Division of Renal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nova South Eastern University, Fort Lauderdale, Florida, USA.
Am J Nephrol. 2019;50(5):386-391. doi: 10.1159/000503318. Epub 2019 Oct 8.
The introduction of combination therapy with glucocorticoids (GC) and cyclophosphamide (CYC) or rituximab (RTX) has resulted in remission rates exceeding 90% in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, early treatment-related mortality remains a major concern and has driven the search for safer induction regimens exploring minimization or avoidance of GC and CYC. Most trials have excluded patients with severe renal disease. We report the outcomes of AAV patients with severe renal disease treated with sequential therapy (ST) starting with (GC) and oral (CYC) followed by transition to (RTX).
Patients with new or relapsing severe AAV who presented with severe renal disease and/or rapidly progressive glomerulonephritis (RPGN) were identified. RPGN was defined as at least a 20% decrease in estimated glomerular filtration rate (eGFR) over a 2-week period along with hematuria and proteinuria. Induction treatment included pulse (GC) for 3 days followed by oral prednisone tapered to 5 mg by month 6, oral (CYC) adjusted for GFR until improvement in Birmingham Vasculitis Activity Score (BVAS), and serum creatinine at which point (CYC) was stopped and induction dose of (RTX) was given. Use of plasmapheresis (PLEX) was allowed. The primary outcome was complete remission defined as BVAS of zero by 6 months. Descriptive data are presented as median with range and mean with SD.
Nine patients met the inclusion criteria. Median age at diagnosis was 63 years. The majority were females, myeloperoxidase ANCA positive, and had a new diagnosis. The mean nadir (SD) eGFR was 12 (5) with 3 requiring dialysis. The median BVAS at the time of diagnosis was 15. All patients received ST and 3 received PLEX. The median exposure to oral CYC was 35 days. The mean (SD) eGFR and median BVAS were 26 (12) and 3, respectively, at the time of switching to RTX. The median prednisone dose at 6M was 5 mg. The median follow-up was 44 months. All patients achieved remission. One patient with relapsing disease reached ESRD. The mean (SD) eGFR in the remaining 8 patients at last FU was 37 (27), and the mean (SD) eGFR rise at 1 year was 26 (25). Adverse events included 2 patients with pneumonia and 3 with bone marrow suppression. There were no deaths.
ST with GC and CYC followed by RTX is effective for in AAV patients with severe renal disease. Therapy-related adverse events are comparable to other studies, and further modification in ST with decrease in GC dosage should be explored.
糖皮质激素（GC）和环磷酰胺（CYC）或利妥昔单抗（RTX）联合治疗的引入，使得抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）患者的缓解率超过 90%。然而，早期治疗相关死亡率仍然是一个主要关注点，并促使人们探索更安全的诱导方案，以尽量减少或避免使用 GC 和 CYC。大多数试验都排除了患有严重肾脏疾病的患者。我们报告了接受序贯治疗（ST）的严重肾脏疾病 AAV 患者的结果，起始治疗为（GC）和口服（CYC），随后转换为（RTX）。
确定了新诊断或复发的严重 AAV 患者，这些患者表现为严重的肾脏疾病和/或快速进展性肾小球肾炎（RPGN）。RPGN 的定义为在 2 周内估计肾小球滤过率（eGFR）下降至少 20%，同时伴有血尿和蛋白尿。诱导治疗包括静脉注射（GC）3 天，随后口服泼尼松，在第 6 个月时减至 5mg，根据肾小球滤过率调整口服（CYC）剂量，直至伯明翰血管炎活动评分（BVAS）改善，且血清肌酐达到该水平时停止（CYC），并给予（RTX）诱导剂量。允许使用血浆置换（PLEX）。主要结局是在 6 个月时定义为 BVAS 为零的完全缓解。描述性数据以中位数（范围）和平均值（标准差）表示。
9 名患者符合纳入标准。中位诊断时年龄为 63 岁。大多数患者为女性，髓过氧化物酶 ANCA 阳性，为新诊断。最低（SD）eGFR 的平均值（SD）为 12（5），有 3 名患者需要透析。诊断时的中位 BVAS 为 15。所有患者均接受 ST 治疗，3 名患者接受 PLEX 治疗。中位口服 CYC 暴露时间为 35 天。转换为 RTX 时的平均（SD）eGFR（SD）和中位 BVAS 分别为 26（12）和 3。6 个月时的中位泼尼松剂量为 5mg。中位随访时间为 44 个月。所有患者均达到缓解。1 例复发疾病患者进展至终末期肾病。其余 8 例患者在最后一次随访时的平均（SD）eGFR 为 37（27），1 年时 eGFR 的平均（SD）升高为 26（25）。不良事件包括 2 例肺炎和 3 例骨髓抑制。无死亡。
GC 和 CYC 序贯治疗后再用 RTX 治疗严重肾脏疾病的 AAV 患者是有效的。治疗相关的不良反应与其他研究相似，应进一步探索减少 GC 剂量的 ST 治疗方案。
