What are the recommendations for managing rheumatoid arthritis (RA) in pregnancy?

Management of Rheumatoid Arthritis in Pregnancy

Continue hydroxychloroquine, sulfasalazine, and azathioprine throughout pregnancy, discontinue methotrexate and leflunomide at least 1-3 months before conception, and maintain disease control with pregnancy-compatible medications to optimize both maternal and fetal outcomes. 1

Pre-Pregnancy Planning and Counseling

Achieve disease quiescence before conception to minimize adverse pregnancy outcomes including preterm delivery, low birth weight, and intrauterine growth restriction. 1, 2 Active RA during pregnancy increases maternal and fetal morbidity, making pre-pregnancy disease control essential. 3

Medication Adjustments Before Conception

Discontinue teratogenic medications well in advance:

• Methotrexate: Stop 1-3 months before conception 1, 3, 4
• Leflunomide: Discontinue 24 months prior OR check serum metabolite levels and perform cholestyramine washout 1
• Mycophenolate: Stop before conception 1, 3
• Cyclophosphamide: Discontinue at least 12 weeks prior to conception 1, 3

Transition to pregnancy-compatible alternatives and observe for several months to ensure efficacy and tolerability before attempting conception. 1 This observation period allows assessment of disease stability on the new regimen. 1

Medications Safe Throughout Pregnancy

Strongly Recommended (Continue Throughout)

Hydroxychloroquine is strongly recommended to continue during pregnancy and should be started if not already prescribed (unless contraindicated). 1, 5 It reduces lupus flares, decreases preterm birth rates, and reduces intrauterine growth retardation. 5

Sulfasalazine can be continued at doses up to 2 g/day, but requires daily folic acid supplementation (1 mg daily starting 3 months before conception) due to folate absorption inhibition. 1, 3, 6

Azathioprine is safe at doses up to 2 mg/kg daily in women with normal thiopurine metabolism. 1, 3

Certolizumab is strongly recommended for continuation throughout pregnancy due to minimal placental transfer (lacks Fc chain). 1

Conditionally Recommended

Calcineurin inhibitors (tacrolimus and cyclosporine) can be used at the lowest effective dose, monitored by trough levels. 1, 3

Colchicine is compatible at doses of 1-2 mg/day. 1, 3

Other TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) may be continued through the first and second trimesters. 1 If disease is well-controlled, consider discontinuing in the third trimester to minimize neonatal drug exposure; however, if disease remains active, continuing through delivery is acceptable despite significant placental transfer. 1

Corticosteroid Management

Low-dose prednisone (≤10 mg daily or nonfluorinated equivalent) can be continued throughout pregnancy. 1

Higher doses should be tapered to <20 mg daily, adding a pregnancy-compatible steroid-sparing agent if necessary to maintain disease control. 1 Prolonged high-dose glucocorticoid use carries maternal and fetal risks. 1

Stress-dose steroids at delivery:

• Do NOT give for vaginal delivery 1
• DO give for cesarean delivery 1

NSAIDs: Timing-Specific Restrictions

Avoid NSAIDs in the third trimester due to risk of premature ductus arteriosus closure. 1 This is a strong recommendation. 1

Use nonselective NSAIDs over COX-2 inhibitors in the first two trimesters due to lack of data on COX-2-specific agents. 1

Consider discontinuing NSAIDs pre-conception if difficulty conceiving, as they may cause unruptured follicle syndrome leading to subfertility. 1

Biologics: Limited Data Agents

Non-TNF biologics (rituximab, belimumab, anakinra, abatacept, tocilizumab, secukinumab, ustekinumab) should be stopped when pregnancy is confirmed, as they likely cross the placenta significantly after the second trimester. 1

Exception: Rituximab may be used for organ- or life-threatening disease during pregnancy despite general recommendation to discontinue. 1

No recommendations exist for JAK inhibitors (tofacitinib, baricitinib) or apremilast due to insufficient data. 1 These should be avoided.

Breastfeeding-Compatible Medications

Strongly compatible with breastfeeding:

• Hydroxychloroquine, sulfasalazine, colchicine, rituximab, all TNF inhibitors 1, 3
• Prednisone <20 mg daily (or nonfluorinated equivalent) 1

For prednisone ≥20 mg daily: Delay breastfeeding or discard breast milk for 4 hours after administration 1

Conditionally compatible:

• Azathioprine, cyclosporine, tacrolimus, NSAIDs, anakinra, belimumab, abatacept, tocilizumab, secukinumab, ustekinumab 1

Contraindicated during breastfeeding:

• Methotrexate (conditionally), leflunomide, mycophenolate, cyclophosphamide, thalidomide (all strongly) 1

Monitoring During Pregnancy

Assess disease activity at least once per trimester with laboratory testing as clinically indicated. 1 Active disease requires initiation or continuation of pregnancy-compatible steroid-sparing medications. 1

Co-management with rheumatology and maternal-fetal medicine specialists is preferred for optimal outcomes. 1

Critical Pitfalls to Avoid

Never abruptly discontinue all medications when pregnancy is diagnosed. This precipitates disease flares that harm both mother and fetus. 3 Continue pregnancy-compatible medications to maintain disease control. 1, 3

Do not overlook folic acid supplementation with sulfasalazine, as folate deficiency can occur. 3, 6

Do not delay preconception planning. Uncontrolled disease at conception significantly increases adverse pregnancy outcomes. 3, 2

Do not discourage breastfeeding in women taking compatible medications. The benefits of breastfeeding are substantial, and many RA medications are safe during lactation. 1, 3