What are the safest treatment options for managing rheumatoid arthritis (RA) during pregnancy?

Managing Rheumatoid Arthritis During Pregnancy

The safest and most effective approach is to achieve disease quiescence before conception using pregnancy-compatible medications, then maintain control throughout pregnancy with hydroxychloroquine, sulfasalazine, azathioprine, low-dose prednisone (≤10 mg daily), and certolizumab as first-line options. 1

Pre-Pregnancy Planning

Optimize disease control before conception to minimize maternal and fetal risks, as active RA increases the risk of preterm delivery, low birth weight, and fetal loss. 1, 2

Medication Transitions Before Pregnancy

• Discontinue teratogenic medications at least 3 months before conception, specifically methotrexate and leflunomide, and switch to pregnancy-compatible alternatives with several months of observation to ensure disease stability. 1, 3

• Test for anti-Ro/SSA and anti-La/SSB antibodies once before or early in pregnancy, as these guide fetal monitoring; do not repeat during pregnancy. 1

Pregnancy-Compatible Medications Throughout All Trimesters

Strongly Recommended (Safe Throughout Pregnancy)

• Hydroxychloroquine: Strongly recommended throughout pregnancy with excellent safety profile and potential maternal/fetal benefits. 1

• Sulfasalazine: Strongly recommended as safe throughout pregnancy for disease control. 1

• Azathioprine/6-mercaptopurine: Strongly recommended as pregnancy-compatible immunosuppressants. 1

• Certolizumab: Strongly recommended throughout pregnancy as it lacks an Fc chain and has minimal placental transfer, making it the preferred TNF inhibitor. 1

Conditionally Recommended

• Other TNF inhibitors (infliximab, etanercept, adalimumab, golimumab): Conditionally recommended during pregnancy, particularly in the first and second trimesters when placental transfer is minimal. 1, 4

  • If disease is well-controlled, consider discontinuing in the third trimester to avoid high neonatal drug levels. 1
  • If disease remains active, continuing through delivery is acceptable with informed consent about neonatal drug exposure. 1

• Calcineurin inhibitors (tacrolimus, cyclosporine): Conditionally recommended as compatible during pregnancy. 1

Glucocorticoid Management

• Low-dose prednisone (≤10 mg daily): Conditionally recommended throughout pregnancy when clinically indicated. 1

• Higher doses must be tapered to <20 mg daily, adding pregnancy-compatible steroid-sparing agents as needed to avoid maternal and fetal complications from prolonged high-dose exposure. 1

• Use nonfluorinated glucocorticoids only (prednisone, prednisolone, methylprednisolone), as fluorinated forms cross the placenta more readily. 1

NSAID Use: Trimester-Specific Approach

• First and second trimesters: Conditionally recommended, with nonselective NSAIDs preferred over COX-2 inhibitors due to limited data on the latter. 1

• Discontinue before conception if subfertility is present, as NSAIDs may cause unruptured follicle syndrome. 1

• Strongly contraindicated in the third trimester due to risk of premature ductus arteriosus closure. 1

Medications to Avoid

Absolutely contraindicated throughout pregnancy:

• Methotrexate and leflunomide: Teratogenic; must be discontinued 3 months before conception. 1, 3, 5

• Non-TNF biologics (abatacept, rituximab, tocilizumab): Should be discontinued at the time of positive pregnancy test due to limited safety data, though rituximab may be continued only for severe life-threatening disease. 1

• JAK inhibitors (tofacitinib, baricitinib): No safety data available; avoid entirely. 1

Active Disease Management During Pregnancy

If RA flares during pregnancy, strongly recommend initiating or continuing pregnancy-compatible steroid-sparing medications, as both uncontrolled disease and prolonged high-dose steroids pose significant maternal and fetal risks. 1

Treatment Algorithm for Active Disease:

1. Optimize hydroxychloroquine, sulfasalazine, or azathioprine as steroid-sparing agents. 1
2. Add or continue certolizumab if conventional DMARDs are insufficient. 1
3. Use low-dose prednisone (≤10 mg daily) for symptom control while steroid-sparing agents take effect. 1
4. Consider other TNF inhibitors if certolizumab is unavailable or ineffective, particularly in first/second trimesters. 1, 4

Critical Monitoring and Co-Management

• Maintain concurrent care with maternal-fetal medicine specialists throughout pregnancy for optimal outcomes. 1

• Monitor disease activity at least once per trimester with laboratory assessments. 1

• The FDA notes that cord blood etanercept levels varied from undetectable to 32% of maternal levels, emphasizing the importance of timing decisions about third-trimester continuation. 2

Common Pitfalls to Avoid

• Do not discontinue all medications assuming pregnancy will induce remission—approximately 40-60% of patients experience persistent or worsening disease activity. 6, 3

• Do not use fluorinated corticosteroids (dexamethasone, betamethasone) for routine RA management, as these cross the placenta extensively. 1

• Do not delay switching from teratogenic medications—allow several months to establish efficacy of pregnancy-compatible alternatives before conception. 1

• Do not continue NSAIDs into the third trimester, even if disease control is suboptimal; switch to other pregnancy-compatible options. 1