Emilio Portaccio1, Lucia Moiola2, Vittorio Martinelli2, Pietro Annovazzi2, Angelo Ghezzi2, Mauro Zaffaroni2, 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, Claudio Solaro2, Antonio Uccelli2, Alice Laroni2, Luisa Pastò2, Marta Giannini2, Maria Trojano2, Giancarlo Comi2, Maria Pia Amato2. 1. From IRCCS Don Gnocchi Foundation (E.P.), Florence; Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); 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 (C.S.), ASL3 Genovese; 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; Scientific Institute University Vita-Salute San Raffaele (L.M., V.M., G.C.), Milan; Multiple Sclerosis Study Center (P.A., A.G., M.Z.), ASST Valle Olona, Gallarate Hospital (VA); 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 (C.S.), ASL3 Genovese; 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 the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS). 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 through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models. RESULTS: A total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a postpartum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab (p < 0.001). In multivariable analysis, longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy (p = 0.001). Relapses in the postpartum year were related to relapses during pregnancy (p = 0.019) and early reintroduction of disease-modifying drugs (DMD; p = 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD (p = 0.024). CONCLUSIONS: Taken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible fetal risks that need to be discussed with the mother and require further investigation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in women with MS, the risk of relapses during pregnancy is higher in those who had been using natalizumab as compared to those who had been using interferon-β or no treatment.
OBJECTIVE: To assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis (MS). 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 through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models. RESULTS: A total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a postpartum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab (p < 0.001). In multivariable analysis, longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy (p = 0.001). Relapses in the postpartum year were related to relapses during pregnancy (p = 0.019) and early reintroduction of disease-modifying drugs (DMD; p = 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD (p = 0.024). CONCLUSIONS: Taken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible fetal risks that need to be discussed with the mother and require further investigation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in women with MS, the risk of relapses during pregnancy is higher in those who had been using natalizumab as compared to those who had been using interferon-β or no treatment.
Authors: Vilija G Jokubaitis; Olga Skibina; Raed Alroughani; Ayse Altintas; Helmut Butzkueven; Sara Eichau; Yara Fragoso; Kerstin Hellwig; Stella E Hughes; Louise Rath; Anneke van der Walt; Orla Gray Journal: Ther Adv Neurol Disord Date: 2021-04-12 Impact factor: 6.570
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
Authors: Georgina Arrambide; Ellen Iacobaeus; Maria Pia Amato; Tobias Derfuss; Sandra Vukusic; Bernhard Hemmer; Lou Brundin; Mar Tintore Journal: Mult Scler Date: 2020-06-12 Impact factor: 6.312