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Natalizumab Throughout Pregnancy Lowers Postpartum Relapse Risk but Increases Risk of Neonatal Hematological Abnormalities
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Using a sample of 350 pregnancies, the maintenance of natalizumab during pregnancy past the 30th week had both positive and negative impacts, suggesting a risk-benefit discussion may be needed before patients begin treatment.
Kerstin Hellwig
A recently published observational cohort study of pregnant women with multiple sclerosis (MS) showed that continuing natalizumab (Tysabri; Biogen) during pregnancy after the 30th gestational week (gw) decreases the relapse risk postpartum; however, increases the risk for hematological abnormalities (HA) in the newborns. Published in Neurology, Neurosurgery, and Psychiatry, the study highlights the need for a risk-benefit discussion between neurologists and women as well as continued research assessing cohorts breastfeeding under monoclonal antibodies.
The study featured 350 natalizumab exposed pregnancies from the German Multiple Sclerosis and Pregnancy Registry who either discontinued natalizumab during the first trimester (n = 179; median exposure, 2.60 gw) and those who maintained treatment through gw 30 (n = 171; median exposure, 26.9 gw). All told, relapses that occurred during pregnancy and postpartum were found in 25.7% of those in the maintaining-group vs 62.6% of those in the 1st trimester group (P <.001).
Led by senior investigator Kerstin Hellwig, a neurologist at Katholisches Klinikum Bochum Sankt Josef-Hospital, Bochum, Nordrhein-Westfalen, Germany, the study aimed to analyze clinical disease activity during pregnancy and up to 1-year postpartum, and neonatal outcomes in newborns of mothers exposed to natalizumab throughout pregnancy. Between the 2 groups, results showed that neonatal outcomes were similar, and that natalizumab exposure after the first trimester, nor the dosing scheme, had a statistically significant impact on any neonatal outcome.
Of the 121 neonates in the maintaining group that had blood cell counts immediately after birth, 61.2% (n = 74) were born with HA, mainly with anemia (36.8%; n = 42) or thrombocytopenia (n = 36.8%). In comparison, no cases of HA were observed among the 5 neonates with first trimester exposure and available blood cell count. Among neonates with HA with at least 1 follow-up blood cell count (n = 30) from the maintaining group, only 23.3% (n = 7) of cases were reversible after a median of 2 days.
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In the adjusted logistic regression model, having a later timing of last natalizumab infusion during pregnancy was statistically significant associated with fewer pregnancy (OR, 0.93; 95% CI, 0.90-0.96) and postpartum relapses (OR, 0.97; 0.95-0.99). In addition, this led to fewer disability progression (OR, 0.94; 95% CI, 0.90-0.97) and reaching the Severe Relapse Disability Composite Score (SRDCS) during pregnancy (OR, 0.85; 95% CI, 0.71-0.93) while having an extended dosing interval did not.
Additional data showed that an early restart of natalizumab during the first 28 days postpartum was associated with a lowered risk of relapse (OR, 0.26; 95% CI, 0.13-0.50), whereas breast feeding was not (OR, 1.24; 95% CI, 0.62-2.44). Besides the known predictors of negative pregnancy outcomes, such as maternal body mass index, tobacco and alcohol consumption, the use of high-dose glucocorticosteroid treatment during pregnancy was statistically significantly associated with preterm birth (OR, 9.43; 95% CI, 3.07-30.8) but not with lower mean births weight (β −23, 95% CI: −181–136) or small for gestational age (OR: 0.59, 95% CI: 0.19 to 1.55).
"Strengths of this study include a high enrolment rate during the first trimester of pregnancy, resulting in reliable, robust and prospective long-term data of high-quality, along with a large sample size and including a control group," the study authors wrote. "By measuring the fetal HA risk in the majority of our cohort on the one hand and the maternal disability risk on the other hand, this study provides important information and supports decision-making for women with highly-active MS and their treating clinicians in the field of pregnancy planning."
