National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 Chome-1-1 Ogawahigashicho, Kodaira, Tokyo 187-8551, Japan.
Department of Neurology, Kawakita General Hospital, 1-7-3 Asagayakita, Suginami, Tokyo 166-8588, Japan.
Mult Scler Relat Disord. 2022 May;61:103772. doi: 10.1016/j.msard.2022.103772. Epub 2022 Mar 25.
Neuromyelitis optica spectrum disorder (NMOSD) is a rare, chronic, autoimmune disease, characterized by astrocytopathic lesions in the central nervous system (Beekman et al., 2019; Fujihara et al., 2020). The main aim of NMOSD maintenance therapy is to reduce the frequency and severity of relapses and minimize future disability (Fujihara et al., 2020). Oral corticosteroids are used long-term to prevent relapses, but are associated with serious complications (Kessler et al., 2016; Kimbrough et al., 2012). In the SAkuraSky study, satralizumab reduced the risk of relapse in patients with NMOSD compared with placebo, with comparable rates of serious adverse events and infections between treatment arms (Yamamura et al., 2019). Here, we report on 16 patients who tapered their steroid dose during the openlabel extension (OLE) period of SAkuraSky.
SAkuraSky was a phase 3, multicenter, randomized, double-blind (DB), placebo-controlled study of satralizumab in combination with immunosuppressive therapies (ISTs) in patients with NMOSD. Patients were randomized 1:1 to receive 120 mg subcutaneous satralizumab or placebo in addition to a stable dose of their baseline IST. After completing the DB period or experiencing relapse, patients could enter the OLE period. In the OLE, all patients received satralizumab, and IST doses could be tapered at the investigator's discretion. We assessed the different steroid tapering patterns and their impact on relapse and safety. Patients were considered to have tapered their steroids if their steroid dose at the clinical cut-off date (CCOD: February 18, 2020) was lower than on the first day of the OLE. Annualized relapse rate (ARR) was calculated as the number of relapses divided by the total number of patientyears at risk.
Overall, 36 patients receiving oral corticosteroids entered the OLE, of whom 16 tapered their steroid dose. The mean age (range) at baseline was 44.9 (16-73) years, all 16 were female, 14 (88%) were Japanese, and 15 (94%) were AQP4-IgG seropositive. None were receiving any additional ISTs. Patients tapered their steroids from a median of 10 (range: 5-25) mg/day at OLE baseline to 2.75 (0-15) mg/day at the CCOD. Three patients discontinued steroids entirely, and all three remained relapse free. One patient who remained relapse free had temporary increases in steroid dose. Three relapses were observed in two patients who tapered steroids during the OLE; all three relapses required treatment. One of the relapses occurred shortly after a drop in steroid dose from 25 to 10 mg/day. The ARR for steroid-tapered patients was numerically lower in the OLE period than the satralizumab group in the DB period. The safety profile of satralizumab was in line with the overall SAkuraSky population. Two serious infections were observed in steroid-tapered patients in the OLE, both in the same patient: one event (hepatitis E) occurred before the patient began tapering their steroid dose; and one event (influenza) occurred while the patient was tapering.
During the OLE of SAkuraSky, 16 patients tapered steroids and the ARR did not increase from the DB period. Patient numbers limit interpretation.
视神经脊髓炎谱系疾病（NMOSD）是一种罕见的、慢性的自身免疫性疾病，其特征是中枢神经系统（CNS）的星形胶质细胞病变（Beekman 等人，2019 年；Fujihara 等人，2020 年）。NMOSD 维持治疗的主要目的是减少复发的频率和严重程度，并最大限度地减少未来的残疾（Fujihara 等人，2020 年）。长期使用口服皮质类固醇预防复发，但会引起严重的并发症（Kessler 等人，2016 年；Kimbrough 等人，2012 年）。在 SakuraSky 研究中，与安慰剂相比，satralizumab 降低了 NMOSD 患者的复发风险，治疗组之间严重不良事件和感染的发生率相当（Yamamura 等人，2019 年）。在这里，我们报告了在 SakuraSky 的开放标签扩展（OLE）期间，16 名患者减少了他们的类固醇剂量。
SakuraSky 是一项 3 期、多中心、随机、双盲（DB）、安慰剂对照的 satralizumab 联合免疫抑制疗法（ISTs）治疗 NMOSD 的研究。患者按 1:1 随机接受 120mg 皮下 satralizumab 或安慰剂，同时使用其基线 IST 的稳定剂量。完成 DB 期或发生复发后，患者可以进入 OLE 期。在 OLE 中，所有患者均接受 satralizumab 治疗，研究者可以自行调整 IST 剂量。我们评估了不同的类固醇减量模式及其对复发和安全性的影响。如果患者在临床截止日期（CCOD：2020 年 2 月 18 日）的类固醇剂量低于 OLE 开始时的剂量，则认为患者已经开始减少类固醇剂量。年复发率（ARR）的计算方法为复发次数除以风险患者总人数。
总体而言，36 名接受口服皮质类固醇治疗的患者进入 OLE，其中 16 名患者减少了他们的类固醇剂量。基线时的平均年龄（范围）为 44.9（16-73）岁，所有患者均为女性，14 名（88%）为日本人，15 名（94%）为 AQP4-IgG 血清阳性。没有患者接受任何额外的 IST。患者从 OLE 基线时的中位数 10（范围：5-25）mg/天开始逐渐减少类固醇剂量，至 CCOD 时的 2.75（0-15）mg/天。3 名患者完全停止使用类固醇，且这 3 名患者均未复发。1 名仍未复发的患者暂时增加了类固醇剂量。在 OLE 期间，2 名患者中有 3 名患者出现了类固醇减量的复发；所有 3 例复发均需要治疗。其中 1 例复发发生在类固醇剂量从 25mg/天降至 10mg/天之后不久。OLE 期间类固醇减量患者的 ARR 低于 DB 期间 satralizumab 组。SakuraSky 总体人群中，satralizumab 的安全性与预期一致。在 OLE 期间，2 名类固醇减量患者出现 2 例严重感染，均发生在同一名患者中：1 例（戊型肝炎）发生在患者开始减少类固醇剂量之前；1 例（流感）发生在患者减量期间。
在 SakuraSky 的 OLE 期间，16 名患者减少了类固醇剂量，且 ARR 没有高于 DB 期。由于患者人数有限，因此无法进行解释。
