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在资源有限的情况下,对严重慢性难治性重症肌无力患者进行单次低剂量利妥昔单抗输注。

A single low-dose rituximab infusion in severe chronic refractory myasthenia gravis in resource-limited settings.

机构信息

Neurology Division, Department of Medicine, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa.

出版信息

J Neurol Sci. 2022 Nov 15;442:120394. doi: 10.1016/j.jns.2022.120394. Epub 2022 Aug 30.

Abstract

The benefits of multi-dose rituximab cycles in patients with refractory anti-muscle-specific kinase antibody myasthenia gravis (MuSK+MG) are well reported, although less consistently in anti-acetylcholine receptor antibody MG (AChR+MG). Responsivity data to single low-dose rituximab infusions for refractory autoimmune myasthenia, are limited. Here, observational outcomes using MG grading scores and prednisone doses, before and after at least six months of a single-dose infusion of rituximab, were audited in previously treatment-refractory MG patients in a resource-limited setting. Seventeen moderately-severe to severely symptomatic MG patients received single low-dose rituximab infusions (median 500-600 mg) after a median MG duration of 6 years; 13 individuals responded including 5/5 MuSK+MG, 7/10 AChR+MG and 1/2 double seronegative MG. Three (60%) MuSK+MG and three (30%) AChR+MG achieved persistent asymptomatic status. Although more MuSK+MG vs AChR+MG cases stopped prednisone (80% vs 20%, respectively), the prednisone doses in the AChR+MG group was significantly reduced ≥30% (p = 0.008) due to improved MG composite scores (p = 0.016) and with durable benefit (median 12 months). There were no differences between responders and non-responders in MG duration and age at infusion. These results suggest that a single low-dose rituximab infusion is worth trying in refractory MG, including AChR+MG patients, as some patients showed good and durable responses. These results are particularly relevant to resource-limited settings.

摘要

多剂量利妥昔单抗治疗方案在难治性抗肌肉特异性激酶抗体型重症肌无力(MuSK+MG)患者中效果显著,然而在乙酰胆碱受体抗体型重症肌无力(AChR+MG)患者中效果并不稳定。对于难治性自身免疫性重症肌无力患者,单次低剂量利妥昔单抗输注的应答数据有限。在资源有限的环境下,我们观察了先前治疗无效的重症肌无力患者在接受至少 6 个月单次剂量利妥昔单抗输注后的 MG 分级评分和泼尼松剂量变化。17 例中重度症状性重症肌无力患者接受了单次低剂量利妥昔单抗输注(中位数 500-600mg),中位 MG 病程为 6 年;13 例患者有应答,包括 5/5 MuSK+MG、7/10 AChR+MG 和 1/2 双重血清阴性 MG。3 例(60%)MuSK+MG 和 3 例(30%)AChR+MG 达到持续无症状状态。尽管 MuSK+MG 组中有更多病例停用泼尼松(80%比 20%),但 AChR+MG 组的泼尼松剂量显著减少≥30%(p=0.008),这与 MG 综合评分改善(p=0.016)和持久获益相关(中位数 12 个月)。应答者和无应答者在 MG 病程和输注时年龄方面无差异。这些结果表明,对于难治性重症肌无力患者,包括 AChR+MG 患者,单次低剂量利妥昔单抗输注是值得尝试的,因为一些患者表现出良好和持久的反应。这些结果对于资源有限的环境特别相关。

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