Background

Multiple sclerosis (MS) is a chronic inflammatory, immune-mediated disease affecting the central nervous system. Natalizumab, an FDA-approved monoclonal antibody for MS, has been explored for its off-label extended interval dosing (EID), suggesting a potential reduction in the risk of progressive multifocal leukoencephalopathy (PML) compared to standard interval dosing (SID). Our objective was to assess the efficacy and safety of EID in comparison to SID for natalizumab treatment in patients with MS.

Methods

We searched PubMed, Embase, WOS, Scopus, Ovid, Science Direct, Clinical trials.gov, and Cochrane Library. Our assessed outcomes were clinical relapses, MRI activity, change in expanded disability status scale [EDSS], and the risk of PML. The EID group was defined as 5 to 8 weeks [EID (Q5-8W)]. The analysis was conducted using RevMan ver. 5.4. The effect estimates were presented as a risk ratio [RR] or mean difference with 95% confidence intervals [CI] using SID group as the reference for comparisons.

Results

Fourteen studies met our inclusion criteria: 2 RCTs, 1 switched single-arm trial, and 12 observational studies. No significant differences were found in all efficacy outcomes of interest. Risk of clinical relapses [RR = 0.90, (95%CI 0.80, 1.02)], risk of new or newly enlarging T2 hyperintense MRI lesions [RR = 0.78, (95%CI 0.59, 1.04)], risk gadolinium enhancing lesions [RR = 1.30, (95%CI 0.98, 1.72)], change in EDSS [MD = 0.09 (95%CI − 0.57, 0.76)], risk of PML [RR = 1.09, 95%CI (0.24, 4.94)].

Conclusion

In summary, our meta-analysis indicates that natalizumab maintains its effectiveness under extended interval dosing [up to 8 weeks], presenting comparable risks for clinical relapses, MRI lesions, EDSS, and PML. Caution is advised given study limitations and heterogeneity. Robust conclusions necessitate well-designed high-quality prospective studies.

中文翻译：

---

那他珠单抗延长给药与标准间隔给药在多发性硬化症患者中的安全性和有效性：系统评价和荟萃分析

背景

多发性硬化症 (MS) 是一种影响中枢神经系统的慢性炎症、免疫介导疾病。那他珠单抗是 FDA 批准的治疗多发性硬化症的单克隆抗体，已对其标签外延长间隔给药 (EID) 进行了探索，表明与标准间隔给药 (SID) 相比，可能降低进行性多灶性白质脑病 (PML) 的风险。我们的目的是评估那他珠单抗治疗 MS 患者时 EID 与 SID 的疗效和安全性。

方法

我们检索了 PubMed、Embase、WOS、Scopus、Ovid、Science Direct、Clinical Trials.gov 和 Cochrane Library。我们评估的结果是临床复发、MRI 活动、扩展残疾状态量表 [EDSS] 的变化以及 PML 风险。EID 组定义为 5 至 8 周 [EID (Q5-8W)]。使用 RevMan ver. 进行分析。5.4. 效果估计以风险比 [RR] 或平均差与 95% 置信区间 [CI] 的形式呈现，使用 SID 组作为比较参考。

结果

14 项研究符合我们的纳入标准：2 项随机对照试验、1 项转换单臂试验和 12 项观察性研究。所有感兴趣的疗效结果均未发现显着差异。临床复发风险 [RR = 0.90, (95%CI 0.80, 1.02)]、新出现或新扩大的 T2 高信号 MRI 病变风险 [RR = 0.78, (95%CI 0.59, 1.04)]、钆增强病变风险 [RR = 1.30, (95%CI 0.98, 1.72)]，EDSS 变化 [MD = 0.09 (95%CI − 0.57, 0.76)]，PML 风险 [RR = 1.09, 95%CI (0.24, 4.94)]。

结论

总之，我们的荟萃分析表明那他珠单抗在延长给药间隔（长达 8 周）下仍保持其有效性，临床复发、MRI 病变、EDSS 和 PML 的风险相当。鉴于研究的局限性和异质性，建议谨慎行事。强有力的结论需要精心设计的高质量前瞻性研究。