Glucocorticoid Minimization in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An International Survey of Clinicians

Rationale & ObjectiveResearch in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians would accept as the lowest glucocorticoid dosing that could be used in induction therapy for AAV.Study DesignInternational, online surveySetting & ParticipantsClinicians in various countries, with experience in managing vasculitis.Exposure and OutcomesSurvey questions to gauge interest and preferences in studying an induction of remission regimen for severe AAV using only 2 or 4 weeks of glucocorticoids, without avacopan. Data collected included general opinions about standard of care for induction agents, glucocorticoids and avacopan. Respondents were presented with three candidate trial designs, two of which proposed a combination of cyclophosphamide and rituximab induction.Analytical ApproachUsing a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen will be safe and effective, and their willingness to randomize into the trial.ResultsThere were 210 respondents to the survey. The candidate trials were rated moderate-to-high for usefulness to demonstrate safety and efficacy (scores 6-7/10), and moderate (scores 5-6/10) for willingness to randomize. Four weeks glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4 weeks glucocorticoids was the most preferred design. 42% of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients.LimitationsRepresentativeness of survey sample and generalisability of findings.ConclusionsCombination cyclophosphamide-rituximab may be the ideal way of studying minimal glucocorticoid use in severe AAV. Given its increasing uptake, incorporating avacopan into a potential trial design would be important.