Author response to Proschmann et al. & Sotgiu et al.
EmilioPortaccio, Neurologist, IRCCS Don Gnocchi Foundation (Florence, Italy)
Maria PiaAmato, Full Professor of Neurology, Department of NEUROFARBA, University of Florence (Florence, Italy)
Submitted July 19, 2018
We thank Proschmann et al. and Sotgiu et al. for their interest in our work and article. [1]
To respond to the valuable comments of Proschmann et al, our studies provided information on fetal and maternal risks after natalizumab exposure up to 12 weeks of gestation. [1-2] We found that avoiding drug washout before pregnancy and restarting natalizumab early after delivery significantly reduced the risk of disease reactivation during and after delivery. Of course, this approach did not completely prevent the risk of disease activity; we agree that the decision must be discussed individually with the mother, and that further investigation on this topic is needed. Indeed, data on safety of natalizumab continuation during the whole pregnancy are still limited and hematologic abnormalities have been reported after natalizumab exposure in the third trimester of gestation. Waiting for further information and following a more cautious approach, natalizumab can be stopped in the third trimester and restarted immediately after delivery. Drug continuation during the whole pregnancy could be limited to women with very active disease, again after a thorough discussion with the patient on possible and mainly unknown fetal risks.
Sotgiu et al. provide insightful comments on our study. [1] They report an additional case of 5-year-old dizygotic twins with severe autism spectrum disorder after exposure to natalizumab for nearly 8 weeks of gestation. They also provide possible explanations for natalizumab-related fetal toxicity. However, a relationship between autism spectrum disorder and maternal autoimmune disease should be taken into account. [3] Available evidence is not indicative of clear fetal harms after in-utero natalizumab exposure. As for congenital anomalies and developmental abnormalities, our study observed rates were within the estimates for the general population. Nevertheless, we are aware that available studies are underpowered to draw firm conclusions for rare events, such as congenital anomalies and developmental abnormalities, and we do agree that further surveillance is needed, expanding the observation to the developmental years of children. To this purpose, implementation of specific registries for pediatric monitoring after in-utero exposure to natalizumab and other disease modifying drugs would be advisable.
Portaccio E, Moiola L, Martinelle V, et al. Pregnancy decision-making in women with multiple slcerosis treated with natalizumab: I: Fetal risks. Neurology 2018; 90:e823-e831.
Portaccio E, Moiola L, Martinelle V, et al. Pregnancy decision-making in women with multiple slcerosis treated with natalizumab: II: Maternal risks. Neurology 2018; 90:e832-e839.
Chen SW, Zhong XS, Jiang LN, et al. Maternal autoimmune diseases and the risk of autism spectrum disorders in offspring: A systematic review and meta-analysis. Behav Brain Res 2016;296:61-69.
We thank Proschmann et al. and Sotgiu et al. for their interest in our work and article. [1]
To respond to the valuable comments of Proschmann et al, our studies provided information on fetal and maternal risks after natalizumab exposure up to 12 weeks of gestation. [1-2] We found that avoiding drug washout before pregnancy and restarting natalizumab early after delivery significantly reduced the risk of disease reactivation during and after delivery. Of course, this approach did not completely prevent the risk of disease activity; we agree that the decision must be discussed individually with the mother, and that further investigation on this topic is needed. Indeed, data on safety of natalizumab continuation during the whole pregnancy are still limited and hematologic abnormalities have been reported after natalizumab exposure in the third trimester of gestation. Waiting for further information and following a more cautious approach, natalizumab can be stopped in the third trimester and restarted immediately after delivery. Drug continuation during the whole pregnancy could be limited to women with very active disease, again after a thorough discussion with the patient on possible and mainly unknown fetal risks.
Sotgiu et al. provide insightful comments on our study. [1] They report an additional case of 5-year-old dizygotic twins with severe autism spectrum disorder after exposure to natalizumab for nearly 8 weeks of gestation. They also provide possible explanations for natalizumab-related fetal toxicity. However, a relationship between autism spectrum disorder and maternal autoimmune disease should be taken into account. [3] Available evidence is not indicative of clear fetal harms after in-utero natalizumab exposure. As for congenital anomalies and developmental abnormalities, our study observed rates were within the estimates for the general population. Nevertheless, we are aware that available studies are underpowered to draw firm conclusions for rare events, such as congenital anomalies and developmental abnormalities, and we do agree that further surveillance is needed, expanding the observation to the developmental years of children. To this purpose, implementation of specific registries for pediatric monitoring after in-utero exposure to natalizumab and other disease modifying drugs would be advisable.
For disclosures, please contact the editorial office at journal@neurology.org.