■抗中性粒细胞胞浆抗体相关血管炎(AAV)的研究集中在降低治疗毒性,特别是通过减少糖皮质激素的暴露。许多国家没有广泛使用糖皮质激素保留疗法,例如阿瓦科潘。患者暴露于高剂量的糖皮质激素。关于临床医生应该接受什么作为可用于AAV诱导治疗的最低糖皮质激素剂量的数据很少。
■国际,在线调查。
■各国具有治疗血管炎经验的临床医生。
■调查问题,以评估研究仅使用2或4周糖皮质激素而不使用阿瓦科潘的重度AAV诱导缓解方案的兴趣和偏好。收集的数据包括关于诱导剂护理标准的一般意见,糖皮质激素,和avacopan.向受访者展示了3种候选试验设计,其中2提出了环磷酰胺和利妥昔单抗的联合诱导。
■使用10点的李克特量表,受访者对每个候选试验的有效性进行排名,以证明最低限度的糖皮质激素方案是否安全有效,以及他们随机进入试验的意愿.
■该调查有210名受访者。候选试验被评为中等至高的有用性,以证明安全性和有效性(得分6-7/10),随机意愿中等(得分5-6/10)。糖皮质激素持续时间4周优先于2周,环磷酰胺-利妥昔单抗联合4周糖皮质激素是最优选的设计.42%的受访者认为必须将avacopan纳入最小GC试验设计中才能招募患者。
■调查样本的代表性和调查结果的普遍性。
■联合使用环磷酰胺-利妥昔单抗可能是研究重度AAV中少量使用糖皮质激素的理想方法。鉴于其不断增加的吸收,将avacopan纳入潜在的试验设计非常重要.
抗中性粒细胞胞浆抗体相关血管炎(AAV)的研究集中在使用较少的糖皮质激素来限制副作用。在许多国家还没有新的限制糖皮质激素使用的药物。需要研究寻找其他减少糖皮质激素暴露的方法来治疗AAV,但目前还不清楚如何最好地实现这一目标。我们对有治疗AAV经验的医生进行了一项调查,并让他们对广泛使用的治疗方法与2或4周糖皮质激素的不同组合进行分级。我们发现2剂量环磷酰胺与2剂量利妥昔单抗和4周糖皮质激素的组合是优选的治疗方法。该结果将指导研究最少使用糖皮质激素治疗AAV的试验的发展。
UNASSIGNED: Research in anti-neutrophil cytoplasmic antibody-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 should accept as the lowest
glucocorticoid dosing that can be used in induction therapy for AAV.
UNASSIGNED: International, online survey.
UNASSIGNED: Clinicians in various countries with experience in managing vasculitis.
UNASSIGNED: Survey 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 3 candidate trial designs, 2 of which proposed a combination of cyclophosphamide and rituximab induction.
UNASSIGNED: Using a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen would be safe and effective and their willingness to randomize into the trial.
UNASSIGNED: There 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-week
glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4-week glucocorticoids was the most preferred design. Forty-two percent of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients.
UNASSIGNED: Representativeness of survey sample and generalizability of findings.
UNASSIGNED: Combination 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 is important.
Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on using less glucocorticoids to limit side effects. New drugs that drastically limit
glucocorticoid use are not available in many countries. Studies are needed to find other ways of reducing glucocorticoid exposure to treat AAV, but it is unclear how best to achieve this. We administered a survey to doctors with experience in treating AAV and had them grade different combinations of widely available treatments with 2 or 4 weeks of glucocorticoids. We found that a combination of 2 doses cyclophosphamide with 2 doses rituximab and 4 weeks of glucocorticoids was the preferred treatment. The results will guide the development of a trial studying minimal use of glucocorticoids for the treatment of AAV.