TABLE 3.
Guidelines for continuation of biological drugs in pregnancy, lactation and male partners.
| Biologic name | Outcomes of pregnancy animal studies a | ACR | EULAR | BSR/BHPR |
|---|---|---|---|---|
| Pregnancy/Breastfeeding/Paternal Sammaritano et al. (2020) | Pregnancy/Breastfeeding/Paternal Götestam Skorpen et al. (2016) | Pregnancy/Breastfeeding/Paternal Flint et al. (2016) | ||
| Infliximab | Infliximab analogue did not result in fetal malformations or developmental effects in mice offspring. | Conditional b /Continue/Continue | Stop at week 20/Continue/- | Stop at week 16/Continue/Continue |
| Adalimumab | Exposing cynomolgus monkeys to doses higher than the MHRD did not result in fetal malformations or harms. | Stop at week 20/Continue/- | Conditional b /Continue/Continue | |
| Golimumab | No neonatal or postnatal developmental harm with pregnancy and breastfeeding in monkeys. | Conditional b /NA/- | NA/NA/NA | |
| Etanercept | No evidence of mal-formations in rats and rabbits exposed to etanercept during embryogenesis. Normal post-natal development of rats exposed to doses 48 times the human dose. | Continue/Continue/- | Conditional b /Continue/Continue | |
| Certolizumab | Studies in rats using antimurine analogue resulted in no fetal harms or malformations | Continue/Continue/Continue | Continue/Continue/- | Continue/Continue/Continue |
| Abatacept | In-utero and juvenile exposure of rats to doses 11 times the MHRD resulted in disturbance in fetal immune response. | Discontinue/Conditional/NA | Discontinue c /Discontinue c /- | Discontinue/NA/NA |
| Rituximab | Animal exposure showed no teratogenic effect but decrease in B-cell lymphoid tissue and reversible decline in B-cell population. | Conditional d /Conditional d /Continue | Discontinue c /Discontinue c /- | Discontinue 6 mths pre-conception/NA/Continue |
| Belimumab | Exposure of monkeys throughout pregnancies to high doses resulted in no fetal malformations. Fetal decrease in peripheral and lymphoid tissue B-cell population, increase in total IgG and decrease in IgM were reported. All changes recovered within the first year of life. | Discontinue/Conditional e /NA | Discontinue c /Discontinue c /- | Discontinue/NA/NA |
| Secukinumab | No fetal toxicity or malformations on exposure to high doses. | Discontinue/Conditional e /NA | — | — |
| Secukinumab analogue did not lead to abnormal morphological or immunological effects In a pre- and post-natal developmental study. | ||||
| Ixekizumab | No fetal toxicity or malformations was observed on exposure to high doses | — | — | — |
| In pre and post-natal developmental studies, no abnormal morphological or immunological effects. However, early neonatal deaths were reported, unlikely due to ixekizumab. | ||||
| Ustekinumab | In embryofetal and developmental studies, exposure >100 times higher than the human SC exposure resulted in no fetal toxicities, malformations, developmental, morphological or immunological effects. Unexplained 2 neonatal deaths were reported. | Discontinue/Conditional e /NA | Discontinue c /Discontinue c /- | — |
| Tocilizumab | No fetal toxicity, malformations, developmental or immunological abnormalities were reported. | Discontinue/Conditional e /NA | Discontinue c /Discontinue c /- | Discontinue 3 mths pre-conception/NA/NA |
| Increase in rate of abortions was reported in monkeys at doses 1.25 higher than the MRHD. | ||||
| Anakinra | Studies on rabbits and mice at doses 25 times the MRHD resulted in no fetal harm. | Discontinue/Conditional e /Conditional | Discontinue c /Discontinue c /- | Discontinue/NA/NA |
| Canakinumab | Studies on monkeys at doses 11 times the MRHD showed no malformations. Rate of skeletal developmental delay due to incomplete ossification was increased. | — | — | — |
| Rilonacept | Study on monkeys reported rib and vertebral abnormalities. There was also increase in rate of stillbirths and neonatal deaths. | — | — | — |
| Eculizumab | Exposure of mice to doses up to 8 times the MRHD early in pregnancy resulted in no abnormality. Exposure during organogenesis resulted in 2/230 neonates with retinal dysplasia. Exposure from implantation to weaning was associated with higher death rate among pups. All live births showed normal development. | — | — | — |
| Denosumab | In monkeys, high still-birth and newborn mortality rates due to intrinsic fetal defects such as increased bone mass, insufficient hematopoiesis, hypoglycemia, and hypocalcemia. | — | — | — |
| Abnormal bone growth with decreased strength, absence of lymph-node groups, dental dysplasia and reduced neonatal growth were reported in the offspring. |
a
Animal experimental data were extracted from FDA labes of each drug.
b
Stop before third trimester.
c
Discontinue except if no pregnancy compatible alternative to control activity.
d
Consider use in organ/life threatening conditions.
e
Limited available data but expected minimal transfer in breast milk.
NA: No available recommendation due to limited published data. — Not mentioned in the guidelines. MHRD, maximum human recommended dose.