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For many women with rheumatic disease, pregnancy is safer when she takes pregnancy-compatible medications.  Use the guidance from the ACR Reproductive Health Guidelines included in the Discussion Guides to make informed decisions with your patients about medications in pregnancy. 

A female doctor in a white coat, with back turned to camera, sits at a table in a doctor's office or clinic with a smiling pregnant woman who sits with one hand cradling her belly, the other resting at her chin.
A high-angle photo, looking down at a pregnant woman dressed in jeans, t-shirt and sweater. She is holding and looking at a handful of yellow and whie pills. She holds a glass of water in the other hand.
Photo of an couple sitting together holding hand on the pregnant woman's belly

Pregnancy Compatible Medications – Strongly Recommended

The following medications are strongly recommended for use in pregnancy:

  • Azathioprine
  • Certolizumab
  • Colchicine
  • Hydroxychloroquine
  • Low-dose aspirin
  • Prednisone (use sparingly)
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Pregnancy Compatible Medications- Conditionally Recommended

These medications are considered safe in pregnancy with the included guidance:

  • Cyclosporin/Tacrolimus: monitor blood pressure
  • Infliximab, Etanercept, Golimumab, Adalimumab: discontinue several half-lives prior to delivery
  • Rituximab: only in very active rheumatic disease

Following the publication of the ACR Reproductive Health Guidelines in 2020, the FDA issued a Black Box Warning against the use of NSAIDs in pregnancy.

  • NSAIDs (Meloxicam, Ibuprofen, Naproxen, etc.): consult with obstetrician before use in pregnancy
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Insufficient Information for Use in Pregnancy

The following medications have insufficient information available about their safety for use in pregnancy:

Biologics

  • Abatacept
  • Anakinra
  • Apremilast
  • Avacopan
  • Secukinumab
  • Ustekinumab
  • Tocilizumab

Small-Molecule Drugs

  • Baricitinib
  • Tofacitinib
  • Upadacitanib
  • any other newly approved biologics
  • and other new approved small molecule medications
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Medications that Are Incompatible with Pegnancy

The following medications should be avoided during pregnancy:

  • Cyclophosphamide
  • Methotrexate
  • Mycophenolate Mofetil
  • Thalidomide
  • Lenalidomide
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Biologic Medications in Pregnancy

Most biologic medications are IgG1 antibodies, which are the primary antibodies that cross the placenta. They do not cross, however, until about 16 weeks gestation. This likely prevents biologic medications from crossing the placenta during the first trimester, which is when organogenesis takes place and most birth defects occur.  IgG1 antibodies cross at increasing levels as the pregnancy nears term. The baby, on the day of birth, has 60% higher concentrations of maternal antibodies than the mother. Therefore, for biologic medications that are IgG1 antibodies, the baby is likely to have MORE of the drug at birth than the mother.

A line graph showing the degree of fetal/infant exposure to a biologic medication taken by the mother. In the first trimester, there is no exposure. The curve rises during the second trimester, when there is limited exposure, and then rises more steeply during the third trimester, during which there is high exposure, peaking at delivery. After delivery, levels of biologic medication in the infant decrease slowly during the first months of life, and are not conveyed through the mother's breastmilk.

When and whether to hold biologic medications prior to delivery is up for debate!  The ACR Reproductive Health Guidelines recommend holding the TNF-inhibitors that are antibodies (adalimumab, etanercept, infliximab, and golimumab) several half-lives prior to delivery, so around 30-34 weeks gestation.  In Europe, many experts recommend holding biologic medications earlier to ensure the baby is born without any of the medication.  For women that would suffer significant harm from holding a biologic for several doses, for example a woman with severe inflammatory bowel disease, it may be reasonable to continue the drug through delivery (Mahadevan 2019).   

Certolizumab is pegylated and is not a full antibody.  By not containing an Fc portion, it cannot be transferred across the placenta. Babies exposed to certolizumab near delivery have undetectable or extremely low levels of certolizumab at birth (Mariette 2017).  Therefore, the ACR Reproductive Guidelines strongly recommend use of certolizumab throughout pregnancy.

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