ExploriNg DUrable Remission with Rituximab in ANCA-associatEd vasculitis (ENDURRANCE trial): protocol for a randomised controlled trial.

INTRODUCTION: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only. METHODS AND ANALYSIS: This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses. ETHICS AND DISSEMINATION: This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03942887.

Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients.

Objectives: Diagnosing patients with ANCA-associated vasculitis (AAV) can be challenging owing to its rarity and complexity. Diagnostic delay can have severe consequences, such as chronic organ damage or even death. Given that few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the diagnostic phase. Methods: This retrospective, observational study of electronic medical records data in hospitals focused on diagnostic procedures during the first assessment until diagnosis. Results: We included 230 AAV patients from nine hospitals. First assessments were mainly performed by a specialist in internal medicine (52%), pulmonology (14%), ENT (13%) or rheumatology (10%). The overall median time to diagnosis was 13 [interquartile range: 2-49] days, and in patients primarily examined by a specialist in internal medicine it was 6 [1-25] days, rheumatology 14 [4-45] days, pulmonology 15 [5-70] days and ENT 57 [16-176] days (P = 0.004). Twenty-two of 31 (71%) patients primarily assessed by a specialist in ENT had non-generalized disease, of whom 14 (64%) had ENT-limited activity. Two hundred and nineteen biopsies were performed in 187 patients (81%). Histopathological support for AAV was observed in 86% of kidney biopsies, 64% of lung biopsies and 34% of ENT biopsies. Conclusion: In The Netherlands, AAV is diagnosed and managed predominantly by internal medicine specialists. Diagnostic delay was associated with non-generalized disease and ENT involvement at presentation. Additionally, ENT biopsies had a low diagnostic yield, in contrast to kidney and lung biopsies. Awareness of this should lead to more frequent consideration of AAV and early referral for a multidisciplinary approach when AAV is suspected.

COVID-box Experiences of Patients and Health Care Professionals (COVID-box Project): Single-Center, Retrospective, Observational Study.

BACKGROUND: During the COVID-19 pandemic, several home monitoring programs have described the success of reducing hospital admissions, but only a few studies have investigated the experiences of patients and health care professionals. OBJECTIVE: The objective of our study was to determine patients' and health care professionals' experiences and satisfaction with employing the COVID-box. METHODS: In this single-center, retrospective, observational study, patients and health care professionals were asked to anonymously fill out multiple-choice questionnaires with questions on a 5-point or 10-point Likert scale. The themes addressed by patients were the sense of reassurance and safety, experiences with teleconsultations, their appreciation for staying at home, and the instructions for using the COVID-box. The themes addressed by health care professionals who treated patients with the COVID-box were the characteristics of the COVID-box, the technical support service and general satisfaction, and their expectations and support for this telemonitoring concept. Scores were interpreted as insufficient (≤2 or ≤5, respectively), sufficient (3 or 6-7, respectively), or good (≥4 or ≥8, respectively) on a 5-point or 10-point Likert scale. RESULTS: A total of 117 patients and 25 health care professionals filled out the questionnaires. The median score was 4 (IQR 4-5) for the sense of safety, the appreciation for staying at home, and experiences with teleconsultations, with good scores from 76.5% (88/115), 86% (56/65), and 83.6% (92/110) of the patients, respectively. Further, 74.4% (87/117) of the patients scored the home monitoring program with a score of ≥8. Health care professionals scored the COVID-box with a minimum median score of 7 (IQR 7-10) on a 10-point scale for all domains (ie, the characteristics of the COVID-box and the technical support service and general satisfaction). For the sense of safety, user-friendliness, and additional value of the COVID-box, the median scores were 8 (IQR 8-10), 8 (IQR 7-9), and 10 (IQR 8-10), respectively, with good scores from 86% (19/22), 75% (15/20), and 96% (24/25) of the health care professionals, respectively. All health care professionals (25/25, 100%) gave a score of ≥8 for supporting this home monitoring concept, with a median score of 10 (IQR 10-10). CONCLUSIONS: The positive experiences and satisfaction of involved users are key factors for the successful implementation of a novel eHealth solution. In our study, patients, as well as health care professionals, were highly satisfied with the use of the home monitoring program-the COVID-box project. Remote home monitoring may be an effective approach in cases of increased demand for hospital care and high pressure on health care systems.

Clinical Practice Audit on the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in the Netherlands.

INTRODUCTION: Managing complex and rare systemic autoimmune diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) can be challenging and is often accompanied by undesirable variations in clinical practice. Adequate understanding of clinical practice can help identify essential issues to improve the care for AAV patients. Therefore, we studied the real-life management and outcomes of AAV patients in the Netherlands. METHODS: In this cohort study, we investigated clinical practice in university and nonuniversity teaching hospitals with respect to patients with a clinical diagnosis of AAV. We retrospectively collected clinical data encompassing clinical variables, medication details, and outcome parameters. RESULTS: Data of 230 AAV patients were collected in 9 Dutch hospitals. Of these, 167 patients (73%) were diagnosed with granulomatosis with polyangiitis, 54 (24%) with microscopic polyangiitis and 9 (4%) with eosinophilic granulomatosis with polyangiitis. One hundred sixty-six patients (72%) had generalized disease. The median year of diagnosis was 2013 (range 1987-2018). Besides steroids, oral cyclophosphamide was the most used drug (50%) for induction therapy and azathioprine (68%) for maintenance therapy. Adverse outcomes were major infections in 35%, major relapses in 23%, malignancy in 10%, major cardiovascular events in 8%, and end-stage renal disease in 7%. CONCLUSION: Oral cyclophosphamide was the most frequently used induction therapy, azathioprine for maintenance therapy; over time, the use of rituximab is increasingly employed. Major infection and relapses are the most prevalent adverse outcomes. This audit resulted in important indicators for treatment of AAV patients that can be implemented for future, national audits to improve the outcomes of AAV patients.

PR3-ANCAs predict relapses in ANCA-associated vasculitis patients after rituximab.

BACKGROUND: The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI). METHODS: This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19+ B-cell status and relapses were assessed >2 years. RESULTS: Patients (31/110) relapsed within 2 years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n = 29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n = 49) and reappearance of PR3-ANCAs (n = 10) associated significantly with more relapses (37%, P = 0.002 and 50%, P = 0.002). Patients with incomplete B-cell depletion (n = 11) had significantly more relapses (54%) as compared with patients with B-cell depletion [n = 76 (26%), P = 0.02]. Also, patients with repopulation of B cells (n = 58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [n = 27 (15%), P = 0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation. CONCLUSIONS: Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX.

Telemonitoring for Patients With COVID-19: Recommendations for Design and Implementation.

Despite significant efforts, the COVID-19 pandemic has put enormous pressure on health care systems around the world, threatening the quality of patient care. Telemonitoring offers the opportunity to carefully monitor patients with a confirmed or suspected case of COVID-19 from home and allows for the timely identification of worsening symptoms. Additionally, it may decrease the number of hospital visits and admissions, thereby reducing the use of scarce resources, optimizing health care capacity, and minimizing the risk of viral transmission. In this paper, we present a COVID-19 telemonitoring care pathway developed at a tertiary care hospital in the Netherlands, which combined the monitoring of vital parameters with video consultations for adequate clinical assessment. Additionally, we report a series of medical, scientific, organizational, and ethical recommendations that may be used as a guide for the design and implementation of telemonitoring pathways for COVID-19 and other diseases worldwide.