Table 1:

Biologic Disease-Modifying Antirheumatic Drugs in Pregnancy

Drug	Mechanism of Action	Rheumatologic uses	Pregnancy Category	Data Available	Placental Transfer	Lactation
Abatacept 2,78,79	Selective T cell co-stimulation modulator	• rheumatoid arthritis • juvenile idiopathic arthritis • psoriatic arthritis	C	• No increased risk in animal studies when exposed to maximum recommended human dose. • At extremely elevated doses there were alterations in immune function. • Recommended to discontinue 10 weeks prior to conception • A case series of 152 patients resulted in increased rates of miscarriage and congenital malformations when used in combination with MTX • Registry for monitoring use in pregnancy (1–877-311–8972)	• Crosses the placenta but animal studies have not revealed congenital abnormalities	• Unknown if secreted in breast milk; therefore, considered contraindicated
Adalimumab 2,3,7	TNF inhibitor	• Rheumatoid arthritis • Juvenile idiopathic arthritis • Ankylosing spondylitis • Psoriatic arthritis	B	• No increased rate of miscarriages or congenital malformations when used during first trimester. • Placental transfer during 2nd and 3rd trimester • If continued in the 3rd trimester, the result is therapeutic levels in the newborn’s cord blood.	• Greatest during 3rd trimester • IgG1 molecules are actively transported from maternal circulation to the fetal circulation via binding to the neonatal Fc receptor. • Binding affinity to the neonatal Fc receptor is highest for complete monoclonal antibodies.	• Presence detected at 0.1% to 1%, no effect on milk production or adverse effects
Apremilast 28	Phospodiesterasae-4 inhibitor	• Psoriatic arthritis	C	• Dose related abortions have been reported in animal studies	• Rate of placental transfer is unknown	• Presence in breast milk is unknown but cannot be excluded
Anakinra 2,7,83	IL-1 inhibitor	• Rheumatoid arthritis • Cryopyrin associated periodic syndromes	B	• No harm was demonstrated in animal studies even at doses 25 times the maximum recommended human dose. • In one report of use during pregnancy, placenta retention was the only abnormality. • Limited data reported relating to safety if continued during pregnancy.	• Has been shown to pass through placenta.	• Due to limited data its use is not recommended.
Baricitinib 93	JAK inhibitor	• Rheumatoid arthritis	-	• High doses in animals resulted in reduced fetal body weights, increased embryo-lethality, and does related increases in skeletal malformations	• Unknown	• Present in animal breast milk but clinically relevance in humans is unknown
Belimumab 7,80,81	Reduces B-cell activity	• Systemic lupus erythematosus	C	• One case report demonstrated healthy pregnancy with mild Epstein’s anomaly in baby. • No evidence in animal models of embryotoxicity or fetal malformations with exposure 9 times the exposure at the maximum recommended human dose. • Registry for monitoring use prior to or during pregnancy (http://pregnancyregistry.gsk.com/belimumab.html or www.bprgsk.com)	• Actively transported across the placenta during the third trimester and may affect immune response in the in utero-exposed infant.	• No data; however, large protein molecule; therefore, absorption unlikely due to low bioavailability.
Canakinumab 84,85	IL-1 inhibitor	• Cryopyrin-associated periodic syndromes • Familial Mediterranean fever • Hyperimmune D syndrome • Mevalonate kinase deficiency • Tumor necrosis factor receptor associated periodic syndrome	C	• Fetal skeletal development delay in animal models at doses 23-fold the maximum recommended human dose and greater; there was no embryotoxicity or fetal malformations. • No human studies	• A case report in a patient with Muckle Wells Syndrome, demonstrated 2 times higher levels of canakinumab in the cord blood and neonatal blood indicating active placental transfer. The baby was delivered, and no congenital anomalies were identified.	• Unknown if secreted into breast milk.
Certolizumab 2,7	TNF inhibitor	• Ankylosing spondylitis • Axial spondyloarthritis • Psoriatic arthritis • Rheumatoid arthritis	B	• No increased rate of miscarriages or congenital malformations when used during first trimester. • Possible placental transfer during 2nd and 3rd trimester. • If continued in the 3rd trimester, the result is below detection to minimal levels of certolizumab can be found in the neonate’s cord blood.	• Greatest during 3rd trimester • IgG1 molecules are actively transported from maternal circulation to the fetal circulation via binding to the neonatal Fc receptor. • Binding affinity to the neonatal Fc receptor is absent with Certolizumab.	• Unknown if secreted into breast milk. • (see other TNF information)
Etanercept 2,7	TNF inhibitor	• Ankylosing spondylitis • Psoriatic arthritis • Rheumatoid arthritis • Juvenile idiopathic arthritis	B	• No increased rate of miscarriages or congenital malformations when used during first trimester. • Placental transfer during 2nd and 3rd trimester. • If continued in the 3rd trimester, the result is very low levels of etanercept can be found in the neonate’s cord blood.	• Greatest during 3rd trimester • IgG1 molecules are actively transported from maternal circulation to the fetal circulation via binding to the neonatal Fc receptor. • Binding affinity to the neonatal Fc receptor is low.	• Undetectable in one infant (12 weeks old), despite being present in the breast milk.
Golimumab 2,7	TNF inhibitor	• Ankylosing spondylitis • Psoriatic arthritis • Rheumatoid arthritis	B	• No increased rate of miscarriages or congenital malformations when used during first trimester. • Placental transfer during 2nd and 3rd trimester • If continued in the 3rd trimester, the result is therapeutic levels in the newborn’s cord blood.	• Greatest during 3rd trimester • IgG1 molecules are actively transported from maternal circulation to the fetal circulation via binding to the neonatal Fc receptor. • Binding affinity to the neonatal Fc receptor is highest for complete monoclonal antibodies.	• Unknown if secreted into breast milk. • (see other TNF information)
Infliximab 2,7	TNF inhibitor	• Ankylosing spondylitis • Psoriatic arthritis • Rheumatoid arthritis	B	• No increased rate of miscarriages or congenital malformations when used during first trimester. • Placental transfer during 2nd and 3rd trimester • If continued in the 3rd trimester, the result is therapeutic levels in the newborn’s cord blood.	• Greatest during 3rd trimester • IgG1 molecules are actively transported from maternal circulation to the fetal circulation via binding to the neonatal Fc receptor. • Binding affinity to the neonatal Fc receptor is highest for complete monoclonal antibodies.	• Undetectable in breast milk samples and serum of 3 infants.
Rilonacept 86	IL-1 inhibitor	• Cryopyrin Associated Periodic Syndromes	C	• Fetal harm occurred during animal studies at exposure that was below that expected clinically	• Unknown	• Unknown
Rituximab 2,7	Binds the CD20 antigen activating B-cell cytotoxicity	• Rheumatoid arthritis • Granulomatosis with polyangiitis	C	• Documented spontaneous and therapeutic abortions and premature births. • Congenital abnormalities have included a clubfoot, ventral septal defect, patent foramen ovale, and patent ductus arteriosus. • Hematologic abnormalities and increased risk of infection noted.	• Reduction of B cells has been noted in offspring. • Potentially increasing risk of infection and/or hematologic abnormalities.	• Unknown if secreted into breast milk.
Sarilumab 87	IL-6 inhibitor	• Rheumatoid arthritis	-	• In animal studies it was not embryotoxic or teratogenic with exposure up to 84 times the maximum recommended human dose and it did not impact growth or development up to one month after birth; however, sarilumab was detected in the serum of neonates. *Pregnancy exposure registry: 1–877-311–8972.	• Monoclonal antibodies are actively transported across the placenta during the 3rd trimester • Detected in animal neonate’s serum 1 month after birth	• Unknown if secreted into breast milk.
Secukinumab 91,92	IL-17 inhibitor	• Ankylosing spondylitis • Psoriatic arthritis	B	• No adverse development effects or embryo-fetal toxicity were observed in animals at doses 30 times those recommended in humans • Data from Novartis global safety database showed: 238 pregnancies, rates of spontaneous abortions were in line with established rates for this population; however, most patients stopped secukinumab during the 1st trimester	• Humanized monoclonal antibody with the majority of placental transfer during the 3rd trimester	• Unknown if excreted in breast milk.
Tocilizumab 79,88	IL-6 inhibitor	• Rheumatoid arthritis • Giant cell arteritis • Polyarticular JIA • Systemic JIA • Cytokine release syndrome	C	• No teratogenicity demonstrated in animal models at any dose. • Increased risk of abortion rates and fetal mortality at doses >100-fold the dose used in humans. *Pregnancy exposure registry: 1–877-311–8972.	• Monoclonal antibodies are transported across the placenta in a linear fashion, with the largest amount transferred during the 3rd trimester.	• Unknown if secreted into breast milk; however, IgG is excreted in human milk; therefore, it is expected that it could be present. Breastfeeding is not recommended while using this medication.
Tofacitinib 2,7,94	JAK inhibitor	• Psoriatic arthritis • Rheumatoid arthritis	C	• Teratogenicity and feticidal effect at much higher levels than the maximum recommended dose in humans have been reported in animal studies. *Pregnancy exposure registry: 1–877-311–8972.	---------	• No data but due to its low molecular weight passage into breast milk possible. Should not be used when breastfeeding.
Ustekinumab 7,89,90	IL-12/23 inhibitor	• Psoriatic arthritis	B	• Limited data but based on what is known there is no increased rate of miscarriage or congenital malformation in animal studies at doses 100 times the maximum recommended human dose. *Pregnancy exposure registry: 1–877-311–8972.	• Does not cross the placenta early in pregnancy but may cross later in pregnancy.	• No data; however, large protein molecule; therefore, absorption unlikely due to low bioavailability.