McGill University Health Centre, Montreal, Quebec, Canada.
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Mol Genet Metab. 2022 Sep-Oct;137(1-2):164-172. doi: 10.1016/j.ymgme.2022.08.007. Epub 2022 Aug 30.
The Morquio A Registry Study (MARS) is an ongoing, multinational, observational study of patients with MPS IVA. Key objectives of MARS are to characterize the heterogeneity and natural history of disease and to evaluate long-term effectiveness and safety of elosulfase alfa enzyme replacement therapy (ERT). Enrollment began in September 2014; data on medical history, clinical outcomes, and safety assessments are collected as part of routine care.
As of February 2021, 381 subjects from 17 countries had enrolled in MARS: 58 ERT-naïve subjects and 323 ERT-treated subjects (≥1 infusion), with a mean ERT exposure of 5.5 years (SD 2.8) and median age at first ERT treatment of 9.8 years. ERT-treated subjects were younger at diagnosis (median 3.4 vs 6.5 years) relative to ERT-naïve subjects. Among ERT-treated subjects, urinary keratan sulfate (uKS) levels declined from pre-ERT baseline to last follow-up on treatment (mean % change [95% confidence interval]: -52.5% [-57.5%, -47.4%]; n = 115) and 6-min walk test distance remained stable (mean change: -6.1 [-27.6, 15.5] m; n = 131) over a mean follow-up of 5.5 years. Forced expiratory volume in 1 s (FEV) and forced vital capacity (FVC) increased in subjects who were < 18 years of age at ERT initiation (mean change: +0.3 [0.1, 0.4] L and + 0.4 [0.3, 0.5] L; mean follow-up: ∼6 years; n = 82) and were stable in subjects ≥18 years (mean change: 0.0 [-0.0, 0.1] L and 0.0 [-0.1, 0.1] L; mean follow-up: 4.6 years; n = 38). Overall, 148 (47.1%) ERT-treated subjects experienced ≥1 adverse event (AE) and 110 subjects (35%) reported ≥1 serious AE. Drug-related AEs were reported in 39 (12.4%) subjects; the most common were hypersensitivity (9 subjects [2.9%]), urticaria (8 subjects [2.5%]), and pyrexia (7 subjects [2.2%]).
MARS is the longest and largest observational study of MPS IVA patients to date, with a heterogenous population that is representative of the MPS IVA population overall. Data collected over the first 6 years of MARS provide real-world evidence for long-term stabilization of endurance and respiratory function among ERT-treated patients, with no new safety concerns identified.
莫氏关节炎注册研究（MARS）是一项正在进行的、多国的、观察性研究，研究对象为莫氏关节炎 IVA 患者。MARS 的主要目标是描述疾病的异质性和自然史，并评估艾罗硫酸酯阿尔法酶替代疗法（ERT）的长期疗效和安全性。该研究于 2014 年 9 月开始招募受试者；作为常规护理的一部分，收集了受试者的病史、临床结局和安全性评估数据。
截至 2021 年 2 月，已有来自 17 个国家的 381 名受试者入组 MARS：58 名 ERT 初治受试者和 323 名 ERT 治疗受试者（≥1 次输注），ERT 暴露中位时间为 5.5 年（SD 2.8），首次 ERT 治疗的中位年龄为 9.8 岁。与 ERT 初治受试者相比，ERT 治疗受试者的诊断年龄更小（中位年龄：3.4 岁 vs 6.5 岁）。在 ERT 治疗受试者中，尿硫酸角质素（uKS）水平从 ERT 前基线降至末次随访时的治疗水平（平均百分比变化[95%置信区间]：-52.5%[-57.5%，-47.4%]；n=115），6 分钟步行试验距离在 ERT 治疗 5.5 年的中位随访期间保持稳定（平均变化：-6.1[-27.6，15.5]m；n=131）。在 ERT 起始年龄<18 岁的受试者中，第 1 秒用力呼气量（FEV）和用力肺活量（FVC）增加（平均变化：+0.3[0.1，0.4]L 和+0.4[0.3，0.5]L；平均随访时间：约 6 年；n=82），而 ERT 起始年龄≥18 岁的受试者中 FEV 和 FVC 保持稳定（平均变化：0.0[-0.0，0.1]L 和 0.0[-0.1，0.1]L；平均随访时间：4.6 年；n=38）。总体而言，148（47.1%）名 ERT 治疗受试者出现了≥1 次不良事件（AE），110 名（35%）受试者报告了≥1 次严重 AE。报告了与药物相关的 AE 有 39 例（12.4%）；最常见的是过敏反应（9 例[2.9%]）、荨麻疹（8 例[2.5%]）和发热（7 例[2.2%]）。
MARS 是迄今为止关于莫氏关节炎 IVA 患者最长和最大的观察性研究，其患者人群具有异质性，代表了总体莫氏关节炎 IVA 人群。MARS 研究前 6 年的数据提供了 ERT 治疗患者耐力和呼吸功能长期稳定的真实世界证据，未发现新的安全性问题。
