What is the recommended treatment for rheumatoid arthritis (RA) in pregnancy?

Treatment for Rheumatoid Arthritis in Pregnancy

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 and Optimization

Switch from teratogenic medications at least 3 months before conception to allow adequate time for disease stabilization on pregnancy-compatible alternatives. 2

Medications That Must Be Discontinued:

• Methotrexate: Stop 1-3 months before conception due to teratogenicity 2, 3
• Leflunomide: Discontinue and perform cholestyramine washout if detectable serum metabolite levels exist 2, 3
• Mycophenolate and cyclophosphamide: Discontinue at least 3-12 weeks prior to conception 3

Critical Pre-Pregnancy Steps:

• Observe disease stability for several months on pregnancy-compatible medications before attempting conception 2
• Optimize disease control before pregnancy as active RA increases risk of preterm delivery, low birth weight, and fetal loss 1
• Co-management with maternal-fetal medicine specialists is strongly preferred throughout the pregnancy journey 2

First-Line Pregnancy-Compatible Medications

Strongly Recommended Throughout Pregnancy:

Hydroxychloroquine is the cornerstone medication with excellent safety profile and potential maternal/fetal benefits. 2, 1, 3

Sulfasalazine is safe at doses up to 2 g/day throughout pregnancy, but requires daily folic acid supplementation due to inhibition of folate absorption. 2, 3, 4

Azathioprine/6-mercaptopurine can be used at doses up to 2 mg/kg daily in women with normal thiopurine metabolism. 2, 1, 3

Certolizumab is the preferred TNF inhibitor as it lacks an Fc chain and has minimal placental transfer, allowing continuation throughout all trimesters. 2, 1, 3

Conditionally Recommended:

Other TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) can be continued through the first and second trimesters when placental transfer is minimal. 2, 1

• Consider discontinuing in the third trimester if disease is well-controlled to avoid high neonatal drug levels 1

Calcineurin inhibitors (tacrolimus, cyclosporine) are compatible during pregnancy at the lowest effective dose. 2, 3

Glucocorticoid Management

Low-dose prednisone (≤10 mg daily) can be continued throughout pregnancy when clinically indicated. 2, 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. 2, 1

Use only non-fluorinated glucocorticoids (prednisone, prednisolone) as fluorinated forms (dexamethasone, betamethasone) cross the placenta extensively and should not be used for routine RA management. 1

NSAID Use: Trimester-Specific Approach

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

Discontinue before conception if subfertility is present, as NSAIDs may cause unruptured follicle syndrome. 2, 1

Third trimester: NSAIDs are absolutely contraindicated due to risk of premature ductus arteriosus closure. 2, 1

Managing Active Disease During Pregnancy

If RA flares during pregnancy, initiate or continue pregnancy-compatible steroid-sparing medications immediately, as both uncontrolled disease and prolonged high-dose steroids pose significant maternal and fetal risks. 2, 1

Treatment Algorithm for Active Disease:

1. Add or optimize hydroxychloroquine if not already at therapeutic dose 1
2. Consider sulfasalazine (with folic acid supplementation) 3
3. Add azathioprine if additional immunosuppression needed 1, 3
4. Continue or initiate certolizumab for severe disease 1
5. Use low-dose prednisone as bridge therapy while steroid-sparing agents take effect 1

Medications to Absolutely Avoid

Non-TNF biologics (abatacept, rituximab, tocilizumab) should be discontinued at the time of positive pregnancy test due to limited safety data. 1

JAK inhibitors (tofacitinib, baricitinib) have no safety data available and should be avoided entirely. 1

Monitoring and Follow-Up

Monitor disease activity at least once per trimester with laboratory assessments. 2

Maintain concurrent care with maternal-fetal medicine specialists throughout pregnancy for optimal outcomes. 2, 1

Critical Pitfalls to Avoid

Do not discontinue all medications assuming pregnancy will induce remission—approximately 40% of patients do not experience remission and require ongoing treatment. 1

Do not delay switching from teratogenic medications—allow several months to establish efficacy of pregnancy-compatible alternatives before conception. 2, 1

Do not continue NSAIDs into the third trimester, even if disease control is suboptimal; switch to other pregnancy-compatible options immediately. 2, 1

Do not forget folic acid supplementation when using sulfasalazine, as it inhibits folate absorption and may increase risk of neural tube defects. 3, 4

Do not use fluorinated corticosteroids for routine RA management during pregnancy. 1

Breastfeeding Compatibility

All first-line pregnancy-compatible medications are safe during breastfeeding: hydroxychloroquine, sulfasalazine, azathioprine, low-dose prednisone, and all TNF inhibitors. 3