Williams Mitzi J, Amezcua Lilyana, Cohan Stanley L, Cohen Jeffrey A, Delgado Silvia R, Hua Le H, Lucassen Elisabeth B, Piccolo Rebecca S, Koulouris Chloe R, Stankiewicz James
From the Joi Life Wellness MS Center (M.J.W.), Atlanta, GA; University of Southern California (L.A.), Los Angeles; Providence Multiple Sclerosis Center (S.L.C.), Providence Brain and Spine Institute, Portland, OR; Cleveland Clinic Mellen Center (J.A.C.) OH; Department of Neurology (S.R.D.), University of Miami Miller School of Medicine, FL; Cleveland Clinic Lou Ruvo Center for Brain Health (L.H.H.), Las Vegas, NV; Novartis Pharmaceuticals Corporation (E.B.L., R.S.P., J.S.), East Hanover, NJ; and Envision Pharma, Inc. (C.R.K.), Horsham, United Kingdom.
Neurology. 2024 Aug 13;103(3):e209610. doi: 10.1212/WNL.0000000000209610. Epub 2024 Jul 17.
Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup.
ASCLEPIOS I/II were identical, double-blind, double-dummy, active-controlled, multicenter, phase 3 trials. Participants were randomized (1:1) to receive ofatumumab 20 mg every 4 weeks or teriflunomide 14 mg once daily for up to 30 months. Pooled data were used to determine the efficacy/safety of ofatumumab vs teriflunomide in participants who self-identified as non-Hispanic Black, non-Hispanic Asian, Hispanic/Latino, or non-Hispanic White. Participants who did not self-identify into one of these groups were classified as other/unknown.
Of the 1,882 participants, 64 (3.4%) self-identified as non-Hispanic Black, 71 (3.8%) as non-Hispanic Asian, 145 (7.7%) as Hispanic/Latino, and 1,538 (81.7%) as non-Hispanic White. Baseline participant demographics/characteristics were largely balanced across subgroups, aside from minor variations in sex, disease duration, and MRI lesions. From months 0 to 24, the proportion of ofatumumab vs teriflunomide-treated patients achieving NEDA-3 (odds ratio [95% CI]) was as follows: non-Hispanic Black, 33.3% vs 3.4% (15.9 [1.67-151.71; = 0.0162]); non-Hispanic Asian, 42.9% vs 21.9% (3.18 [0.95-10.59; = 0.06]); Hispanic/Latino, 36.6% vs 18.6% (3.21 [1.32-7.79; = 0.01]); and non-Hispanic White, 37.4% vs 16.6% (3.57 [2.73-4.67; < 0.0001]). Rates of AEs were generally similar between treatment groups and across race/ethnicity subgroups; no new or unexpected safety signals were identified.
Ofatumumab was associated with greater proportions of NEDA-3 achievement than teriflunomide across race/ethnicity subgroups in the ASCLEPIOS trials. Within each treatment group, the proportion of patients achieving NEDA-3 from months 0 to 24 was similar across the subgroups and overall pooled population. Both ofatumumab and teriflunomide were well tolerated. Future MS trials should include ethnically diverse groups to better inform treatment decisions and improve real-world patient outcomes.
ClinicalTrials.gov: NCT02792218 (clinicaltrials.gov/ct2/show/NCT02792218), NCT02792231 (clinicaltrials.gov/ct2/show/NCT02792231). Submission date: June 2, 2016. First enrollment: August 26, 2016.
This study provides Class II evidence that among patients aged 18-55 years with RMS, the improvement in NEDA-3 with ofatumumab was comparably better than with teriflunomide among patients self-identified as non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, Hispanic/Latino, and other/unknown.
种族和族裔可能会影响多发性硬化症（MS）患者疾病修饰疗法的疗效。不同种族群体中MS的发病率可能更高；然而，这些人群在MS试验中的代表性不足。这项事后分析比较了在ASCLEPIOS I/II试验中入组的复发型MS（RMS）参与者中，按种族/族裔亚组划分的使用奥法妥木单抗与特立氟胺达到三参数无疾病活动证据（NEDA-3）的患者比例。
ASCLEPIOS I/II是相同的、双盲、双模拟、活性对照、多中心3期试验。参与者被随机分配（1:1）接受每4周一次20mg奥法妥木单抗或每日一次14mg特立氟胺，最长30个月。汇总数据用于确定在自我认定为非西班牙裔黑人、非西班牙裔亚洲人、西班牙裔/拉丁裔或非西班牙裔白人的参与者中，奥法妥木单抗与特立氟胺的疗效/安全性。未自我认定为这些群体之一的参与者被归类为其他/未知。
在1882名参与者中，64名（3.4%）自我认定为非西班牙裔黑人，71名（3.8%）为非西班牙裔亚洲人，145名（7.7%）为西班牙裔/拉丁裔，1538名（81.7%）为非西班牙裔白人。除了在性别、疾病持续时间和MRI病变方面的微小差异外，各亚组的基线参与者人口统计学/特征在很大程度上是平衡的。从第0个月到第24个月，奥法妥木单抗与特立氟胺治疗的患者达到NEDA-3的比例（优势比[95%CI]）如下：非西班牙裔黑人，33.3%对3.4%（15.9[1.67 - 151.71]；P = 0.0162）；非西班牙裔亚洲人，42.9%对21.9%（3.18[0.95 - 10.59]；P = 0.06）；西班牙裔/拉丁裔，36.6%对18.6%（3.21[1.32 - 7.79]；P = 0.01）；非西班牙裔白人，37.4%对16.6%（3.57[2.73 - 4.67]；P < 0.0001）。各治疗组之间以及各种族/族裔亚组之间的不良事件发生率总体相似；未发现新的或意外的安全信号。
在ASCLEPIOS试验中，在各种族/族裔亚组中，奥法妥木单抗达到NEDA-3的比例高于特立氟胺。在每个治疗组中，从第0个月到第24个月达到NEDA-3的患者比例在各亚组和总体汇总人群中相似。奥法妥木单抗和特立氟胺的耐受性均良好。未来的MS试验应纳入不同种族群体，以更好地为治疗决策提供信息并改善实际患者的治疗效果。
ClinicalTrials.gov：NCT02792218（clinicaltrials.gov/ct2/show/NCT02792218），NCT02792231（clinicaltrials.gov/ct2/show/NCT02792231）。提交日期：2016年6月2日。首次入组：2016年8月26日。
本研究提供了II类证据，即在18 - 55岁的RMS患者中，在自我认定为非西班牙裔黑人、非西班牙裔亚洲人、非西班牙裔白人、西班牙裔/拉丁裔和其他/未知的患者中，奥法妥木单抗在NEDA-3方面的改善比特立氟胺更好。
