Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator approved as a single disease-modifying therapy (DMT) for highly active relapsing remitting multiple sclerosis (MS) in patients who meet specific clinical criteria.
Preclinical animal studies using fingolimod dosages of less than or equivalent to the human therapeutic dose have demonstrated increased rates of cardiac defects in the offspring and embryo/fetal death following administration to pregnant rats.
Human pregnancy exposure data are available for more than 1,350 fingolimod-exposed pregnancies. However, the evidence base remains limited as it predominantly consists of uncontrolled studies where fingolimod was discontinued in early pregnancy in the majority of cases.
Higher than expected rates of malformation have been described in some uncontrolled studies, and the manufacturer states that first trimester fingolimod exposure may be associated with a two-fold increased risk of malformation. However, supportive evidence of this effect is considered weak. Furthermore, available data from methodologically robust controlled studies are highly limited; therefore it is not currently possible to exclude an increased risk of malformation following first trimester fingolimod exposure.
The available evidence, although limited, does not currently identify increased risks of miscarriage, intrauterine fetal death, or preterm delivery following fingolimod exposure in early pregnancy. However, there is no evidence regarding the risk of preterm delivery or intrauterine fetal death following exposure in the later stages of pregnancy. A small number of case reports describe small for gestational age and infant neurodevelopmental impairment following maternal fingolimod use in early pregnancy. However, the lack of a control group prevents a meaningful assessment of the risk of these outcomes.
Owing to the possible increased risk of malformation, the manufacturers of fingolimod recommend that women should avoid pregnancy for two months after discontinuing therapy and that fingolimod should be discontinued in all patients who become pregnant. However, several studies have described MS relapse during pregnancy among women who discontinued fingolimod, either prior to conception or in early pregnancy. Close monitoring of the maternal condition is recommended where fingolimod is discontinued.
Detailed anomaly scans are recommended following first trimester fingolimod exposure. The anomalies which have been most commonly described in the literature include cardiac, renal and musculoskeletal anomalies. Exposure to fingolimod in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.