Kamm Christian P, El-Koussy Marwan, Humpert Sebastian, Findling Oliver, Burren Yuliya, Schwegler Guido, Donati Filippo, Müller Martin, Müller Felix, Slotboom Johannes, Kappos Ludwig, Naegelin Yvonne, Mattle Heinrich P
Department of Neurology, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
PLoS One. 2014 Jan 30;9(1):e86663. doi: 10.1371/journal.pone.0086663. eCollection 2014.
Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects.
To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS).
In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study.
27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated.
Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months.
ClinicalTrials.gov NCT01111656.
他汀类药物除具有降脂作用外，还具有抗炎和免疫调节特性。
报告一项II期试验的12个月延长期研究结果，该试验评估了在复发缓解型多发性硬化症（RRMS）患者中，40mg/d阿托伐他汀联合β-1b干扰素（IFNB-1b）治疗的疗效、安全性和耐受性。
在随机、多中心、平行组、评估者盲法的核心研究中，77例RRMS患者开始接受IFNB-1b治疗。在第3个月时，他们被1∶1随机分组，在继续接受IFNB-1b治疗的基础上，一组加用40mg/d阿托伐他汀，另一组不加用，直至第15个月。在随后的延长期研究中，患者继续使用原治疗方案，持续12个月。将研究结束时的数据与核心研究第3个月时的数据进行比较。
完成核心研究的72例患者中有27例进入延长期研究。45例患者失访，主要原因是核心研究期间的安全性分析，包括延长期研究的招募终止。主要终点指标，即T2加权像上新病灶患者的比例，两组间无差异（优势比1.926；95%可信区间0.265-14.0007；p=0.51）。所有次要终点指标，包括T2加权像上新病灶数量和总病灶体积、T1加权像上钆增强病灶总数、灰质和白质体积、扩展残疾状态量表（EDSS）、多发性硬化功能复合量表（MSFC）、复发率、无复发患者数量及中和抗体等，均无显著差异。联合治疗耐受性良好。
在24个月的研究期内，与IFNB-1b单药治疗相比，IFNB-1b联合40mg/d阿托伐他汀对RRMS患者无任何有益作用。
ClinicalTrials.gov NCT01111656。
