人T细胞白血病病毒1型（HTLV-1）的携带者中，HTLV-1相关髓病/热带痉挛性截瘫病（HAM/TSP）的发病率较高。HTLV-1主要感染CD4+ T细胞，导致终身感染。HAM/TSP当前的治疗方法效果不佳，存在长期副作用问题。本研究评估了抗CCR4抗体摩加木单抗在HAM/TSP患者中的长期安全性和疗效，研究历时4年。我们进行了一项开放标签、长期扩展的研究（UMIN试验编号：UMIN000019942），研究患者为具有肾上腺皮质激素耐药的HAM/TSP患者，能够带助行器行走10米。摩加木单抗以0.01、0.03、0.1或0.3mg/kg剂量间隔≥8周（0.01和0.03mg/kg）或≥12周（0.1和0.3mg/kg）给予。采用描绘性统计方法总结HTLV-1基因组负荷、脑脊液炎性标志物和临床症状。使用末次观察延续法填补缺失观测。作为事后分析，我们通过与HAM/TSP患者登记处的对照数据比较，评估了摩加木单抗对步态功能的治疗效果。在Phase 1-2a试验的21名参与者中，有18名（86%）参加了长期研究，15名（71%）连续剂量予以摩加木单抗治疗4年。4年后，中位剂量为0.1mg/kg。21名参与者中，有17名（81%）经历1-2级皮肤相关的不良事件。观察到3例淋巴细胞减少症和各1例小血管炎、门冬氨酸转移酶水平升高和中性粒细胞减少症。21名参与者中有4人（19%）产生中和抗体。4年后，外周血基因组负荷和脑脊液感染细胞数分别降低了60.7%和66.3%。神经酰胺和CXCL10脑脊液浓度分别降低了37.0%和31.0%。在18名参与者中，17人（94%）的痉挛和Osame运动障碍评分得分有所改善，4人（22%）的Osame运动障碍评分得分有所改善。然而，10米步行时间平均恶化了7.3%。与现代对照组的比较表明，摩加木单抗能抑制Osame运动障碍评分得分的进展（p = 0.02）。研究结果表明，摩加木单抗在肾上腺皮质激素治疗的HAM/TSP患者中具有长期安全性和抑制下肢运动障碍进展的功效，为将摩加木单抗应用于HAM/TSP治疗提供了依据。© 2023作者。由牛津大学出版社代表Brain的保证人保留所有权利。要获取权限，请发送电子邮件至：journals.permissions@oup.com。

Some carriers of human T-cell leukemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a Phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1, or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, cerebrospinal fluid inflammatory markers, and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post-hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the Phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and 4 (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (p = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effect on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment.© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.