In late September 2019, the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended a change in the authorization of Interferon-beta therapy during pregnancy and lactation. Although this is actually very important information, I have not yet commented on this change here – probably because we have already had a rather permissive approach to interferons in fertility treatment in practice – but now it is official and of course this is good and practical news. What exactly happened – or on what basis is the changed recommendation based? Since MS often occurs in women of childbearing age and information on the effects of the drugs at the time of market introduction is only available to a limited extent, a prospective European IFN beta pregnancy registry was established in the past. The data from this register and the data from the health registers of Finland and Sweden have now been evaluated with regard to pregnancy outcomes.
In total, the pregnancy outcomes of more than 900 pregnancies could be evaluated in the European Interferon beta pregnancy register. Most pregnancies (> 500) were exposed to Interferon-beta in the first trimester of pregnancy. The rates of ectopic pregnancies (tubal pregnancies), spontaneous abortions (miscarriages), stillbirths and live births with anomalies were examined. The rates of spontaneous abortion were 10.7%, which is well below the expected rate of up to 21%, which is described for the normal population. Also, the rate of birth anomalies was 1.8%, lower than the expected rate of 3 – 5% of pregnancies in the normal population. There were also no safety signals for the other evaluation parameters. The pregnancy outcomes of the European Register could also be more or less exactly confirmed by the evaluation of the Scandinavian registers.
Thus, both the European and the Scandinavian register data provided no evidence of a negative influence of an IFN beta exposure before conception and/or during pregnancy on the outcome of the pregnancy and the child. As a result, the use of all Interferon preparations during pregnancy can now be considered, if this should be clinically necessary.
As already mentioned above, we have already been practicing for some time – based on systematic reviews and registry studies that showed no adverse effects of an IFN therapy – not to discontinue interferons even before a planned pregnancy, but to do this only with the onset of pregnancy, especially with regard to the protection of the mother. This procedure is now official with the change of approval and can be considered safe – which is good news.
It is also good news that the change in approval also affects lactation. The new professional information of the Interferon-beta preparations also includes that Interferon-beta can be used during lactation. The question of using an interferon during lactation is frequently asked, as many women want to breastfeed their child, but do not want to give up adequate medication protection against MS attacks. Now the question can be clearly answered: Even officially, no harmful effects on the breastfed newborn/child are to be expected. The statement is based on studies that have shown that IFN beta does not significantly enter the milk compartment. In many milk samples, IFN beta was not detectable, and even using the highest measured value, the estimated relative infant dose was 0.006% of the maternal dose. No clinical side effects were observed in the breastfed infant in the studies. This will also be related to the fact that proteins such as interferon lose their effectiveness during passage through the gastrointestinal tract and thus a possible undesirable effect on the child is prevented by oral intake of interferon during breastfeeding (Hale TW et al. Breastfeed Med. 2012 Apr;7(2):123-5; Hellwig K, Gold R. J Neurol. 2011; 258(3): 502 – 3).
Overall, positive news for mother and child regarding the use of an interferon preparation in pregnancy and lactation – and therefore important to communicate this news here on MS-Docblog.
