Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis
Authors: 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 
Published: September 2022

Objective

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.

Methods

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.

Results

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.

Conclusions

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.