Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden

Abstract

Background Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). Methods This cohort study used Finnish (1996–2014) and Swedish (2005–2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. Results Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31–0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06–2.78). Conclusion In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

Prevalence of adverse pregnancy outcomes after exposure to interferon beta prior to or during pregnancy in women with MS: Stratification by maternal and newborn characteristics in a register-based cohort study in Finland and Sweden

“…After stratification by newborn characteristics, our results were also consistent with the unstratified results in the same population [31], with no increased prevalence estimates among the exposed pregnancies. Although newborns born within 28-36 weeks of gestation had a numerically higher prevalence of MCAs and the composite serious adverse pregnancy outcomes in the IFN-beta exposed pregnancies, the result was based on few outcomes per stratum and the precision of the prevalence was low.…”

“…Our result indicated that the descriptive prevalence of serious and other adverse pregnancy outcomes was not increased among pregnancies exposed to IFN-beta in the strata of maternal characteristics, which is consistent with the unstratified results in the same population [19,31]. The finding that in some strata the prevalence appeared decreased among the pregnancies exposed only to IFN-beta compared to pregnancies unexposed to any MSDMDs, without statistical significance, may have been caused by underlying factors that were unfavourable among the unexposed women and that this study using the available register data could not detect (e.g., life-style factors (beyond BMI), maternal alcohol and substance use, or actual use of teratogenic drugs before and during pregnancy).…”

“…The stratified analysis results of this large cohort study mirror the unstratified findings in the same population [19,31], that IFN-beta exposure before or during pregnancy does not appear to be harmful for the child. Thus, this study provides additional evidence on the safety of prescribing IFN-beta treatment for women with MS who are planning pregnancy, until the pregnancy is confirmed or even beyond, if the risk of relapse and disability accumulation during pregnancy needs to be reduced.…”

“…Additional confounder adjusted post hoc analyses further investigated whether the effect of IFN-beta exposure is modified by maternal characteristics, as detailed in Appendix A.6. The analyses were considered for the most prevalent outcomes if effect modification was suspected due to differing pattern of point prevalences for an adverse pregnancy outcome among the exposed and unexposed, when comparing the results in strata of a maternal characteristic to the unstratified results [31].…”

“…Thus, this study provides additional evidence on the safety of prescribing IFN-beta treatment for women with MS who are planning pregnancy, until the pregnancy is confirmed or even beyond, if the risk of relapse and disability accumulation during pregnancy needs to be reduced. The findings of this PASS cohort [19,31] also led to a label change in the European Union, according to which IFN-beta products may now be considered during pregnancy, if clinically needed.…”