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Abstract：
OBJECTIVE: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients.
METHODS: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts.
RESULTS: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months.
CONCLUSIONS: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
METHODS: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3-4 days during week 1. Based on lymphocyte count at week 4, patients received another 0-3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts.
RESULTS: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17-72) years and EDSS 0-8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months.
CONCLUSIONS: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
摘要：
目的：报告多发性硬化症（MS）患者皮下使用克拉屈滨（Litak®）的安全性和有效性。
方法：向MS患者提供Litak®，无论病程如何。在第1周期间施用Litak®10mg持续3-4天。根据第4周的淋巴细胞计数，患者在第5周接受了另外的0-3次剂量。11个月后进行第二个疗程。随访包括不良事件，复发,扩展残疾状况量表(EDSS)，9孔钉和定时25英尺步行测试，无疾病活动证据(NEDA)，没有进展或活跃疾病的证据(新伙伴关系)，MRI,脑脊液（CSF）神经丝轻链（NfL），和淋巴细胞计数。
结果：总而言之，208名患者接受了至少一个疗程的治疗。基线年龄为44（17-72）岁，EDSS为0-8.5。克拉屈滨一般耐受性良好。一次心肌梗塞,一个乳腺癌,发生了三次严重的皮肤反应，没有长期后遗症。两名患者死亡（一名肺炎，一种脑炎）。3级淋巴细胞减少发生率为5％，4级淋巴细胞减少发生率为0.5％。在两个疗程后的基线和随访（BaFU）数据的116个pwMS中有94个，EDSS保持稳定或改善。18个月时,64％的复发MS和BaFU患者（n=39）患有NEDA。19个月时,62%的进展性MS和BaFU患者（n=13）有新伙伴关系。在n=13例患者中，基线时CSF-NfL升高，77%在12个月内恢复正常。
结论：Litak®耐受性良好。复发性MS的有效性与克拉屈滨片相似，在进行性MS中令人鼓舞。我们的数据表明克拉屈滨在MS患者中可能是安全有效的，无论其疾病阶段如何。
方法：向MS患者提供Litak®，无论病程如何。在第1周期间施用Litak®10mg持续3-4天。根据第4周的淋巴细胞计数，患者在第5周接受了另外的0-3次剂量。11个月后进行第二个疗程。随访包括不良事件，复发,扩展残疾状况量表(EDSS)，9孔钉和定时25英尺步行测试，无疾病活动证据(NEDA)，没有进展或活跃疾病的证据(新伙伴关系)，MRI,脑脊液（CSF）神经丝轻链（NfL），和淋巴细胞计数。
结果：总而言之，208名患者接受了至少一个疗程的治疗。基线年龄为44（17-72）岁，EDSS为0-8.5。克拉屈滨一般耐受性良好。一次心肌梗塞,一个乳腺癌,发生了三次严重的皮肤反应，没有长期后遗症。两名患者死亡（一名肺炎，一种脑炎）。3级淋巴细胞减少发生率为5％，4级淋巴细胞减少发生率为0.5％。在两个疗程后的基线和随访（BaFU）数据的116个pwMS中有94个，EDSS保持稳定或改善。18个月时,64％的复发MS和BaFU患者（n=39）患有NEDA。19个月时,62%的进展性MS和BaFU患者（n=13）有新伙伴关系。在n=13例患者中，基线时CSF-NfL升高，77%在12个月内恢复正常。
结论：Litak®耐受性良好。复发性MS的有效性与克拉屈滨片相似，在进行性MS中令人鼓舞。我们的数据表明克拉屈滨在MS患者中可能是安全有效的，无论其疾病阶段如何。
