Multiple Sclerosis Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
PLoS One. 2011 Feb 3;6(2):e16664. doi: 10.1371/journal.pone.0016664.
Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown.
This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch.
In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004).
Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.
在免疫调节药物突破性疾病的多发性硬化症（MS）患者中，经常会被建议转换为那他珠单抗或免疫抑制剂。突破性疾病患者接受那他珠单抗单药治疗的效果尚不清楚。
这是一项在加利福尼亚大学旧金山分校 MS 中心至少接受过 4 次就诊的 993 例患者的开放性回顾性队列研究，95 例患者在一线治疗中出现突破性疾病（60 例患者转换为那他珠单抗，22 例转换为免疫抑制剂，13 例拒绝转换[非转换者]）。我们使用泊松回归调整潜在混杂因素，比较转换前后组内和组间的复发率。
在组内分析中，转换为那他珠单抗的患者复发率降低了 70%（95%可信区间 50，82%；p<0.001），转换为免疫抑制剂的患者降低了 77%（95%可信区间 59，87%；p<0.001）；而非转换者的复发率并未降低（6%，p = 0.87）。与非转换者相比，那他珠单抗转换者的复发率降低了 68%（95%可信区间 19，87%；p = 0.017），免疫抑制剂转换者降低了 76%（95%可信区间 36，91%；p = 0.004）。
在突破性疾病患者中转换为那他珠单抗或免疫抑制剂可有效降低复发性 MS 的临床活动度。在随机临床试验和前瞻性队列研究中，应评估其效果的大小和风险效益比。
