NEJM：新药物BG-12有助防止多发性硬化症复发

一项最新研究证实每天两次使用新药物BG-12，多发性硬化症患者疾病年复发率减少近一半。俄亥俄州克利夫兰诊所Robert Fox博士说：我们发现每天两次服用该新药物，疾病年复发率减少44％，每日服用三次该新药物的话，疾病复发率减少51％。Fox补充说，药物的耐受性良好，在临床试验中证明是相当安全的。。

研究结果发表在9月20日的New England Journal of Medicine上。多发性硬化症是一种慢性、炎症性、脱髓鞘的中枢神经系统疾病。可引起各种症状，包括感觉改变、视觉障碍、肌肉无力、忧郁、协调与讲话困难、严重的疲劳、认知障碍、平衡障碍、体热和疼痛等，严重的可以导致活动性障碍和残疾。

多发性硬化症影响脑和脊髓的神经细胞──神经元。神经元传递信息，形成思维和感觉，以使大脑控制身体。保护这些神经元的脂肪层为髓鞘(Myelin Sheath)，协助神经元进行电信号传递。多发性硬化症逐渐造成大脑和脊髓的斑块性的神经髓鞘的破坏(脱髓鞘)，髓鞘的瘢痕形成影响神经轴突的信号传递，以失去大脑和脊髓对外周的控制，以至多部位的僵硬或丧失功能。
 
多发性硬化症的平均发病年龄一般在20至40岁，女性发病人数两倍于男性。多发性硬化症的病因不清，多被认为是自身免疫性疾病。少数人认为是一种代谢依赖性神经变性疾病。目前尚无有效的治疗办法。

目前的研究都集中在复发缓解型多发性硬化症患者。Fox的研究包括359名服用240毫克BG-12（一天两次）的病人，345名服用240毫克（一天三次）的患者，350名服用醋酸格拉默的MS患者和363名服用安慰剂者。

BG-12最初是作为治疗自身免疫性皮肤疾病牛皮癣来开发研究的。每日服用两次BG-12的患者，多发性硬化症年复发率为0.22，对于那些每日服用3次BG-12的患者，多发性硬化症年复发率为为0.20。服用醋酸格拉替雷的患者，年复发率为0.29，而安慰剂对照组，复发率为0.40。研究表明BG-12对复发性多发性硬化症有效，可以帮助防止多发性硬化症（MS）复发。

doi:N Engl J Med 2012; 367:1087-1097
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Placebo-Controlled Phase 3 Study of Oral BG-12 or Glatiramer in Multiple Sclerosis

Robert J. Fox, M.D., David H. Miller, M.D., J. Theodore Phillips, M.D., Ph.D., Michael Hutchinson, F.R.C.P., Eva Havrdova, M.D., Mariko Kita, M.D., Minhua Yang, M.S., Kartik Raghupathi, M.S., Mark Novas, M.D., Marianne T. Sweetser, M.D., Ph.D., Vissia Viglietta, M.D., Ph.D., and Katherine T. Dawson, M.D. for the CONFIRM Study Investigators

Background BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing–remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate).

Methods In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing–remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate.

Results At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T2-weighted hyperintense lesions (all P<0.001) and new T1-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T2-weighted hyperintense lesions (both BG-12 doses), and new T1-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12.

Conclusions In patients with relapsing–remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.)