From the Department of Neurology (J.Y., M.C.D.), Thomas Jefferson University, Philadelphia, PA; and National and Kapodistrian University of Athens (M.C.D.).
From the Department of Neurology (J.Y., M.C.D.), Thomas Jefferson University, Philadelphia, PA; and National and Kapodistrian University of Athens (M.C.D.). marinos.dalakas@jefferson
Neurol Neuroimmunol Neuroinflamm. 2022 Jul 7;9(5). doi: 10.1212/NXI.0000000000200011. Print 2022 Sep.
IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years.
Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance IVIg by the same neurologists, were analyzed. Response was assessed by physician-observed changes, patients' reports of symptom improvement, modified Rankin Scale (mRS) scores, and dependency trials evaluating symptom recurrence after stopping IVIg, prolonging infusion frequency, decreasing monthly dose, or wearing-off effects in between doses. Clinically meaningful long-term response was defined by improved mRS scores, improvement in physician-assessed stiffness, balance and gait, and functional decline with dependency trials.
Twenty-four of 36 (67%) patients had clinically meaningful response over a median 40-month period. Patients with improved mRS scores by 1-2 points manifested improved gait, posture, balance and decreased stiffness, spasms, and startle response; some patients using a wheelchair and those ambulating with devices walked unassisted. In 25% of responders, treatment benefit was sustained for a 40-month median period, but in 29.1%, it declined over a 39-month period; 12.5% exhibited a conditioning effect. Three of 5 patients with cerebellar GAD-SPS variant also improved over time. The 12 patients who did not respond the first 3 months remained unresponsive even if IVIg continued for several months.
This is a large study in 36 patients with SPS demonstrating that monthly maintenance IVIg therapy offers long-term benefits in 67% of patients for a median 3.3-year period. Because 29.1% experienced diminishing benefit over time due to disease progression, the study highlights the need for more effective therapies.
基于一项为期 3 个月的对照试验，静脉注射免疫球蛋白（IVIg）已成为僵硬人综合征（SPS）的首选免疫疗法，但它是否也能带来长期益处或阻止疾病进展尚不清楚。由于 SPS 是一种进行性致残疾病，IVIg 作为慢性治疗药物广泛应用，但缺乏疗效数据，因此需要了解相关信息。本研究探索了在同一位临床医生 10 年以上时间内对最大队列的、特征明确的 SPS 患者进行 IVIg 长期治疗的效果。
分析了 36 名患者（32 名谷氨酸脱羧酶 [GAD] 阳性）的数据，这些患者由同一位神经科医生每月进行维持性 IVIg 治疗。通过医生观察到的变化、患者报告的症状改善、改良 Rankin 量表（mRS）评分、以及停止 IVIg 输注、延长输注频率、减少每月剂量或剂量之间出现失效效应后评估症状复发的依赖性试验来评估反应。临床意义上的长期反应定义为 mRS 评分改善、医生评估的僵硬、平衡和步态改善以及依赖性试验中的功能下降。
在中位数为 40 个月的时间内，36 名患者中有 24 名（67%）患者具有临床意义的反应。mRS 评分改善 1-2 分的患者表现出步态、姿势、平衡改善，僵硬、痉挛和惊跳反应减少；一些患者使用轮椅，一些使用助行器的患者可独立行走。在 25%的反应者中，治疗益处持续了中位数 40 个月，但在 29.1%的患者中，治疗益处持续了 39 个月；12.5%的患者出现了条件作用。3 名小脑 GAD-SPS 变异患者也随时间改善。前 3 个月未反应的 12 名患者即使继续 IVIg 治疗几个月也仍无反应。
这是一项对 36 名 SPS 患者进行的大型研究，表明每月维持性 IVIg 治疗可在中位数 3.3 年的时间内为 67%的患者带来长期益处。由于 29.1%的患者由于疾病进展而导致治疗益处逐渐减少，因此该研究强调需要更有效的治疗方法。
