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

Doriana Landi; Francesca Bovis; Alfonso Grimaldi; Pietro Osvaldo Annovazzi; Antonio Bertolotto; Alessia Bianchi; Giovanna Borriello; Vincenzo Brescia Morra; Sebastiano Bucello; Maria Chiara Buscarinu; Francesca Caleri; Marco Capobianco; Ruggero Capra; Maria Cellerino; Diego Centonze; Raffaella Cerqua; Clara Grazia Chisari; Marinella Clerico; Eleonora Cocco; Gaia Cola; Cinzia Cordioli; Erica Curti; Alessandro D'Ambrosio; Emanuele D'Amico; Giovanna De Luca; Massimiliano Di Filippo; Sonia Di Lemme; Roberta Fantozzi; Diana Ferraro; Elisabetta Ferraro; Antonio Gallo; Claudio Gasperini; Franco Granella; Matilde Inglese; Roberta Lanzillo; Lorena Lorefice; Giacomo Lus; Simona Malucchi; Monica Margoni; Giorgia Mataluni; Massimiliano Mirabella; Lucia Moiola; Carolina Gabri Nicoletti; Viviana Nociti; Francesco Patti; Federica Pinardi; Emilio Portaccio; Carlo Pozzilli; Paolo Ragonese; Sarah Rasia; Giuseppe Salemi; Elisabetta Signoriello; Francesca Vitetta; Rocco Totaro; Maria Pia Sormani; Maria Pia Amato; Girolama Alessandra Marfia

doi:10.1136/jnnp-2022-329657

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

Doriana Landi, Francesca Bovis, Alfonso Grimaldi, Pietro Osvaldo Annovazzi, Antonio Bertolotto, Alessia Bianchi, Giovanna Borriello, Vincenzo Brescia Morra, Sebastiano Bucello, Maria Chiara Buscarinu, Francesca Caleri, Marco Capobianco, Ruggero Capra, Maria Cellerino, Diego Centonze, Raffaella Cerqua, Clara Grazia Chisari, Marinella Clerico, Eleonora Cocco, Gaia ColaCinzia Cordioli, Erica Curti, Alessandro D'Ambrosio, Emanuele D'Amico, Giovanna De Luca, Massimiliano Di Filippo, Sonia Di Lemme, Roberta Fantozzi, Diana Ferraro, Elisabetta Ferraro, Antonio Gallo, Claudio Gasperini, Franco Granella, Matilde Inglese, Roberta Lanzillo, Lorena Lorefice, Giacomo Lus, Simona Malucchi, Monica Margoni, Giorgia Mataluni, Massimiliano Mirabella, Lucia Moiola, Carolina Gabri Nicoletti, Viviana Nociti, Francesco Patti, Federica Pinardi, Emilio Portaccio, Carlo Pozzilli, Paolo Ragonese, Sarah Rasia, Giuseppe Salemi, Elisabetta Signoriello, Francesca Vitetta, Rocco Totaro, Maria Pia Sormani, Maria Pia Amato, Girolama Alessandra Marfia

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Abstract

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.

Original language	English
Pages (from-to)	1306-1316
Number of pages	11
Journal	Journal of Neurology, Neurosurgery and Psychiatry
Volume	93
Issue number	12
DOIs	https://doi.org/10.1136/jnnp-2022-329657
State	Published - 30 Sep 2022
Externally published	Yes

Keywords

MRI
multiple sclerosis
obstetrics

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10.1136/jnnp-2022-329657

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Landi, D., Bovis, F., Grimaldi, A., Annovazzi, P. O., Bertolotto, A., Bianchi, A., Borriello, G., Brescia Morra, V., Bucello, S., Buscarinu, M. C., Caleri, F., Capobianco, M., Capra, R., Cellerino, M., Centonze, D., Cerqua, R., Chisari, C. G., Clerico, M., Cocco, E., ... Marfia, G. A. (2022). Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 93(12), 1306-1316. https://doi.org/10.1136/jnnp-2022-329657

@article{2c463d6dd2ec4c878bd0466a047b7184,

title = "Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis",

abstract = "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.",

keywords = "MRI, multiple sclerosis, obstetrics",

author = "Doriana Landi and Francesca Bovis and Alfonso Grimaldi and Annovazzi, {Pietro Osvaldo} and Antonio Bertolotto and Alessia Bianchi and Giovanna Borriello and {Brescia Morra}, Vincenzo and Sebastiano Bucello and Buscarinu, {Maria Chiara} and Francesca Caleri and Marco Capobianco and Ruggero Capra and Maria Cellerino and Diego Centonze and Raffaella Cerqua and Chisari, {Clara Grazia} and Marinella Clerico and Eleonora Cocco and Gaia Cola and Cinzia Cordioli and Erica Curti and Alessandro D'Ambrosio and Emanuele D'Amico and {De Luca}, Giovanna and {Di Filippo}, Massimiliano and {Di Lemme}, Sonia and Roberta Fantozzi and Diana Ferraro and Elisabetta Ferraro and Antonio Gallo and Claudio Gasperini and Franco Granella and Matilde Inglese and Roberta Lanzillo and Lorena Lorefice and Giacomo Lus and Simona Malucchi and Monica Margoni and Giorgia Mataluni and Massimiliano Mirabella and Lucia Moiola and Nicoletti, {Carolina Gabri} and Viviana Nociti and Francesco Patti and Federica Pinardi and Emilio Portaccio and Carlo Pozzilli and Paolo Ragonese and Sarah Rasia and Giuseppe Salemi and Elisabetta Signoriello and Francesca Vitetta and Rocco Totaro and Sormani, {Maria Pia} and Amato, {Maria Pia} and Marfia, {Girolama Alessandra}",

year = "2022",

month = sep,

day = "30",

doi = "10.1136/jnnp-2022-329657",

language = "English",

volume = "93",

pages = "1306--1316",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

number = "12",

}

Landi, D, Bovis, F, Grimaldi, A, Annovazzi, PO, Bertolotto, A, Bianchi, A, Borriello, G, Brescia Morra, V, Bucello, S, Buscarinu, MC, Caleri, F, Capobianco, M, Capra, R, Cellerino, M, Centonze, D, Cerqua, R, Chisari, CG, Clerico, M, Cocco, E, Cola, G, Cordioli, C, Curti, E, D'Ambrosio, A, D'Amico, E, De Luca, G, Di Filippo, M, Di Lemme, S, Fantozzi, R, Ferraro, D, Ferraro, E, Gallo, A, Gasperini, C, Granella, F, Inglese, M, Lanzillo, R, Lorefice, L, Lus, G, Malucchi, S, Margoni, M, Mataluni, G, Mirabella, M, Moiola, L, Nicoletti, CG, Nociti, V, Patti, F, Pinardi, F, Portaccio, E, Pozzilli, C, Ragonese, P, Rasia, S, Salemi, G, Signoriello, E, Vitetta, F, Totaro, R, Sormani, MP, Amato, MP & Marfia, GA 2022, 'Exposure to natalizumab throughout pregnancy: effectiveness and safety in an Italian cohort of women with multiple sclerosis', Journal of Neurology, Neurosurgery and Psychiatry, vol. 93, no. 12, pp. 1306-1316. https://doi.org/10.1136/jnnp-2022-329657

TY - JOUR

T1 - Exposure to natalizumab throughout pregnancy

T2 - effectiveness and safety in an Italian cohort of women with multiple sclerosis

AU - Landi, Doriana

AU - Bovis, Francesca

AU - Grimaldi, Alfonso

AU - Annovazzi, Pietro Osvaldo

AU - Bertolotto, Antonio

AU - Bianchi, Alessia

AU - Borriello, Giovanna

AU - Brescia Morra, Vincenzo

AU - Bucello, Sebastiano

AU - Buscarinu, Maria Chiara

AU - Caleri, Francesca

AU - Capobianco, Marco

AU - Capra, Ruggero

AU - Cellerino, Maria

AU - Centonze, Diego

AU - Cerqua, Raffaella

AU - Chisari, Clara Grazia

AU - Clerico, Marinella

AU - Cocco, Eleonora

AU - Cola, Gaia

AU - Cordioli, Cinzia

AU - Curti, Erica

AU - D'Ambrosio, Alessandro

AU - D'Amico, Emanuele

AU - De Luca, Giovanna

AU - Di Filippo, Massimiliano

AU - Di Lemme, Sonia

AU - Fantozzi, Roberta

AU - Ferraro, Diana

AU - Ferraro, Elisabetta

AU - Gallo, Antonio

AU - Gasperini, Claudio

AU - Granella, Franco

AU - Inglese, Matilde

AU - Lanzillo, Roberta

AU - Lorefice, Lorena

AU - Lus, Giacomo

AU - Malucchi, Simona

AU - Margoni, Monica

AU - Mataluni, Giorgia

AU - Mirabella, Massimiliano

AU - Moiola, Lucia

AU - Nicoletti, Carolina Gabri

AU - Nociti, Viviana

AU - Patti, Francesco

AU - Pinardi, Federica

AU - Portaccio, Emilio

AU - Pozzilli, Carlo

AU - Ragonese, Paolo

AU - Rasia, Sarah

AU - Salemi, Giuseppe

AU - Signoriello, Elisabetta

AU - Vitetta, Francesca

AU - Totaro, Rocco

AU - Sormani, Maria Pia

AU - Amato, Maria Pia

AU - Marfia, Girolama Alessandra

PY - 2022/9/30

Y1 - 2022/9/30

N2 - 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.

AB - 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.

KW - MRI

KW - multiple sclerosis

KW - obstetrics

UR - http://www.scopus.com/inward/record.url?scp=85141595997&partnerID=8YFLogxK

U2 - 10.1136/jnnp-2022-329657

DO - 10.1136/jnnp-2022-329657

M3 - Article

C2 - 36180219

AN - SCOPUS:85141595997

SN - 0022-3050

VL - 93

SP - 1306

EP - 1316

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 12

ER -

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

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