Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV.

Methods: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained.

Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener's): Distinct Patient Subsets.

Objective: To examine the relationship of antineutrophil cytoplasmic antibody (ANCA) type and ANCA-associated vasculitis (AAV) diagnosis with demographic features, disease manifestations, and clinical outcomes. We focused on patients who account for the differences between ANCA type and disease type classifications: anti-myeloperoxidase (MPO)-ANCA-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener's) (GPA).

Methods: We performed a pooled analysis of the Wegener's Granulomatosis Etanercept Trial and the Rituximab in ANCA-Associated Vasculitis trial comparing patients with MPO-ANCA-positive GPA and patients with ANCA-negative GPA to patients with proteinase 3 (PR3)-ANCA-positive GPA and patients with MPO-ANCA-positive microscopic polyangiitis (MPA).

Patient-Reported Outcomes in Glomerular Disease.

Incorporation of the patient perspective into research and clinical practice will enrich our understanding of the status and management of patients with glomerular disease and may result in therapies that better address patient needs. In recent years, the importance of the patient experience of glomerular disease has become clear, and significant efforts have been undertaken to systematically capture and describe the patient's disease experience. Patient-reported outcome instruments provide a means to assess the patient's experience in a quantitative manner, thus enabling for comparisons within and between patients.

Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population.

Objective: To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden.

Methods: We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year.

Visual Complications in Patients with Biopsy-proven Giant Cell Arteritis: A Population-based Study.

Objective: To study the clinical and laboratory characteristics of patients with biopsy-proven giant cell arteritis (GCA) with visual complications, and to evaluate the incidence rate of visual complications in GCA compared to the background population.

Methods: Data from 840 patients with GCA in the county of Skåne, Sweden, diagnosed between 1997 and 2010, were used for this analysis. Cases with visual complications were identified from a diagnosis registry and confirmed by a review of medical records.

Using Mass Spectrometry to Quantify Rituximab and Perform Individualized Immunoglobulin Phenotyping in ANCA-Associated Vasculitis.

Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring (TDM) without relying on mAb specific reagents will be needed. In this study we demonstrate that liquid-chromatography-mass spectrometry (LC-MS) can be used to perform TDM of mAbs in the same manner as smaller nonbiologic drugs.

The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network.

Background: Among the unique features of the Rare Diseases Clinical Research Network (RDCRN) Program is the requirement for each Consortium to include patient advocacy groups (PAGs) as research partners. This development has transformed the work of the RDCRN and is a model for collaborative research. This article outlines the roles patients and PAGs play in the RDCRN and reports on the PAGs' impact on the Network's success.

Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials.

Importance: Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker.

Objective: To evaluate the efficacy of macitentan in reducing the number of new digital ulcers in patients with systemic sclerosis.

The Birmingham Vasculitis Activity Score as a Measure of Disease Activity in Patients with Giant Cell Arteritis.

Objective: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) in the assessment of disease activity in giant cell arteritis (GCA).

Methods: Patients with GCA enrolled in a prospective, multicenter, longitudinal study with symptoms of active vasculitis during any visit were included. Spearman's rank correlation was used to explore the association of the BVAS with other measures of disease activity.

Severe Small-Vessel Vasculitis Temporally Associated With Administration of Ustekinumab.

Vasculitis may be caused by infection, medications, systemic diseases, malignancy, or occur as an idiopathic condition. In cases of drug-induced vasculitis, it is essential to identify and discontinue the culprit medication. As novel agents are approved through clinical trials, some rare events, including vasculitis, may not become apparent until wider use, and rigorous post-marketing surveillance for new medications is important.

Using patient-reported outcomes and PROMIS in research and clinical applications: experiences from the PCORI pilot projects.

Purpose: The field of patient-centered outcomes research (PCOR) continues to develop. Patient-reported outcomes and, in particular the Patient-Reported Outcomes Measurement Information System (PROMIS) contribute complementary data to clinician-derived outcomes traditionally used in health decision-making. However, there has been little work to understand how PROMIS measures may inform or be integrated into PCOR or clinical applications.

Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3.

Objective: Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse.

Methods: Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used.

Trends in Long-Term Outcomes Among Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Renal Disease.

Objective: It is still not clear how advances in the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have impacted long-term outcomes. We undertook this study to examine changes over 25 years in long-term clinical outcomes, including the impact of renal function at diagnosis (a potential marker of time to disease detection) and the duration of cyclophosphamide use in AAV patients with renal involvement.

Methods: We included ANCA-positive patients with biopsy-proven AAV diagnosed between 1985 and 2009 who were followed up in the Glomerular Disease Collaborative Network inception cohort.

The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis.

Objective: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).

Methods: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc.

The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis.

Objective: Early diffuse cutaneous systemic sclerosis (dcSSc) is characterized by rapid changes in the skin and internal organs. The objective of this study was to develop a composite response index in dcSSc (CRISS) for use in randomized controlled trials (RCTs).

Methods: We developed 150 paper patient profiles with standardized clinical outcome elements (core set items) using patients with dcSSc.

Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type.

Objective: To evaluate whether the classification of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) according to ANCA type (anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO) antibodies) predicts treatment response.

Methods: Treatment responses were assessed among patients enrolled in the Rituximab in ANCA-associated Vasculitis trial according to both AAV diagnosis (granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA)) and ANCA type (PR3-AAV/MPO-AAV). Complete remission (CR) was defined as disease activity score of 0 and successful completion of the prednisone taper.

A small n sequential multiple assignment randomized trial design for use in rare disease research.

Background: Clinical trials in rare diseases are difficult to conduct due to the limited number of patients available with each disorder. We developed a Phase 2 trial which is a small n sequential multiple assignment randomized trial (snSMART) design to test several treatments for a rare disease for which no standard therapy exists.

Purpose: This paper illustrates the design, sample size estimation and operating characteristics of an snSMART.

Current Status, Goals, and Research Agenda for Outcome Measures Development in Behçet Syndrome: Report from OMERACT 2014.

Objective: There is an unmet need for reliable, validated, and widely accepted outcomes and outcome measures for use in clinical trials in Behçet syndrome (BS). Our report summarizes initial steps taken by the Outcome Measures in Rheumatology (OMERACT) vasculitis working group toward developing a core set of outcome measures for BS according to the OMERACT methodology, including the OMERACT Filter 2.0, and discussions during the first meeting of the BS working group held during OMERACT 12 (2014).

Exploration, Development, and Validation of Patient-reported Outcomes in Antineutrophil Cytoplasmic Antibody-associated Vasculitis Using the OMERACT Process.

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.

Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients and systematic review of the literature.

Background: Published small case series suggest that inflammatory bowel disease [IBD; Crohn's disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur more frequently than would be expected by chance.

Objectives: To describe this association by an analysis of a large cohort of carefully studied patients and through a systematic literature review.

Methods: Patients with both IBD and vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc) centers and/or in the University of Toronto's IBD clinic were included in this case series.

Comparison of Treatment Response in Idiopathic and Connective Tissue Disease-associated Pulmonary Arterial Hypertension.

Rationale: Studies suggest that patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) have a poorer treatment response to therapies for PAH compared with patients with idiopathic PAH (IPAH), but individual randomized controlled trials (RCTs) have been underpowered to examine differences within these subgroups.

Objectives: To compare the effect of therapy for PAH in CTD-PAH versus IPAH.

Methods: We obtained individual participant data from phase III placebo-controlled RCTs of therapies for PAH submitted to the U.

Update on Outcome Measure Development for Large Vessel Vasculitis: Report from OMERACT 12.

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.

Adverse Events in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Objective: Patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment-related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences.

Methods: Individual patient-level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration.