Kachaner Alexandra, Mageau Arthur, Goulenok Tiphaine, François Chrystelle, Delory Nicole, Chauveheid Marie-Paule, Laouenan Cedric, Doan Serge, Halimi Caroline, Klein Isabelle, Papo Thomas, Sacré Karim
Department of Internal Medicine, Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
Department of Epidemiology, Biostatistics and Clinical Research, Hôpital Bichat-Claude Bernard, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France.
Lancet Rheumatol. 2025 Jan;7(1):e15-e20. doi: 10.1016/S2665-9913(24)00220-0. Epub 2024 Sep 18.
Susac syndrome is a rare disease affecting mainly young women and is characterised by an occlusive microvessel disease limited to the brain, retina, and inner ear. No randomised controlled trial has been published or declared as ongoing to investigate treatments for Susac syndrome. We aimed to compare the effect of glucocorticoids given alone or in combination with immunosuppressive agents or intravenous immunoglobulin for the prevention of relapse in patients with Susac syndrome.
The Phenotypic and Etiological Characterization of Susac Syndrome-National Clinical Research Hospital Program study is a prospective national cohort study that started enrolling on Nov 29, 2011, and included all consecutive patients aged 18 years or older with Susac syndrome who were referred to the French reference centre (Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris). Susac syndrome was defined by either the triad of encephalopathy with typical brain MRI abnormalities, cochleo-vestibular damage, and multiple occlusions of retinal central artery branches, or at least two of the three criteria without any alternative diagnosis. Collected data included fundoscopy, retinal angiography, audiometry, cerebrospinal fluid, brain MRI, and treatment received at diagnosis; months 1, 3, 6, and 12 after diagnosis; and then annually for 5 years or in the case of a relapse. The primary outcome was defined as the first relapse occurring within a 36-month follow-up period from the first day of treatment, characterised by new clinical symptoms or signs, and new abnormalities observed on retinal angiography, audiometry, or brain MRI, necessitating treatment intensification. There was no involvement of people with lived experience at any stage. The study is registered at ClinicalTrials.gov, NCT01481662.
Between Nov 29, 2011, and Dec 2, 2022, 64 patients were included in the study, with a mean age at diagnosis of 35 years (SD 11); 41 (64%) were women and 23 (36%) were men. At diagnosis, 60 patients received glucocorticoids; 40 (63%) of 64 patients received glucocorticoids alone as a first-line therapy while 20 (31%) received glucocorticoids in combination with immunosuppressive agents or intravenous immunoglobulin. Overall, 46 (72%) of 64 patients had a first relapse with a median relapse-free survival time of 3·96 months (95% CI 2·24-16·07). Comparison of relapse-free survival showed no significant difference between the two treatment strategies (hazard ratio [HR] 1·11 [95% CI 0·56-2·17], p=0·76), compared with glucocorticoids alone as the reference group. In patients who first relapsed while treated with glucocorticoids alone, there was no significant difference in second relapse-free survival between those who did or did not receive immunosuppressive agents or intravenous immunoglobulin as a second-line therapy (HR 2·66 [95% CI 0·63-11·18], p=0·18).
The combination of glucocorticoids with immunosuppressive agents or intravenous immunoglobulin did not appear to reduce the risk of Susac syndrome relapse compared with glucocorticoids alone. Our findings did not support the systematic use of immunosuppressive agents in Susac syndrome.
French Ministry of Health.
Susac综合征是一种罕见疾病，主要影响年轻女性，其特征为局限于脑、视网膜和内耳的闭塞性微血管疾病。尚无已发表或正在进行的随机对照试验来研究Susac综合征的治疗方法。我们旨在比较单独使用糖皮质激素或联合免疫抑制剂或静脉注射免疫球蛋白预防Susac综合征患者复发的效果。
Susac综合征的表型和病因特征——国家临床研究医院项目研究是一项前瞻性全国队列研究，于2011年11月29日开始招募，纳入了所有连续转诊至法国参考中心（巴黎比夏-克劳德·贝尔纳医院内科）的18岁及以上Susac综合征患者。Susac综合征的定义为脑病三联征伴典型脑MRI异常、耳蜗前庭损害以及视网膜中央动脉分支多处闭塞，或三项标准中的至少两项且无其他替代诊断。收集的数据包括眼底镜检查、视网膜血管造影、听力测定、脑脊液、脑MRI以及诊断时、诊断后1个月、3个月、6个月和12个月接受的治疗；之后每年收集5年或直至复发的数据。主要结局定义为从治疗第一天起36个月随访期内首次复发，其特征为出现新的临床症状或体征，以及视网膜血管造影、听力测定或脑MRI上出现新的异常，需要强化治疗。在任何阶段都没有患者参与。该研究已在ClinicalTrials.gov注册，注册号为NCT01481662。
在2011年11月29日至2022年12月2日期间，64例患者纳入研究，诊断时的平均年龄为35岁（标准差11）；4位1（64%）为女性，23位1（36%）为男性。诊断时，60例患者接受了糖皮质激素治疗；64例患者中的40例（63%）单独接受糖皮质激素作为一线治疗，而20例（31%）接受糖皮质激素联合免疫抑制剂或静脉注射免疫球蛋白治疗。总体而言，64例患者中的46例（例72%）首次复发，无复发存活时间的中位数为3.96个月（95%置信区间2.24 - 16.07）。与单独使用糖皮质激素作为参照组相比，两种治疗策略的无复发存活情况比较无显著差异（风险比[HR]1.11[95%置信区间0.56 - 2.17]，p = 0.76）。在单独接受糖皮质激素治疗时首次复发的患者中，接受或未接受免疫抑制剂或静脉注射免疫球蛋白作为二线治疗的患者，第二次无复发存活情况无显著差异（HR2.66[95%置信区间0.63 - 11.18]，p =）
与单独使用糖皮质激素相比，糖皮质激素联合免疫抑制剂或静脉注射免疫球蛋白似乎并未降低Susac综合征复发的风险。我们的研究结果不支持在Susac综合征中系统性使用免疫抑制剂。
法国卫生部。
