Landi Doriana, Bovis Francesca, Grimaldi Alfonso, Annovazzi Pietro Osvaldo, Bertolotto Antonio, Bianchi Alessia, Borriello Giovanna, Brescia Morra Vincenzo, Bucello Sebastiano, Buscarinu Maria Chiara, Caleri Francesca, Capobianco Marco, Capra Ruggero, Cellerino Maria, Centonze Diego, Cerqua Raffaella, Chisari Clara Grazia, Clerico Marinella, Cocco Eleonora, Cola Gaia, Cordioli Cinzia, Curti Erica, d'Ambrosio Alessandro, D'Amico Emanuele, De Luca Giovanna, Di Filippo Massimiliano, Di Lemme Sonia, Fantozzi Roberta, Ferraro Diana, Ferraro Elisabetta, Gallo Antonio, Gasperini Claudio, Granella Franco, Inglese Matilde, Lanzillo Roberta, Lorefice Lorena, Lus Giacomo, Malucchi Simona, Margoni Monica, Mataluni Giorgia, Mirabella Massimiliano, Moiola Lucia, Nicoletti Carolina Gabri, Nociti Viviana, Patti Francesco, Pinardi Federica, Portaccio Emilio, Pozzilli Carlo, Ragonese Paolo, Rasia Sarah, Salemi Giuseppe, Signoriello Elisabetta, Vitetta Francesca, Totaro Rocco, Sormani Maria Pia, Amato Maria Pia, Marfia Girolama Alessandra
Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy
Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
J Neurol Neurosurg Psychiatry. 2022 Sep 30. doi: 10.1136/jnnp-2022-329657.
Assessing the risk of clinical and radiological reactivation during pregnancy and post partum in women with multiple sclerosis (MS) treated with natalizumab (NTZ) throughout pregnancy (LONG_EXP) compared with women interrupting treatment before (NO_EXP) and within >-30 days and ≤90 days from conception (SHORT_EXP), and describing newborns' outcomes.
Maternal clinical and radiological outcomes and obstetric and fetal outcomes were retrospectively collected and compared among groups (NO_EXP, SHORT_EXP, LONG_EXP). Predictors of clinical and radiological reactivation were investigated through univariable and multivariable analysis.
170 eligible pregnancies from 163 women referring to 29 Italian MS centres were included. Annualised relapse rate (ARR) was significantly lower in LONG_EXP (n=66, 0.02 (0.001-0.09)) compared with NO_EXP (n=31, 0.43 (0.21-0.75), p=0.002) and SHORT_EXP (n=73, 0.46 (0.30-0.66), p=0.0004) during pregnancy, and in LONG_EXP (0.12 (0.05-0.24)) compared with SHORT_EXP (0.30 (0.17-0.50), p=0.008) during post partum. Gadolinium-enhancing (Gd+) lesions were less frequent in LONG_EXP (n=6/50, 2.00%) compared with NO_EXP (n=9/21, 42.86%) and SHORT_EXP after delivery (n=17/49, 34.69%, p=0.010).Delaying NTZ resumption after delivery significantly increased the risk of relapses (OR=1.29 (95% CI 1.07 to 1.57), p=0.009) and Gd+ lesions (OR=1.49 (95% CI 1.17 to 1.89, p=0.001). Newborns' weight, length, head circumference and gestational age did not differ among groups after adjusting for confounders. Anaemia was tracked in 4/69 LONG_EXP newborns. Congenital anomaly rate was within the expected range for the untreated MS population.
Our findings indicate that in women with MS treated with NTZ before conception, continuation of NTZ throughout pregnancy and its early resumption after delivery mitigate the risk of clinical and radiological reactivation. This approach has no major impact on newborns' outcomes.
评估在整个孕期接受那他珠单抗（NTZ）治疗的多发性硬化症（MS）女性患者（长期治疗组）与在受孕前中断治疗的女性患者（未治疗组）以及在受孕后超过 -30 天且≤90 天中断治疗的女性患者（短期治疗组）在妊娠和产后临床及影像学复发的风险，并描述新生儿结局。
回顾性收集并比较各组（未治疗组、短期治疗组、长期治疗组）的孕产妇临床和影像学结局以及产科和胎儿结局。通过单变量和多变量分析研究临床和影像学复发的预测因素。
纳入了来自 29 个意大利 MS 中心的 163 名女性的 170 例符合条件的妊娠。与未治疗组（n = 31，0.43（0.21 - 0.75），p = 0.002）和短期治疗组（n = 73，0.46（0.30 - 0.66），p = 0.0004）相比，长期治疗组（n = 66，0.02（0.001 - 0.09））在孕期的年化复发率（ARR）显著更低；与短期治疗组（n = 73，0.30（0.17 - 0.50），p = 0.008）相比，长期治疗组（0.12（0.05 - 0.24））在产后的年化复发率也更低。与未治疗组（n = 9/21，42.86%）和产后短期治疗组（n = 17/49，34.69%，p = 0.010）相比，长期治疗组（n = 6/50，2.00%）钆增强（Gd +）病灶较少。产后延迟恢复 NTZ 治疗显著增加了复发风险（比值比（OR）= 1.29（95%置信区间 1.07 至 1.57），p = 0.009）和 Gd + 病灶风险（OR = 1.49（95%置信区间 1.17 至 1.89，p = 0.001）。在调整混杂因素后，各组新生儿的体重、身长、头围和胎龄无差异。在长期治疗组的 69 例新生儿中有 4 例追踪到贫血。先天性异常率在未治疗的 MS 人群预期范围内。
我们的研究结果表明，对于受孕前接受 NTZ 治疗的 MS 女性患者，整个孕期持续使用 NTZ 并在产后早期恢复使用可降低临床和影像学复发的风险。这种方法对新生儿结局没有重大影响。
