Ticha Veronika, Kalincik Tomas, Havrdova Eva
Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, First Faculty of Medicine and General University Hospital in Prague, Czech Republic.
Neurol Res. 2012 Dec;34(10):923-30. doi: 10.1179/1743132812Y.0000000090. Epub 2012 Aug 21.
To evaluate safety and efficacy of add-on low-dose azathioprine or interferon (IFN)-beta in patients with active multiple sclerosis despite monotherapy.
This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either IFN-beta or azathioprine, who received add-on azathioprine or IFN-beta, respectively. In a subgroup of 23 patients, 10-year data were analysed. Clinical (relapse frequency, disability) and laboratory effects were compared preceding and following the addition of second drug and between the two treatment regimens. Potential serious adverse events were evaluated.
The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts decreased, being below the physiological levels in 8-26% and 13-52% of patients at each time point, respectively. The drop in relapse rate was independent from the dosage of azathioprine or changes in lymphocyte count. Comparison between the two treatment regimens showed that, with the exception of lymphocyte count, these effects were triggered by the add-on of interferon but not azathioprine. The combination therapy was well tolerated; however, after 5 years on treatment a moderately increased incidence of cancer was observed.
IFN-beta as add-on to azathioprine decreases relapse activity in active multiple sclerosis. In contrast, azathioprine add-on in patients with suboptimal response to IFN-beta does not improve the control over the disease activity.
评估在单一疗法治疗无效的活动性多发性硬化症患者中加用低剂量硫唑嘌呤或干扰素（IFN）-β的安全性和有效性。
这项回顾性观察性研究评估了85例尽管接受了IFN-β或硫唑嘌呤单一疗法但仍患有活动性多发性硬化症的患者的5年数据，这些患者分别接受了加用硫唑嘌呤或IFN-β的治疗。在一个23例患者的亚组中，分析了10年数据。比较了加用第二种药物之前和之后以及两种治疗方案之间的临床（复发频率、残疾情况）和实验室效应。评估了潜在的严重不良事件。
加用治疗使年化复发率在5年和10年期间持续下降约1.5个百分点。未观察到对残疾情况有影响。同时，白细胞和淋巴细胞计数下降，在每个时间点分别有8%-26%和13%-52%的患者低于生理水平。复发率的下降与硫唑嘌呤的剂量或淋巴细胞计数的变化无关。两种治疗方案的比较表明，除淋巴细胞计数外，这些效应是由加用干扰素而非硫唑嘌呤引发的。联合治疗耐受性良好；然而，治疗5年后观察到癌症发病率适度增加。
在硫唑嘌呤基础上加用IFN-β可降低活动性多发性硬化症的复发活动。相比之下，对IFN-β反应欠佳的患者加用硫唑嘌呤并不能改善对疾病活动的控制。
