Alshamrani Foziah, Alnajashi Hind, Almuaigel Mohammed F
Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Al Khobar, SAU.
Department of Medicine, King Abdulaziz University, Jeddah, SAU.
Cureus. 2020 Feb 14;12(2):e6995. doi: 10.7759/cureus.6995.
Background Multiple sclerosis (MS) is an autoimmune and demyelinating inflammatory disease that affects the central nervous system (CNS). The etiology of the disease remains unknown. Multiple theories highlight genetic, environmental, and infectious factors that may a role. MS is considered as the main cause of disability in young people. Cladribine, known chemically as (2-Chloro-2'-deoxyadenosine), is a purine analog chemotherapy used for hairy cell leukemia and other B-cell lymphomas. The goal of this study was to evaluate the safety and efficacy of cladribine in patients with rapidly evolving or early secondary progressive MS. Methods This observational, single-center, retrospective chart review at the MS Clinic in the Ottawa General Hospital, Ottawa, Canada. A total of 24 patients (median Expanded Disability Status Scale (EDSS) of 4.5) received cladribine (0.07 mg/kg/day) for four consecutive days every six months for ≥ 2 cycles with further cycles depending on lymphocyte recovery or disease activity to a maximum of eight cycles from 2005 until 2016 were included. Four patients who were already diagnosed with rapidly evolving or early secondary progressive multiple sclerosis (SPMS) were induced with cladribine. We evaluated relapse, EDSS, and magnetic resonance imaging (MRI) results. Results Out of 24 patients (ages ranging from 30 - 60), 80% were female. Median follow-up time was seven years. The mean relapse rate in the two years before patients were given cladribine was 1.25. Twenty patients had previously received multiple disease-modifying therapies (DMTs) (≥ 2) prior to receiving cladribine. Following cladribine, eight patients suffered 10 relapses (33.3% of the cohort). Annualized relapse rates (ARRs) were reduced from 1.25 to 0.42, which was statistically significant (p-value = 0.002). There was no mean difference in EDSS (p-value = 0.06): 16% deteriorated, 62% did not change, and 12.5% improved. New MRI activity (new T2 or Gad+ lesions) was noted in only seven of 24 patients. Conclusion Parenteral cladribine reduced the relapse rate from 1.25 to 0.42, which was statistically significant (p-value = 0.002). MRI activity in patients with rapidly evolving or early secondary progressive multiple sclerosis had a reasonable safety profile.
多发性硬化症（MS）是一种影响中枢神经系统（CNS）的自身免疫性脱髓鞘炎症性疾病。该疾病的病因尚不清楚。多种理论强调了可能起作用的遗传、环境和感染因素。MS被认为是年轻人残疾的主要原因。克拉屈滨，化学名称为（2-氯-2'-脱氧腺苷），是一种用于毛细胞白血病和其他B细胞淋巴瘤的嘌呤类似物化疗药物。本研究的目的是评估克拉屈滨在快速进展型或早期继发进展型MS患者中的安全性和有效性。
在加拿大渥太华渥太华综合医院的MS诊所进行的这项观察性、单中心、回顾性病历审查。共有24例患者（扩展残疾状态量表（EDSS）中位数为4.5）从2005年至2016年每六个月连续四天接受克拉屈滨（0.07 mg/kg/天）治疗，≥2个周期，根据淋巴细胞恢复情况或疾病活动情况进行进一步周期治疗，最多8个周期。4例已被诊断为快速进展型或早期继发进展型多发性硬化症（SPMS）的患者接受了克拉屈滨诱导治疗。我们评估了复发、EDSS和磁共振成像（MRI）结果。
24例患者（年龄在30 - 60岁之间）中，80%为女性。中位随访时间为7年。患者接受克拉屈滨治疗前两年的平均复发率为1.25。20例患者在接受克拉屈滨治疗前曾接受过多种疾病修饰疗法（DMTs）（≥2种）。接受克拉屈滨治疗后，8例患者发生10次复发（占队列的33.3%）。年化复发率（ARRs）从1.25降至0.42，具有统计学意义（p值 = 0.002）。EDSS无均值差异（p值 = 0.06）：16%恶化，62%无变化，12.5%改善。24例患者中仅7例出现新的MRI活动（新的T2或钆增强病变）。
静脉注射克拉屈滨将复发率从1.25降至0.42，具有统计学意义（p值 = 0.002）。快速进展型或早期继发进展型多发性硬化症患者的MRI活动具有合理的安全性。
