Brown J William L, Coles Alasdair J
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Drug Des Devel Ther. 2013;7:131-8. doi: 10.2147/DDDT.S32687. Epub 2013 Mar 6.
Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing-remitting multiple sclerosis. One Phase II and two Phase III trials of alemtuzumab versus active comparator (interferon beta-1a) have been reported. Two of these rater-blinded randomized studies assessed clinical and radiological outcomes in treatment-naïve patients; one explored patients who had relapsed despite first-line therapy. Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group. After alemtuzumab, the Expanded Disability Status Scale score improved by 0.14-1.2 points, culminating in a net advantage with alemtuzumab of 0.41-0.77 points over interferon in the CAMMS223 and CARE-MS2 trials (both P < 0.001). Radiological markers of new lesion formation and brain atrophy following alemtuzumab were significantly improved when compared to interferon in all studies. Adverse events were more common following alemtuzumab than interferon beta-1a (7.2-8.66 versus 4.9-5.7 events per person-year). While infusion reactions are the most common, autoimmunity is the most concerning; within Phase III studies, thyroid disorders (17%-18% versus 5%-6%) and immune thrombocytopenic purpura (1% versus 0%) were reported in patients taking alemtuzumab and interferon beta-1a, respectively. All patients responded to conventional therapy. One patient taking alemtuzumab in the Phase II study suffered a fatal intracranial hemorrhage following immune thrombocytopenic purpura, heralding assiduous monitoring of all patients thereafter. Alemtuzumab has been submitted for licensing in relapsing-remitting multiple sclerosis in the United States and Europe.
阿仑单抗（曾称为Campath(®)）是一种人源化单克隆抗体，可靶向成熟淋巴细胞上的CD52抗原，导致淋巴细胞减少并随后改变免疫库。在此，我们探讨其在复发缓解型多发性硬化症中的疗效和安全性证据。已报告了一项阿仑单抗与活性对照药（干扰素β-1a）对比的II期试验和两项III期试验。其中两项评定者设盲的随机研究评估了初治患者的临床和影像学结局；一项研究针对尽管接受一线治疗仍复发的患者。与干扰素β-1a相比，阿仑单抗使复发率降低了49%-74%（P<0.0001），并且在两项研究中使持续性残疾累积风险降低了42%-71%（P<0.01）。在一项研究（阿仑单抗与利比在多发性硬化症中的疗效比较；CARE-MS1）中，与干扰素相比无显著差异，这可能反映了对照药组中残疾事件的发生率低得出奇。接受阿仑单抗治疗后，扩展残疾状态量表评分提高了0.14-1.2分，在CAMMS223和CARE-MS2试验中，阿仑单抗相对于干扰素的净优势为0.41-0.77分（均P<0.001）。在所有研究中，与干扰素相比，阿仑单抗治疗后新病灶形成和脑萎缩的影像学标志物均有显著改善。阿仑单抗治疗后的不良事件比干扰素β-1a更常见（每人年7.2-8.66次事件对4.9-5.7次事件）。虽然输液反应最为常见，但自身免疫是最令人担忧的问题；在III期研究中，接受阿仑单抗和干扰素β-1a治疗的患者分别报告了甲状腺疾病（17%-18%对5%-6%）和免疫性血小板减少性紫癜（1%对0%）。所有患者均对常规治疗有反应。II期研究中一名接受阿仑单抗治疗的患者在发生免疫性血小板减少性紫癜后出现致命性颅内出血，此后对所有患者进行了严格监测。阿仑单抗已在美国和欧洲提交复发缓解型多发性硬化症的上市许可申请。
