Re: Covid-19 treatments and vaccines must be evaluated in pregnancy
Abbas-Hanif and colleagues highlight the lack of trial data for Covid 19 treatments and vaccines in pregnancy . Their interesting and thought-provoking editorial has much wider implications for drug development as a whole – most clinical trials normally exclude pregnant women based on possible risks to the mother and baby.
As a clinician who worked for many years in a hospital respiratory clinic, I was often left to make a judgement call when prescribing medicines for pregnant patients. There is always some data available, based on considering the mechanism of action of the drug class, animal reproductive toxicology data and ( often uncontrolled ) case reports, but this is hardly comprehensive. SPCs usually advise prescribing “ if the expected benefit to the mother is greater than any possible risk to the foetus”.
The authors suggest that monoclonal antibodies are likely to be strong therapeutic candidates for use during pregnancy among people with target conditions, due to minimal off-target activity and limited placental transfer. Out of five monoclonal antibodies now licensed in the UK for severe asthma, only one ( omalizumab ) has a positive recommendation in pregnancy (If clinically needed, the use of Xolair may be considered during pregnancy) , since the data is lacking from the other newer drugs.
Furthermore, changes in maternal physiology during pregnancy may require different dosing, thus producing another unknown factor. Changes in drug systemic exposure during pregnancy could increase risks for mother and baby. Underexposure may lead to loss of efficacy and reduced control of maternal health with associated risks for foetal development, whereas overexposure could result in exposing the mother and the foetus to unnecessarily high doses, increasing the risk of adverse effects .
I fully support the suggestions to include pregnant and breastfeeding women in clinical trials to obtain the necessary data for these populations. It is clearly a large unmet need. Improving the quality of linked pregnancy registries and post-marketing spontaneous reports of drug usage in pregnancy would seem a sensible first step. Pharmaceutical companies are active in trying to collect robust data post-authorisation.
A blanket “Maternity Investigation Plan “for all new drugs may be more coercive than encouraging and a One Size fits all policy may be inappropriate; the PIPs have been a success, but not without some challenges.
There is a pressing need to change the way we approach medicines in pregnancy and breastfeeding. We need to move from systematic exclusion to inclusion of pregnant and breastfeeding women in clinical trials to obtain the necessary data for these populations, when it is considered safe to do so.
However, I would urge a cautious and sensitive approach - working with care and consideration for potential risk and benefits is paramount. Often, the longer-term effects of in utero exposure remain unknown and public confidence, as we have seen only too readily during this pandemic, is very quickly lost and very slow to be regained.
1. Allyah Abbas-Hanif, Neena Modi et al. Covid-19 treatments and vaccines must be evaluated in pregnancy BMJ 2021; 375 doi: https://doi.org/10.1136/bmj.n2377 (Published 14 October 2021)
2. Xolair Summary of Product Characteristics 4.6 Fertility, pregnancy and lactation https://www.medicines.org.uk/emc/product/5327/smpc
3. Cole S, Coppola P, Kerwash E et al. . Pharmacokinetic characterization to enable medicine use in pregnancy, the potential role of physiologically-based pharmacokinetic modeling: a regulatory perspective. CPT Pharmacometrics Syst Pharmacol2020;9:547-9. doi:10.1002/psp4.12551 pmid:32741152
Competing interests: I have worked in clinical practice ( Primary and Secondary Care ) and the pharmaceutical industry