Emilio Portaccio1, Pietro Annovazzi2, Angelo Ghezzi2, Mauro Zaffaroni2, Lucia Moiola2, Vittorio Martinelli2, Roberta Lanzillo2, Vincenzo Brescia Morra2, Francesca Rinaldi2, Paolo Gallo2, Carla Tortorella2, Damiano Paolicelli2, Carlo Pozzilli2, Laura De Giglio2, Paola Cavalla2, Eleonora Cocco2, Maria Giovanna Marrosu2, Francesco Patti2, Claudio Solaro2, Paolo Bellantonio2, Antonio Uccelli2, Alice Laroni2, Luisa Pastò2, Marta Giannini2, Maria Trojano2, Giancarlo Comi2, Maria Pia Amato2. 1. From IRCCS Don Gnocchi Foundation (E.P.), Florence; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Department of Neurosciences, Reproductive and Odontostomatological Sciences (R.L., V.B.M.), Federico II University of Naples; Department of Neurosciences (F.R., P.G.), Multiple Sclerosis Centre-Veneto Region (CeSMuV), University Hospital of Padova; Department of Neurology (C.T., D.P., M.T.), University of Bari; Department of Neurology and Psychiatry (C.P., L.D.G.), "La Sapienza" University, Rome; Department of Neurology (P.C.), University of Torino; Department of Medical Sciences and Public Health (E.C., M.G.M.), University of Cagliari; Department of Neurology (F.P.), University of Catania; Department of Neurology (C.S.), ASL3 Genovese; Multiple Sclerosis Center (P.B.), IRCCS Neuromed, Pozzilli; Department of Neurology (A.U., A.L.), University of Genova; and Department of NEUROFARBA (L.P., M.G., M.P.A.), University of Florence, Italy. portilio@tin.it. 2. From IRCCS Don Gnocchi Foundation (E.P.), Florence; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Department of Neurosciences, Reproductive and Odontostomatological Sciences (R.L., V.B.M.), Federico II University of Naples; Department of Neurosciences (F.R., P.G.), Multiple Sclerosis Centre-Veneto Region (CeSMuV), University Hospital of Padova; Department of Neurology (C.T., D.P., M.T.), University of Bari; Department of Neurology and Psychiatry (C.P., L.D.G.), "La Sapienza" University, Rome; Department of Neurology (P.C.), University of Torino; Department of Medical Sciences and Public Health (E.C., M.G.M.), University of Cagliari; Department of Neurology (F.P.), University of Catania; Department of Neurology (C.S.), ASL3 Genovese; Multiple Sclerosis Center (P.B.), IRCCS Neuromed, Pozzilli; Department of Neurology (A.U., A.L.), University of Genova; and Department of NEUROFARBA (L.P., M.G., M.P.A.), University of Florence, Italy.
Abstract
OBJECTIVE: To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA). METHODS: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed. RESULTS: A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9-8.5, p < 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies (p < 0.001). CONCLUSION: Our results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in women with MS, natalizumab exposure increases the risk of spontaneous abortion as compared to IFN-β-exposed or untreated patients (OR 3.9, 95% CI 1.9-8.5).
OBJECTIVE: To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA). METHODS: Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed. RESULTS: A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9-8.5, p < 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies (p < 0.001). CONCLUSION: Our results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in women with MS, natalizumab exposure increases the risk of spontaneous abortion as compared to IFN-β-exposed or untreated patients (OR 3.9, 95% CI 1.9-8.5).
Authors: Alessandra Carta; Ignazio R Zarbo; Chiara Scoppola; Giulia Pisuttu; Marta Conti; Maria C Melis; Federica De Martino; Antonella Serra; Maria A Biancu; Franca R Guerini; Riccardo Bazzardi; Stefano Sotgiu Journal: Mult Scler J Exp Transl Clin Date: 2021-05-28
Authors: Jihad S Inshasi; Sarmed Alfahad; Taoufik Alsaadi; Ali Hassan; Tayseer Zein; Victoria Ann Mifsud; Suzan Ibrahim Nouri; Mustafa Shakra; Ahmed Osman Shatila; Miklos Szolics; Mona Thakre; Ajit Kumar; Amir Boshra Journal: Neurol Ther Date: 2021-04-23
Authors: Michael Auer; Anne Zinganell; Harald Hegen; Gabriel Bsteh; Franziska Di Pauli; Klaus Berek; Elena Fava; Sebastian Wurth; Thomas Berger; Florian Deisenhammer Journal: Sci Rep Date: 2021-12-02 Impact factor: 4.379