Objectives: The existing set of outcomes for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) needs to incorporate views of outcome measure stakeholders to meet the current standards of outcome measurement proposed by the Outcome Measures in Rheumatology (OMERACT) initiative. This study identifies domains that clinical experts (one group of stakeholders) consider to be important to determining the impact of AAV using the International Classification of Functioning, Disability and Health (ICF), a framework that describes health along four components: body functions, body structures, activities and participation, and contextual factors.Method: An international group of clinicians with expertise in the clinical care of patients with vasculitis were identified through consultation with three major vasculitis societies. The relevant domains were determined using a three-round e-mail-based Delphi questionnaire.Results: Eighty-two clinicians were invited to participate in this study and 41 responded. Nineteen domains were identified as important by > 80% of participants: six body functions (energy, seeing, hearing, pain, respiratory, and renal function), seven body structures (peripheral nerves, eye, ear, nose, sinuses, lungs (and airways), and kidneys), three activities and participation (carrying out daily routine, remunerative employment, and recreation and leisure), and three environmental factors (medications, support and relationships, and health services, systems, and policies).Conclusions: Clinical experts focus on the physiological effects of AAV with less importance given to the effect of AAV on patients' activities and participation in life situations and the role of contextual factors. This study represents a step towards incorporating views of a range of stakeholders into disease assessment in AAV.

Objective.The rarity of large vessel vasculitis (LVV) is a major factor limiting randomized controlled trials in LVV, resulting in treatment choices in these diseases that are guided mainly by observational studies and expert opinion. Further complicating trials in LVV is the absence of validated and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group initiated the Large Vessel Vasculitis task force in 2009 to develop data-driven, validated outcome tools for clinical investigation in LVV. This report summarizes the progress that has been made on a disease activity assessment tool and patient-reported outcomes in LVV as well as the group’s research agenda.Methods.The OMERACT LVV task force brought an international group of investigators and patient research partners together to work collaboratively on developing outcome tools. The group initially focused on disease activity assessment tools in LVV. Following a systematic literature review, an international Delphi exercise was conducted to obtain expert opinion on principles and domains for disease assessment. The OMERACT vasculitis working group’s LVV task force is also conducting qualitative research with patients, including interviews, focus groups, and engaging patients as research partners, all to ensure that the approach to disease assessment includes measures of patients’ perspectives and that patients have input into the research agenda and process.Results.The preliminary results of both the Delphi exercise and the qualitative interviews were discussed at the OMERACT 12 (2014) meeting and the completion of the analyses will produce an initial set of domains and instruments to form the basis of next steps in the research agenda.Conclusion.The research agenda continues to evolve, with the ultimate goal of developing an OMERACT-endorsed core set of outcome measures for use in clinical trials of LVV.

The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

Objective.Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients’ perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV.Methods.Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV.Results.The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility.Conclusion.The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.

Objective.The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada.Methods.Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings. Quality of supporting evidence for each therapeutic recommendation was graded. The full working group as well as additional reviewers, including patients, reviewed the developed therapeutic recommendations and nontherapeutic statements using a modified 2-step Delphi technique and through discussion to reach consensus.Results.Nineteen recommendations and 17 statements addressing general AAV diagnosis and management were developed, as well as appendices for practical use, for rheumatologists, nephrologists, respirologists, general internists, and all other healthcare professionals more occasionally involved in the management of patients with AAV in community and academic practice settings.Conclusion.These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.

Source Citation Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377:317-28. 28745999

The conduct of randomized controlled trials for vasculitis, especially for the antineutrophil cytoplasmic antibody-associated vasculitides [AAV, granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis], has been greatly advanced by the development, use, and acceptance of validated outcome measures. Trials have subsequently provided the opportunity to validate and refine reliable, valid outcome measures for these multisystemic and relapsing rare diseases. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group was formed in 2004 to foster development of validated and widely accepted outcomes in vasculitis using data-driven analyses, a dedication to building consensus, and adherence to, and guidance by, the principles of the OMERACT approach. This work led to the endorsement by OMERACT of the core set of domains and associated outcome measures for AAV. Next steps for the study of existing outcome tools in AAV include better definition of response criteria through development of more data-driven weighting of the elements of activity and damage assessment. The Working Group is now also embarking on a series of linked projects to develop validated patient-reported outcomes for use in clinical research in vasculitis. Additionally, the Working Group is studying how current methods of disease assessment and plans for new outcomes can be informed by the conceptual framework of the International Classification of Function of the World Health Organization. The success of the Group’s work in AAV has also led to a formal process for developing outcomes for the large vessel vasculitides (Takayasu arteritis and giant cell arteritis) and Behçet disease.

Objective Cocaine is known to cause thrombotic complications. Its use has also been associated with a variety of rheumatologic manifestations, most notably cutaneous vasculopathy. We report clinical features and laboratory findings of cocaine-related cutaneous vasculopathy. Methods Here we describe 8 patients with cocaine-related cutaneous vasculopathy. Results Our patients most commonly presented with purpuric lesions and ulcers with areas of skin necrosis. Extracutaneous features included fatigue and arthritis in most patients, as well as weight loss in 3 patients, pneumonia in 3, diffuse reactive lymphadenopathy in 1, and acute upper airway obstruction in 2. Laboratory abnormalities included elevated inflammatory markers and positive perinuclear antineutrophil cytoplasmic antibodies (ANCAs) in all patients, and antimyeloperoxidase antibodies in 7 of 8 patients. Cytoplasmic ANCA was positive in 5 of 8, equivocal in 2 of 8, and negative in 1 of 8 patients. Anti–proteinase 3 antibodies were found in 6 of 8 patients. Six of 8 patients had positive antinuclear antibodies and 5 of 8 had positive anti–double-stranded DNA antibodies (4 of 5 were at low titers). Two patients previously thought to have systemic lupus erythematosus had low complement levels. Lupus anticoagulant was positive in 3 of 8 and equivocal in 5 of 8. Anticardiolipin IgG was positive in 1 of 8 and IgM was positive in 6 of 8; β2-glycoprotein I IgM was positive in 2 of 8. Cold agglutinins were strongly positive in 6 of 6 patients in whom they were measured. Skin disease improved in 3 patients who appeared to have stopped using cocaine. It was chronic and progressive in 4 patients who continued to use cocaine, 2 of whom died presumably due to multidrug overdose. Conclusion This report outlines clinical features and distinctive laboratory findings that, when present in the right clinical setting, should prompt consideration of cocaine-related cutaneous vasculopathy.

Objective Explore the potential use of a cytokine panel as biochemical markers of disease activity in rheumatoid arthritis (RA) patients. Design and methods 57 adult RA patients were assessed using five validated clinical disease activity tools: Health Assessment Questionnaire (HAQ), standard 28-joint Disease Activity Score (DAS28), DAS28 using C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), and Simple Disease Activity Index (SDAI). Plasma cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL1α, IL1β, MCP1, and EGF) were measured in 47 of the 57 patients and correlated with clinical indicators. Results We found significant correlations between plasma levels of IL-6 and all clinical measures of disease activity; Spearman coefficients (p values) were: HAQ: 0.347(0.017); DAS28: 0.409(0.005); DAS-CRP: 0.378(0.011); CDAI: 0.312(0.033); SDAI: 0.310(0.039); ESR: 0.448(0.002); and CRP: 0.513(0.001). IFN-γ also correlated with DAS-CRP: 0.309(0.039) and SDAI: 0.301(0.044). Furthermore, the levels of IL-6 and IFN-γ increased significantly with worsening disease, as defined by the European League Against Rheumatism (EULAR) classification of disease activity. Conclusion A significant correlation between plasma levels of IL-6 and clinical disease activity in patients with RA suggests a future role of IL6 as a disease activity marker.

To the Editor: A 41-year-old woman with psoriatic arthritis developed watery diarrhea 3 days after starting diclofenac. She had been taking celecoxib for 3 years without having diarrhea. She also started taking etanercept 5 months prior to presentation. She stopped the diclofenac after 2 weeks of diarrhea, and her bowel movements returned to normal. She restarted the diclofenac 1 week later because of worsening joint pain, and her diarrhea recurred after 2 days. Her symptoms persisted despite permanently discontinuing the diclofenac 3 weeks later. Four months after the onset of symptoms, she required admission to a hospital for dehydration. The etanercept was stopped. Her laboratory investigations, including complete blood count, electrolytes, erythrocyte sedimentation rate, albumin, kidney and liver function tests, tissue transglutaminase IgA antibody screen, and stool cultures, were all normal. A computed tomography scan of the abdomen was nondiagnostic. A colonoscopy revealed only mild erythema at the rectosigmoid junction. The pathologic examination of the biopsy specimen revealed marked thickening of the subepithelial collagen layer, and markedly increased numbers of inflammatory cells within the surface epithelium, consistent with severe collagenous colitis (Figure 1). Figure 1. Patient’s biopsy samples. A: Hematoxylin and eosin stain, … Address correspondence to Dr. Kraag; E-mail: grkraag{at}ottawahospital.on.ca