INSERM U 1215, University of Bordeaux, Bordeaux, France.
Zuyderland Medisch Centrum Sittard, Maastricht University Medical Center, Maastricht, the Netherlands.
Mult Scler Relat Disord. 2022 Jan;57:103385. doi: 10.1016/j.msard.2021.103385. Epub 2021 Nov 9.
Background Multiple sclerosis (MS) is a chronic disabling disease that is associated with negative effects on health-related quality of life (HRQoL) due to reduced physical and psychosocial functioning. Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) have been approved for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS). The ongoing CLARIFY-MS study (NCT03369665; EudraCT number: 2017-002632-17) aims to assess the effect of cladribine tablets 3.5 mg/kg on HRQoL of patients with highly active RMS. Objective To report on the design of the CLARIFY-MS study, baseline patient characteristics, and results of a pre-planned interim analysis focusing on treatment satisfaction, safety, and tolerability that includes all data reported till 6 months after start of treatment. Methods The CLARIFY-MS study is a 2-year, open-label, single-arm, prospective, multicenter, phase IV study. Eligible patients with highly active RMS were assigned to receive cladribine tablets 3.5 mg/kg over 2 years. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM, v1.4; scale range from 0 to 100, higher values indicating higher satisfaction). Safety assessments, including occurrence of treatment-emergent adverse events (TEAEs; any adverse event reported after drug administration), serious adverse events (SAEs), and lymphocyte counts, were summarized descriptively. Results A total of 482 patients from 85 sites in Europe were treated with cladribine tablets. Mean patient age was 37.4 years, 338 (70.1%) were women, median EDSS was 2.5, and 345 (71.6%) were prior users of disease-modifying therapy (DMT). During the first 6 months after the start of treatment, and before reaching the full dose of cladribine tablets, mean TSQM global satisfaction score for the overall population was 70.4 (standard deviation, ± 18.48). The side effects score was 91.9 (± 17.68), convenience scored 86.6 (± 13.57), and effectiveness was 65.8 (± 21.14). A total of 275 patients (57.1%) reported at least one TEAE and 9 patients (1.9%) had a SAE. The majority of observed lymphopenia cases were of grade 1 or 2; 33 (6.8%) of the total study cohort had grade 3 lymphopenia, and no grade 4 lymphopenia was reported. Conclusion Patients reported high treatment satisfaction (TSQM) with cladribine tablets in this pre-planned interim analysis at 6 months. Few serious, and no unexpected, adverse events were reported, and there were no instances of grade 4 lymphopenia over the first 6 months. These preliminary data indicate good tolerability and convenience of administration of cladribine tablets in patients with highly active RMS.
多发性硬化症（MS）是一种慢性致残性疾病，由于身体和心理社会功能下降，导致健康相关生活质量（HRQoL）受到负面影响。克拉屈滨片剂 10mg（2 年内累积剂量 3.5mg/kg）已获准用于治疗活动期高复发多发性硬化症（RMS）的成年患者。正在进行的 CLARIFY-MS 研究（NCT03369665；EudraCT 编号：2017-002632-17）旨在评估克拉屈滨片剂 3.5mg/kg 对高活性 RMS 患者 HRQoL 的影响。
报告 CLARIFY-MS 研究的设计、基线患者特征以及预先计划的中期分析结果，重点关注治疗满意度、安全性和耐受性，该分析包括治疗开始后 6 个月报告的所有数据。
CLARIFY-MS 研究是一项为期 2 年、开放标签、单臂、前瞻性、多中心、IV 期研究。符合条件的高活性 RMS 患者被分配接受克拉屈滨片剂 3.5mg/kg，持续 2 年。使用治疗满意度问卷药物版（TSQM，v1.4；评分范围为 0 至 100，得分越高表示满意度越高）评估治疗满意度。安全性评估包括治疗后出现的不良事件（TEAE；治疗后报告的任何不良事件）、严重不良事件（SAE）和淋巴细胞计数，均进行描述性总结。
来自欧洲 85 个地点的 482 名患者接受了克拉屈滨片剂治疗。患者平均年龄为 37.4 岁，338 名（70.1%）为女性，中位 EDSS 为 2.5，345 名（71.6%）为疾病修正治疗（DMT）的既往使用者。在治疗开始后最初的 6 个月内，在达到克拉屈滨片剂全剂量之前，总体人群的平均 TSQM 总体满意度评分为 70.4（标准差，±18.48）。副作用评分为 91.9（±17.68），便利性评分为 86.6（±13.57），有效性为 65.8（±21.14）。共有 275 名患者（57.1%）报告了至少 1 例不良事件，9 名患者（1.9%）发生了 SAE。观察到的大多数淋巴细胞减少症病例为 1 级或 2 级；总研究队列中有 33 名（6.8%）患者发生 3 级淋巴细胞减少症，无 4 级淋巴细胞减少症报告。
在预先计划的中期分析中，在治疗开始后 6 个月时，患者报告克拉屈滨片剂治疗的满意度（TSQM）较高。报告的严重不良事件较少，且无意外不良事件，在最初的 6 个月内无 4 级淋巴细胞减少症发生。这些初步数据表明，克拉屈滨片剂在治疗高活性 RMS 患者时具有良好的耐受性和便利性。
