Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis
Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis
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DOI：
10.1093/rheumatology/keu452
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发表时间：
2015-07-01
期刊：
影响因子：
5.5
通讯作者：
Jayne, David R. W.
中科院分区：
文献类型：
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作者：
Alberici, Federico;Smith, Rona M.;Jayne, David R. W.
客观的。 ANCA 相关性血管炎 (AAV) 的特点是慢性复发病程。利妥昔单抗（RTX）是一种有效的维持治疗；然而，终止后的长期结果尚不清楚。本研究的目的是探讨接受重复剂量 RTX 维持治疗的 AAV 患者的长期结局。方法。接受 RTX 治疗方案（包括诱导期和维持期）的 AAV 患者也被纳入其中。对于初始缓解诱导，RTX 剂量为每 2 周 1 g 或每周 375 mg/m(2)，连续 4 周；为了缓解维持，每 6 个月 1 g，持续 24 个月。在第一次 RTX 给药时，停用正在进行的免疫抑制剂。结果。确定了 69 名患者，其中 67 名其他治疗失败。 9 例在 RTX 治疗方案期间复发；然而，在中位泼尼松龙剂量为 2.5 毫克/天的维持阶段结束时，所有 69 例患者均处于缓解状态，并且 9% 的患者正在接受额外的免疫抑制治疗。在随后的观察中，28 名患者在最后一次 RTX 输注后平均 34.4 个月复发。复发的危险因素包括 PR3 相关疾病 (P = 0.039)、最后一次 RTX 输注后 12 个月内 B 细胞返回 (P = 0.0038) 以及 ANCA 阴性转为阳性 (P = 0.0046)。两名患者死亡，两名患者出现严重的低丙种球蛋白血症。结论。本研究支持固定间隔 RTX 维持方案治疗复发/难治性 AAV 的有效性和安全性。停止维持治疗后确实发生了复发，但复发率低于单次 RTX 诱导疗程后的复发率。 PR3相关疾病、ANCA从阴性转为阳性以及最后一次RTX给药后12个月内B细胞恢复是进一步复发的危险因素。
Objective. ANCA-associated vasculitis (AAV) is characterized by a chronic relapsing course. Rituximab (RTX) is an effective maintenance treatment; however, the long-term outcomes after its discontinuation are unclear. The aim of this study was to explore the long-term outcomes of AAV patients treated with repeat-dose RTX maintenance therapy.Methods. AAV patients receiving a RTX treatment protocol consisting of an induction and maintenance phase were included. For initial remission induction, RTX was dosed at 1 g every 2 weeks or 375 mg/m(2) weekly for 4 consecutive weeks and for remission maintenance at 1 g every 6 months for 24 months. At the first RTX administration, ongoing immunosuppressives were withdrawn.Results. Sixty-nine patients were identified, 67 of whom were failing other therapies. Nine relapsed during the RTX treatment protocol; however, all 69 were in remission at the end of the maintenance phase on a median prednisolone dose of 2.5 mg/day and 9% were receiving additional immunosuppression. During subsequent observation, 28 patients relapsed a median of 34.4 months after the last RTX infusion. Risk factors for relapse were PR3-associated disease (P = 0.039), B cell return within 12 months of the last RTX infusion (P = 0.0038) and switch from ANCA negativity to positivity (P = 0.0046). Two patients died and two developed severe hypogammaglobulinaemia.Conclusion. This study supports the efficacy and safety of a fixed-interval RTX maintenance regimen in relapsing/refractory AAV. Relapses after discontinuation of maintenance therapy did occur, but at a lower rate than after a single RTX induction course. PR3-associated disease, the switch from ANCA negative to positive and the return of B cells within 12 months of the last RTX administration were risk factors for further relapse.