A study of implementation factors for a novel approach to clinical trials: constructs for consideration in the coordination of direct-to-patient online-based medical research.

Background: Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g.

Assessment of Damage in Takayasu's Arteritis.

Objectives: To evaluate damage and clinical characteristics associated with damage in Takayasu's arteritis (TAK).

Methods: Patients with TAK enrolled in a multicentre, prospective, observational study underwent standardized damage assessment every 6 months using the Vasculitis Damage Index (VDI) and the Large-Vessel Vasculitis Index of Damage (LVVID).

Results: The study included 236 patients with TAK: 92% female, 81% Caucasian; median (25th, 75th percentile) disease duration = 2.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Introduction: Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV.

Methods: The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission.

Mitochondrial-mediated inflammation and platelet activation in giant cell arteritis.

Markers of extracellular mitochondria are present in giant cell arteritis (GCA) patients. However, their role in promoting inflammation and platelet activation is no known. To investigate this, isolated mitochondria were opsonized with plasma from GCA patients or healthy individuals and incubated with peripheral blood mononuclear cells (PBMCs) or platelets and assessed for inflammatory cytokine production and platelet activation.

Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial.

Objective: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab.

Ocular manifestations of ANCA-associated vasculitis.

Objectives: ANCA-associated vasculitis (AAV) is a group of multisystem diseases that can have several ocular manifestations. There are published data on ocular manifestations of granulomatosis with polyangiitis (GPA), but few for eosinophilic granulomatosis with polyangiitis (EGPA) or microscopic polyangiitis (MPA). There is little information concerning chronicity, complications, and association with other cranial manifestations of AAV.

Poor Patient-Reported Outcomes and Impaired Work Productivity in Patients With Inflammatory Bowel Disease in Remission.

Background And Aims: This study aimed to evaluate associations between disease severity, patient-reported outcomes (PROs), and work productivity in patients with inflammatory bowel disease (IBD [Crohn's disease (CD) and ulcerative colitis (UC)]).

Methods: Patients diagnosed with CD or UC enrolled in CorEvitas' IBD Registry (May 2017 to September 2019) were included (N = 1543; CD, n = 812; UC, n = 731). Disease severity was assessed using the Harvey-Bradshaw Index (CD) and partial Mayo Score (UC); psychosocial PROs (Patient-Reported Outcomes Measurement Information System [PROMIS]) and work productivity (Work Productivity and Activity Impairment [WPAI]) were assessed.

Neutrophil activation in patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis.

Objective: To assess markers of neutrophil activation such as calprotectin and N-formyl methionine (fMET) in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and large-vessel vasculitis (LVV).

Methods: Levels of fMET, and calprotectin, were measured in the plasma of healthy controls (n=30) and patients with AAV (granulomatosis with polyangiitis (GPA, n=123), microscopic polyangiitis (MPA, n=61)), and LVV (Takayasu's arteritis (TAK, n=58), giant cell arteritis (GCA, n=68)), at times of remission or flare. Disease activity was assessed by physician global assessment.

Self-Reported Data and Physician-Reported Data in Patients With Eosinophilic Granulomatosis With Polyangiitis: Comparative Analysis.

Background: Patient-based registries can help advance research on rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex multiorgan form of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.

Objective: The aim of this study is to compare patient-reported and physician-reported data on manifestations, treatments, and outcomes for patients with EGPA.

Methods: We completed a comparative analysis of patients ≥18 years with EGPA in Canada and the United States from the following 2 cohorts: (1) The Vasculitis Patient-Powered Research Network (VPPRN), a self-enrolled secure portal with patient-entered data updated quarterly (2014-2019) and (2) the Vasculitis Clinical Research Consortium (VCRC) observational studies, a physician-entered database (2003-2019) of patients who fulfilled the 1990 American College of Rheumatology classification criteria for EGPA.

Clinical Manifestations and Long-Term Outcomes of Eosinophilic Granulomatosis With Polyangiitis in North America.

Objective: To describe clinical manifestations and outcomes in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in North America.

Methods: Analysis of patients aged 18 years or older who fulfilled the 1990 American College of Rheumatology Classification Criteria for EGPA enrolled in the Vasculitis Clinical Research Consortium from 2003 to 2019. Main clinical characteristics, treatments, outcomes, and accumulated damage were studied.

Diagnostic delays in vasculitis and factors associated with time to diagnosis.

Background: Patients with vasculitis, a set of rare diseases, encounter delays in obtaining an accurate diagnosis which can lead to substantial morbidity and increased mortality. This study sought to describe the diagnostic journey of patients with vasculitis and identify factors associated with time to diagnosis.

Methods: Patients with vasculitis enrolled in an online registry completed a two-stage study: Stage 1: survey of open-ended questions about patients' diagnostic journeys and perceived factors associated with rapid or delayed diagnosis; Stage 2: survey with specific questions based on data from Stage 1 and additional investigator-identified factors.

Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis.

Objective: Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). This study was undertaken to examine longitudinal changes in the nasal microbiome in association with relapse in GPA patients.

Methods: Bacterial 16S ribosomal RNA gene sequencing was performed on nasal swabs from 19 patients with GPA who were followed up longitudinally for a total of 78 visits, including 9 patients who experienced a relapse and 10 patients who remained in remission.

Efficacy of leflunomide in the treatment of vasculitis.

Objectives: 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).

Sequence-Based Screening of Patients With Idiopathic Polyarteritis Nodosa, Granulomatosis With Polyangiitis, and Microscopic Polyangiitis for Deleterious Genetic Variants in ADA2.

Objective: Deficiency of adenosine deaminase 2 (DADA2) is a monogenic form of vasculitis that can resemble polyarteritis nodosa (PAN). This study was undertaken to identify potential disease-causing sequence variants in ADA2 in patients with idiopathic PAN, granulomatosis with polyangiitis (GPA), or microscopic polyangiitis (MPA).

Methods: Patients with idiopathic PAN (n = 118) and patients with GPA or MPA (n = 1,107) were screened for rare nonsynonymous variants in ADA2 using DNA sequencing methods.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis.

Objectives: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.

Methods: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months.

Patterns of clinical presentation in Takayasu's arteritis.

Objective: Takayasu's arteritis (TAK) is a clinically heterogenous disease. Patterns of clinical presentation in TAK at diagnosis have not been well described, and a "triphasic pattern" of constitutional symptoms evolving into vascular inflammation and fibrosis has been reported but never systematically evaluated.

Methods: Patients with TAK were prospectively recruited from the National Institutes of Health (NIH) and the Vasculitis Clinical Research Consortium (VCRC).

Harnessing health plan enrollee data to boost membership in patient-powered research networks.

Background: Patient-powered research networks (PPRNs) have been employing and exploring different methods to engage patients in research activities specific to their conditions. One way to intensify patient engagement is to partner with payer stakeholders. The objective of this study was to evaluate the effectiveness of two common payer-initiated outreach methods (postal mail versus email) for inviting prospective candidates to participate in their initiatives.

Outcome Measures in Large Vessel Vasculitis: Relationship Between Patient-, Physician-, Imaging-, and Laboratory-Based Assessments.

Objective: To assess the relationship between measures of disease assessment in patients with large vessel vasculitis.

Methods: Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular F-fluorodeoxyglucose-positron emission tomography activity).

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

Objectives: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions.

Methods: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories.

Evaluation of Potential Serum Biomarkers of Disease Activity in Diverse Forms of Vasculitis.

Objective: We evaluated potential circulating biomarkers of disease activity in giant cell arteritis (GCA), Takayasu arteritis (TA), polyarteritis nodosa (PAN), and eosinophilic granulomatosis with polyangiitis (EGPA).

Methods: A panel of 22 serum proteins was tested in patients enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies of GCA, TA, PAN, or EGPA. Mixed models were used for most analyses.

Patterns of Arterial Disease in Takayasu Arteritis and Giant Cell Arteritis.

Objective: To identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA).

Methods: Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large-vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories.

Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.

Objective: To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort.

Methods: Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.

Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis.

Objectives: To describe tracheobronchial disease in patients with granulomatosis with polyangiitis (GPA) and evaluate the utility of dynamic expiratory CT to detect large-airway disease.

Methods: Demographic and clinical features associated with the presence of subglottic stenosis (SGS) or endobronchial involvement were assessed in a multicentre, observational cohort of patients with GPA. A subset of patients with GPA from a single-centre cohort underwent dynamic chest CT to evaluate the airways.