Background:Evobrutinib – an oral, central nervous system (CNS)-penetrant, and highly selective Bruton’s tyrosine kinase inhibitor – has shown efficacy in a 48-week, double-blind, Phase II trial in patients with relapsing MS.Objective:Report results of the Phase II open-label extension (OLE; up to week 192 from randomisation) and a cerebrospinal fluid (CSF) sub-study.Methods:In the 48-week double-blind period (DBP), patients received evobrutinib 25 mg once-daily, 75 mg once-daily, 75 mg twice-daily or placebo (switched to evobrutinib 25 mg once-daily after week 24). Patients could then enter the OLE, receiving evobrutinib 75 mg once-daily (mean (± standard deviation (SD)) duration = 50.6 weeks (±6.0)) before switching to 75 mg twice-daily.Results:Of 164 evobrutinib-treated patients who entered the OLE, 128 (78.0%) completed ⩾192 weeks of treatment. Patients receiving DBP evobrutinib 75 mg twice-daily: annualised relapse rate at week 48 (0.11 (95% confidence interval (CI) = 0.04-0.25)) was maintained with the OLE twice-daily dose up to week 192 (0.11 (0.05–0.22)); Expanded Disability Status Scale score remained stable; serum neurofilament light chain fell to levels like a non-MS population ( Z-scores); T1 gadolinium-enhancing lesion numbers remained low. No new safety signals were identified. In the OLE, evobrutinib was detected in the CSF of all sub-study patients.Conclusion:Long-term evobrutinib treatment was well tolerated and associated with a sustained low level of disease activity. Evobrutinib was present in CSF at concentrations similar to plasma.

中文翻译：

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使用布鲁顿酪氨酸激酶抑制剂 evobrutinib 治疗复发性多发性硬化症超过 3.5 年后的疗效和安全性结果：脑脊液子研究 II 期随机临床试验的长期随访

背景：Evobrutinib – 一种口服、中枢神经系统 (CNS) 渗透性、高选择性布鲁顿氏酪氨酸激酶抑制剂 – 在针对复发性多发性硬化症患者的一项为期 48 周的双盲 II 期试验中显示出疗效。 目的：报告结果II 期开放标签扩展（OLE；随机分组至第 192 周）和脑脊液 (CSF) 子研究。方法：在 48 周双盲期 (DBP) 中，患者接受一次 25 mg evobrutinib -每日、75 mg 每日一次、75 mg 每日两次或安慰剂（第 24 周后改用 evobrutinib 25 mg 每日一次）。然后，患者可以进入 OLE，接受 evobrutinib 75 mg 每日一次（平均（±标准差 (SD)）持续时间 = 50.6 周 (±6.0)），然后改用 75 mg 每日两次。结果：在 164 名接受 evobrutinib 治疗的患者中进入 OLE 的患者中，128 名 (78.0%) 完成了⩾192 周的治疗。接受 DBP evobrutinib 75 mg 每日两次的患者：使用每日两次 OLE 剂量直至第 192 周，第 48 周的年化复发率 (0.11 (95% 置信区间 (CI) = 0.04-0.25)) 保持不变 (0.11 (0.05– 0.22））；扩展残疾状况量表评分保持稳定；血清神经丝轻链下降至非 MS 人群的水平（Z 分数）；T1 钆增强病变数量仍然很低。没有发现新的安全信号。在 OLE 中，所有亚组研究患者的脑脊液中均检测到了 evobrutinib。结论：长期 evobrutinib 治疗耐受性良好，并且与持续的低水平疾病活动相关。Evobrutinib 在脑脊液中的浓度与血浆相似。