Five Years of Ublituximab in Multiple Sclerosis: ULTIMATE I and II Open-Label Extension Study.

Background

To evaluate long-term ublituximab clinical efficacy and safety.

评估长期ublituximab的临床疗效和安全性。

DESIGN, SETTING, AND PARTICIPANTS: The 2-year, multicenter, randomized, active-controlled, double-blindperiod (DBP) of the ULTIMATE I and II phase 3 studies occurred September 2017 to November 2020.

设计、设置和参与者：ULTIMATE I和II第三阶段研究的2年期、多中心、随机、活性对照、双盲期（DBP）发生在2017年9月至2020年11月。

Enrollment in the ongoing ULTIMATE open-label extension (OLE) study began November 2019; data cutoff for this analysis was January 1, 2024.

ULTIMATE开放标签扩展（OLE）研究的招募始于2019年11月；本次分析的数据截止日期为2024年1月1日。

intervention

ULTIMATE OLE participants continued ublituximab (UBL-UBL) or switched from teriflunomide to ublituximab (TER-UBL).

ULTIMATE OLE参与者继续使用ublituximab (UBL-UBL) 或者从特立氟胺切换到ublituximab (TER-UBL)。

main_outcomes_and_measures

Efficacy (annualized relapse rate [ARR], 24-week confirmed disability progression [CDP24], and 24-week confirmed disability improvement [CDI24]) and safety were key outcomes.

疗效（年化复发率[ARR]，24周确认的残疾进展[CDP24]，和24周确认的残疾改善[CDI24]）和安全性是关键结果。

Results

Of 985 adults with RMS who completed ULTIMATE I and II, 851 enrolled in the ULTIMATE OLE and were included in the analysis.

在完成ULTIMATE I和II的985名成人RMS患者中，有851名参与了ULTIMATE OLE并被纳入分析。

On DBP completion, more than 85% of participants (UBL-UBL, 422 of 494; TER-UBL, 429 of 491) entered the OLE, of whom more than 70% (UBL-UBL, 297 of 422; TER-UBL, 327 of 429) continued taking ublituximab at year 5 (OLE year 3) at data cutoff, making up the analysis population (mean [SD] age, 38.5 [9.7] years; 532 female [62.5%]).

在完成DBP后，超过85%的参与者（UBL-UBL，494人中有422人；TER-UBL，491人中有429人）进入了OLE，其中超过70%（UBL-UBL，422人中有297人；TER-UBL，429人中有327人）在数据截止时继续在第5年（OLE第3年）服用ublituximab，构成了分析人群（平均[标准差]年龄，38.5[9.7]岁；532名女性[62.5%]）。

TER-UBL participants experienced a 58.4% ARR reduction at 1 year after the switch (0.182 vs 0.076; rate ratio, 0.42; 95% CI, 0.29-0.60; P < .001), and ARR continued to decrease to 0.048 (year 4) and 0.045 (year 5).

TER-UBL 参与者在转换后 1 年的年复发率（ARR）降低了 58.4%（0.182 对比 0.076；比率比，0.42；95% 置信区间，0.29-0.60；P < .001），并且 ARR 继续下降至第 4 年的 0.048 和第 5 年的 0.045。

UBL-UBL participants had further ARR reductions after the DBP (0.053, 0.032, and 0.020 for years 3, 4, and 5, respectively).

UBL-UBL 参与者在双盲期（DBP）后 ARR 进一步降低（第 3 年为 0.053，第 4 年为 0.032，第 5 年为 0.020）。

At year 5, CDP24 was 8.0% in UBL-UBL participants vs 14.3% in TER-UBL participants (P = .01), and CDI24 was 17.0% in UBL-UBL participants vs 12.2% in TER-UBL participants (P = .02).

在第5年时，UBL-UBL参与者中的CDP24为8.0%，而TER-UBL参与者为14.3%（P = .01），同时UBL-UBL参与者中的CDI24为17.0%，而TER-UBL参与者为12.2%（P = .02）。

Adverse events were consistent with the established safety profile from pivotal trials, with exposure-adjusted incidencerates per 100 participant-years of serious infections (excluding COVID events) of 2.10 (UBL-UBL) and 2.58 (TER-UBL).

不良事件与关键试验中确立的安全性档案一致，每100参与者年中严重感染（排除COVID事件）的暴露调整发生率为2.10（UBL-UBL）和2.58（TER-UBL）。

On average, immunoglobulin levels remained above the lower limit of normal, and no significant differences in serious infection rates were observed regardless of immunoglobulin level.

平均而言，免疫球蛋白水平保持在正常范围的下限以上，且无论免疫球蛋白水平如何，严重感染率均未见显著差异。

conclusions_and_relevance

Results reveal that sustained clinical benefits were observed with 5 years of ublituximab treatment: ARR in year 5 showed 1 relapse per 50 participant-years of ublituximab treatment and 92% of UBL-UBL participants remained free from CDP24.

研究结果表明，在接受5年ublituximab治疗后，观察到持续的临床益处：第5年的累积复发率显示每50名参与者中有1次复发，且92%的UBL-UBL参与者在24周内保持无残疾进展。

Results confirm long-term ublituximab benefits and early initiation of high-efficacy treatment.

研究结果证实了长期使用ublituximab的好处以及早期开始高效治疗的重要性。

trial_registration

ClinicalTrials.gov Identifier: NCT04130997.

ClinicalTrials.gov注册号：NCT04130997。