Gold Ralf
University of Bochum, St. Josef-Hospital, Dept. of Neurology, Gudrunstr. 56, 44791, Bochum, Germany.
J Neurol. 2008 Mar;255 Suppl 1:51-60. doi: 10.1007/s00415-008-1008-2.
The last years have seen enormous progress in our understanding of pathophysiology of multiple sclerosis. In addition, the armamentarium of available immunomodulatory or immunosuppressive therapies has greatly increased, especially for the relapsing remitting form of the disease. Since their therapeutic efficacy is often limited in individual patients, it is conceivable that combination therapies may bring improved clinical efficacy while managing increasing side effects and toxicity. The combination of agents with additive or synergistic modes of action is of particular interest. Combination of the two classes of recognised firstline treatment, a beta-interferon and glatiramer acetate is currently under evaluation in a large Phase III trial. However, there are theoretical reasons for thinking that such a combination may not be particularly beneficial. None of the combination studies performed with beta-interferons to date have shown unequivocal evidence of benefit, including combinations with statins, natalizumab and azathioprine. On the other hand, for glatiramer acetate, the combination with mitoxantrone used as induction therapy may be of interest and preliminary data on combination with minocycline are also promising.
在过去几年中，我们对多发性硬化症病理生理学的理解取得了巨大进展。此外，可用的免疫调节或免疫抑制疗法的药物库大大增加，特别是对于复发缓解型疾病。由于它们在个体患者中的治疗效果往往有限，可以想象联合疗法可能会在管理不断增加的副作用和毒性的同时提高临床疗效。具有相加或协同作用模式的药物联合尤其令人感兴趣。两种公认的一线治疗药物，β-干扰素和醋酸格拉替雷的联合目前正在一项大型III期试验中进行评估。然而，有理论依据认为这种联合可能不会特别有益。迄今为止，使用β-干扰素进行的联合研究均未显示出明确的获益证据，包括与他汀类药物、那他珠单抗和硫唑嘌呤的联合。另一方面，对于醋酸格拉替雷，与米托蒽醌联合用作诱导疗法可能会有意义，并且与米诺环素联合的初步数据也很有前景。
