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多发性硬化症患者在妊娠和产后停用利妥昔单抗和那他珠单抗后的疾病活动情况。

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab.

机构信息

From the Department of Medicine (N.R., T.F.), Solna, Clinical Epidemiology Division, Karolinska Institutet; Department of Clinical Neuroscience (F.P., K.A.M., K.F.), Karolinska Institutet; Centrum for Neurology (F.P., K.F.), Academical Specialist Center, Stockholm, Sweden; Southern California Permanente Medical Group/Kaiser Permanente (A.M.L.-G.), Pasadena, CA; and Centre for Molecular Medicine (K.A.M.), Karolinska University Hospital, Stockholm, Sweden.

出版信息

Neurol Neuroimmunol Neuroinflamm. 2020 Oct 21;7(6). doi: 10.1212/NXI.0000000000000903. Print 2020 Nov.

Abstract

OBJECTIVE

To evaluate risks of disease reactivity during pregnancy and postpartum following rituximab (RTX) and natalizumab (NTZ) suspension in women with MS.

METHODS

An observational cohort study of all women with MS disease onset before childbirth between 2006 and 2017. Women were identified through the Swedish MS Registry, a nationwide clinical register, with substratification into 3 groups: women who suspended RTX and NTZ within 6 months before conception and women who were not treated with any disease-modifying treatment (DMT) within 1 year of conception. The primary outcome was the annualized relapse rate (ARR) during pregnancy and 1 year postpartum.

RESULTS

We identified 2,386 women with MS onset before a live birth; of these, 76 women suspended RTX and 53 suspended NTZ, and 457 were untreated within 1 year before conception. In all women, regardless of the treatment type, the ARR declined from 0.05-0.04 prepregnancy to 0.03-0.02 during pregnancy, returning to prepregnancy rates at 3-6 months (0.05) postpartum. In the suspended cohort, 76% (98/129) of women resumed a DMT after delivery. The relapse rate 1 year postpartum was significantly higher in the suspended NTZ women compared with the suspended RTX women (adjusted rate ratio [aRR] 7.65, 95% CI 2.47-23.6) and was lower in the suspended RTX women compared with the untreated women (aRR 0.21, 95% CI 0.08-0.61).

CONCLUSION

Disease reactivity during the postpartum period was lower among women with MS who suspended RTX before pregnancy, relative to those who suspended NTZ and untreated women. These findings suggest that RTX may exert long-acting effects on MS disease activity that encompass pregnancy and postpartum periods.

CLASSIFICATION OF EVIDENCE

This study provides Class IV evidence that in patients with MS who were on treatment before pregnancy, RTX reduces clinical disease activity compared with NTZ in the postpartum period.

摘要

目的

评估女性多发性硬化症(MS)患者在接受利妥昔单抗(RTX)和那他珠单抗(NTZ)停药后怀孕期间和产后的疾病反应风险。

方法

这是一项对 2006 年至 2017 年间分娩前发病的所有 MS 女性的观察性队列研究。通过全国性临床登记的瑞典 MS 登记处确定女性,细分为 3 组:受孕前 6 个月内停止 RTX 和 NTZ 的女性和受孕前 1 年内未接受任何疾病修正治疗(DMT)的女性。主要结局是怀孕期间和产后 1 年内的年化复发率(ARR)。

结果

我们确定了 2386 名分娩前 MS 发病的女性;其中 76 名女性停止了 RTX,53 名女性停止了 NTZ,457 名女性在受孕前 1 年内未接受治疗。在所有女性中,无论治疗类型如何,ARR 从受孕前的 0.05-0.04 降至怀孕期间的 0.03-0.02,并在产后 3-6 个月(0.05)恢复至受孕前的水平。在停药组中,76%(98/129)的女性在分娩后恢复了 DMT。与停止使用 NTZ 的女性相比,停止使用 RTX 的女性产后 1 年的复发率显著更高(调整后的比率比 [aRR] 7.65,95%CI 2.47-23.6),与未接受治疗的女性相比,复发率较低(aRR 0.21,95%CI 0.08-0.61)。

结论

与停止使用 NTZ 和未接受治疗的女性相比,在受孕前停止使用 RTX 的 MS 女性在产后期间的疾病反应较低。这些发现表明,RTX 可能对包括怀孕和产后期间的 MS 疾病活动产生长效作用。

分类证据

本研究提供了 IV 级证据,表明在受孕前接受治疗的 MS 患者中,与 NTZ 相比,RTX 在产后期间可降低临床疾病活动度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a97/7641107/9b378c9102f1/NEURIMMINFL2019025924f1.jpg

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