Rheumatoid Arthritis (RA) is an autoimmune condition causing painful joint inflammation, frequently affecting women of childbearing age. Managing this chronic disease requires controlling inflammation to prevent joint damage while minimizing risk to a developing fetus. Uncontrolled RA disease activity increases the risk of adverse pregnancy outcomes, including preterm birth and low birth weight. All medication decisions must be made in close consultation with both a rheumatologist and an obstetrician.
Non-Biologic Medications Generally Considered Low Risk
Several conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) possess well-established safety profiles and are often continued during pregnancy. Hydroxychloroquine is widely recommended for continuation throughout gestation to reduce the risk of maternal flares. Extensive data indicate this medication does not increase the risk of major congenital malformations. Similarly, Sulfasalazine is considered compatible with pregnancy and is frequently maintained as a first-line treatment.
When using Sulfasalazine, patients must take a high-dose folic acid supplement, as the drug can interfere with folate absorption. For acute flares, low-dose corticosteroids, such as prednisone or prednisolone, can be used temporarily. These corticosteroids do not cross the placenta in significant amounts at low doses, but higher doses should be tapered to minimize maternal risks like gestational diabetes and high blood pressure.
Acetaminophen is the preferred option and safest analgesic for managing pain throughout pregnancy. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used cautiously during the first and early second trimesters, but must be stopped by 20 weeks of gestation. Continued use of NSAIDs after this point poses a risk of fetal renal dysfunction, which can lead to low amniotic fluid levels. NSAIDs are strictly avoided in the third trimester due to the risk of premature closure of the fetal ductus arteriosus.
Medications Contraindicated During Pregnancy
Certain powerful disease-modifying therapies carry significant risks of birth defects and must be discontinued well before conception. Methotrexate is highly teratogenic and is also used medically to terminate ectopic pregnancies. This drug must be stopped for a minimum of three months before conception is planned, and women should continue taking folic acid during this washout period.
Leflunomide is another csDMARD strictly contraindicated due to its highly teratogenic properties. Its active metabolite has a prolonged half-life, potentially remaining in the body for up to two years. Simply stopping the drug is insufficient, requiring a mandatory accelerated elimination procedure using a medication like cholestyramine. This “washout” must be followed by a blood test to confirm undetectable metabolite levels before conception is attempted. Other immunosuppressive agents, such as cyclophosphamide, are also avoided throughout pregnancy.
Safety Profiles of Biologic and Targeted DMARDs
The safety data for biologic and targeted therapies are complex, as most are large antibody proteins that can cross the placental barrier. Tumor Necrosis Factor (TNF) inhibitors are generally considered safe for use through the first and second trimesters. Since they are immunoglobulin G (IgG) antibodies, their active transfer to the fetus increases exponentially starting around 28 weeks of gestation.
The common recommendation is to discontinue these TNF inhibitors by the beginning of the third trimester (20 to 24 weeks) to minimize the newborn’s exposure and theoretical risk of neonatal immunosuppression. A notable exception is Certolizumab pegol, which is structurally modified (pegylated) and lacks the Fc portion responsible for active placental transfer. Certolizumab pegol is often the preferred biologic and can be continued throughout the entire pregnancy if necessary to maintain disease control.
TNF inhibitors include:
- Adalimumab
- Etanercept
- Infliximab
- Golimumab
Other non-TNF biologics, such as the B-cell depleting agent Rituximab, are not recommended, particularly in the third trimester where they can suppress the neonatal B-cell count. Abatacept, a selective T-cell co-stimulation modulator, is generally discontinued before conception due to limited safety data. The newer class of small-molecule Targeted Synthetic DMARDs, known as Janus Kinase (JAK) inhibitors (Tofacitinib and Baricitinib), are also not recommended for use in pregnancy. These drugs should be stopped at least four weeks prior to attempting conception, as they cross the placenta easily and lack sufficient data to guarantee fetal safety.
Strategic Management of Rheumatoid Arthritis During Pregnancy
A coordinated strategy is necessary to ensure the best outcomes for both mother and baby, starting long before conception. Pre-conception counseling is the time to switch patients from contraindicated medications to pregnancy-compatible alternatives like Hydroxychloroquine or Sulfasalazine. Achieving low disease activity or remission for at least three to six months prior to conception is essential, as active disease is a significant risk factor for adverse pregnancy outcomes.
RA disease activity frequently improves in 40 to 70 percent of women during the second and third trimesters, often attributed to hormonal changes. However, up to 90 percent of women will experience a flare in the postpartum period, typically within the first few months after delivery. Managing a flare during pregnancy relies on the use of low-dose corticosteroids or non-biologic DMARDs that have been deemed safe.
Postpartum management is important due to the high risk of disease flare, which can severely impact a new mother’s ability to care for her infant. Many anti-rheumatic medications, including Hydroxychloroquine, Prednisone, and Sulfasalazine, are considered compatible with breastfeeding. If pain relief is needed, ibuprofen is the preferred NSAID for breastfeeding mothers. Maintaining continuous disease control requires coordinating care among a specialized team of providers.