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

J Neurol Neurosurg Psychiatry. 2022 Sep 30:jnnp-2022-329657. doi: 10.1136/jnnp-2022-329657. Online ahead of print.

Authors

Doriana Landi¹, Francesca Bovis², Alfonso Grimaldi³, Pietro Osvaldo Annovazzi⁴, Antonio Bertolotto⁵, Alessia Bianchi⁶, Giovanna Borriello⁷, Vincenzo Brescia Morra⁸, Sebastiano Bucello⁹, Maria Chiara Buscarinu¹⁰, Francesca Caleri¹¹, Marco Capobianco⁵, Ruggero Capra¹², Maria Cellerino¹³, Diego Centonze^{14

15}, Raffaella Cerqua¹⁶, Clara Grazia Chisari¹⁷, Marinella Clerico¹⁸, Eleonora Cocco¹⁹, Gaia Cola³, Cinzia Cordioli¹², Erica Curti²⁰, Alessandro d'Ambrosio²¹, Emanuele D'Amico¹⁷, Giovanna De Luca²², Massimiliano Di Filippo²³, Sonia Di Lemme¹⁵, Roberta Fantozzi¹⁵, Diana Ferraro²⁴, Elisabetta Ferraro²⁵, Antonio Gallo²¹, Claudio Gasperini²⁶, Franco Granella²⁰, Matilde Inglese^{13

27}, Roberta Lanzillo⁸, Lorena Lorefice²⁸, Giacomo Lus²⁹, Simona Malucchi⁵, Monica Margoni³⁰, Giorgia Mataluni³, Massimiliano Mirabella³¹, Lucia Moiola³², Carolina Gabri Nicoletti³, Viviana Nociti³¹, Francesco Patti¹⁷, Federica Pinardi³³, Emilio Portaccio³⁴, Carlo Pozzilli³⁵, Paolo Ragonese⁶, Sarah Rasia¹², Giuseppe Salemi⁶, Elisabetta Signoriello²⁹, Francesca Vitetta³⁶, Rocco Totaro³⁷, Maria Pia Sormani², Maria Pia Amato^{34

38}, Girolama Alessandra Marfia³

Affiliations

¹ Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy [email protected].
² Department of Health Sciences, Section of Biostatistics, University of Genova, Genoa, Italy.
³ Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Roma, Italy.
⁴ Multiple Sclerosis Center, Neurology II Unit, ASST Valle Olona, Gallarate Hospital, Gallarate, Italy.
⁵ Multiple Sclerosis Center (CRESM), Department of Neurology, 'San Luigi Gonzaga' University Hospital, Orbassano, Italy.
⁶ Unit of Neurology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, Palermo University, Palermo, Italy.
⁷ Multiple Sclerosis Center, 'S. Andrea' Hospital, Sapienza University of Rome, Rome, Italy.
⁸ Department of Neurosciences Reproductive Sciences and Odontostomatology, Multiple Sclerosis Center, Federico II University, Naples, Italy.
⁹ Multiple Sclerosis Center, "E. Muscatello" Hospital - ASP8, Augusta (SR), Italy.
¹⁰ Department of Neuroscience, Mental Health and Sensory Organs, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
¹¹ Multiple Sclerosis Center, Department of Neurology, 'F. Tappeiner' Hospital, Merano (BZ), Italy.
¹² Multiple Sclerosis Center, Spedali Civili of Brescia, Montichiari (BS), Italy.
¹³ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genova, Italy.
¹⁴ Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
¹⁵ Unit of Neurology, IRCCS Neuromed, Pozzilli (IS), Italy.
¹⁶ Neurological Clinic, Department of Experimental and Clinical Medicine, Ospedali Riuniti, Ancona, Italy.
¹⁷ Department of Medical and Surgical Sciences and Advanced Technologies 'G.F. Ingrassia', Section of Neurosciences, University of Catania, Catania, Italy.
¹⁸ Clinical and Biological Sciences Department, Neurology Unit, University of Torino, 'San Luigi Gonzaga' Hospital, Orbassano, Italy.
¹⁹ Multiple Sclerosis Center, Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy.
²⁰ Unit of Neurology, Department of General and Specialized Medicine, Parma University Hospital, Parma, Italy.
²¹ I Division of Neurology, Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Napoli, Italy.
²² Multiple Sclerosis Center, 'SS Annunziata' Hospital, 'Gabriele d'Annunzio' University Chieti-Pesacara, Chieti, Italy.
²³ Section of Neurology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
²⁴ Department of Biomedical Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
²⁵ Neurology Unit, Presidio Ospedaliero 'San Filippo Neri', Roma, Italy.
²⁶ Department of Neurosciences, 'San Camillo Forlanini' Hospital, Rome, Italy.
²⁷ Department of Neurology, Policlinico 'San Martino Hospital'-Sistema Sanitario Regione, Genoa, Italy.
²⁸ Multiple Sclerosis Centre, Binaghi Hospital, ATS Sardegna-Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
²⁹ Department of Advanced Medical and Surgical Sciences, II Division of Neurology, Multiple Sclerosis Center, University of Campania 'L. Vanvitelli', Naples, Italy.
³⁰ Multiple Sclerosis Center of the Veneto Region, Department of Neurosciences, University of Padua, Padua, Italy.
³¹ Department of Neurosciences, Centro di Ricerca Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, Rome, Italy, 'A.Gemelli' University Hospital, Rome, Italy.
³² Multiple Sclerosis Center, Neurology Department, San Raffaele Hospital IRCCS, Milan, Italy.
³³ UOSI Multiple Sclerosis Rehabilitation, IRCCS Istituto delle scienze neurologiche, Bologna, Italy.
³⁴ Division Neurological Rehabilitation, Department of NEUROFARBA, University of Florence, Florence, Italy.
³⁵ Multiple Sclerosis Center, Department of Human Neurosciences, 'S.Andrea' Hospital, Sapienza University of Rome, Rome, Italy.
³⁶ Neurology Unit, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
³⁷ Demyelinating Disease Center, Neurology Unit, University of L'Aquila, L'Aquila, Italy.
³⁸ IRCCS, Fondazione Don Carlo Gnocchi, Florence, Italy.

PMID: 36180219
DOI: 10.1136/jnnp-2022-329657

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.