Immunomodulatory drug use and reproductive health
Australian Rheumatology Association, 2022, 2022Flint, 2016
The choice of immunomodulatory drug for people of childbearing potential needs to be carefully considered to prevent pregnancy complications and other adverse outcomes—seek specialist advice. For many immunomodulatory drugs there is a paucity of data to inform treatment decisions. Shared decision making involving the patient, their treating specialist, general practitioner and, as necessary, other specialists (eg obstetric drug information service providers1) is crucial.
When immunomodulatory therapy is initiated for people of childbearing potential, consider the effect of the drug on long-term fertility (eg premature gonadal failure with cyclophosphamide), as well as the need for effective contraception (eg when a teratogenic drug is used).
For people who are planning pregnancy, choice of therapy should take into account the impact of the drug on fertility, the safety of the drug during pregnancy, as well as the need to implement measures that may reduce the risk of harms (eg folic acid supplementation for patients treated with sulfasalazine, therapeutic drug monitoring for patients treated with ciclosporin). The risks of immunomodulatory therapy to the fetus or infant must be balanced against the risks associated with poor disease control if therapy is discontinued. Ideally, these factors should be considered before pregnancy is planned to ensure that drug therapy can be continued throughout the perinatal period.
For people who are breastfeeding, consideration should be given to the compatibility of the drug with breastfeeding. Ideally, this should be considered before pregnancy is planned, to ensure that therapy can be continued throughout the perinatal period.
There are some data to suggest that the following drugs may, with appropriate precautions, be safely used in pregnancy: azathioprine, ciclosporin, hydroxychloroquine, prednisolone (or prednisone) and sulfasalazine. Tumour necrosis factor (TNF) inhibitors can also be used in pregnancy, but should be avoided in the third trimester because they cross the placenta into the fetal circulation and can impair the neonatal immune system. The exception is certolizumab pegol, which does not cross the placenta, and thus is safe throughout pregnancyMariette, 2018Sammaritano, 2020.
The Australian Rheumatology Association website provides detailed information on the use of immunomodulatory drugs in patients of childbearing potential (including males) or pregnant or breastfeeding people. Guidelines are also available from the British Society for Rheumatology and British Health Professionals in Rheumatology2. Advice for drug compatibility with pregnancy and breastfeeding is accessible through icons in drug recommendations. However, note that it is not intended that the Therapeutic Goods Administration (TGA) pregnancy category would be the sole basis of decision making in the use of a drug during pregnancy, in part because it does not provide information about the balance of harms and benefits in a particular patient. Furthermore, the category does not indicate the stages of fetal development that might be affected by drug exposure and may not reflect the most up-to-date information about the drug’s use in pregnancy.