What are the management guidelines and medications for Rheumatoid Arthritis (RA) in pregnancy, particularly with complications such as Interstitial Lung Disease (ILD), sepsis, and Acute Respiratory Distress Syndrome (ARDS), and how to manage associated hypokalemia?

Management of Rheumatoid Arthritis During Pregnancy

Hydroxychloroquine and sulfasalazine are the safest DMARDs to use during pregnancy for rheumatoid arthritis management, and should be continued throughout pregnancy if needed for disease control. 1, 2, 3

Safe Medications During Pregnancy

First-Line Options

• Hydroxychloroquine is strongly recommended as safe throughout pregnancy and should be continued for disease control 1, 2, 3
• Sulfasalazine is strongly recommended as safe throughout pregnancy at doses up to 2-3 g/day, but requires daily folic acid supplementation due to its inhibition of folate absorption 1, 3, 4
• Low-dose glucocorticoids (≤10 mg daily prednisone or equivalent) can be continued during pregnancy if clinically indicated 1
• For higher doses of glucocorticoids, tapering to <20 mg daily of prednisone is strongly recommended, adding a pregnancy-compatible steroid-sparing agent if necessary 1

Additional Safe Options

• Azathioprine/6-mercaptopurine is conditionally recommended as safe during pregnancy at doses up to 2 mg/kg/day 1, 3
• Calcineurin inhibitors (tacrolimus and cyclosporine) are conditionally recommended as compatible for use during pregnancy 1, 3
• Colchicine is strongly recommended as compatible with pregnancy at doses of 1-2 mg/day 1, 3

Biologic DMARDs

• Certolizumab is strongly recommended for continuation throughout pregnancy as it has minimal placental transfer due to lack of an Fc chain 1, 3
• Other TNF inhibitors (infliximab, etanercept, adalimumab, golimumab) are conditionally recommended for continuation during the first and second trimesters, but should be discontinued in the third trimester due to significant placental transfer 1, 3
• Non-TNF inhibitor biologics (anakinra, rituximab, belimumab, abatacept, tocilizumab, secukinumab, ustekinumab) should be discontinued during pregnancy but may be used in the periconception period 1, 3

Medications to Avoid During Pregnancy

• Methotrexate is teratogenic and must be discontinued 1-3 months before conception 3, 5, 6
• Leflunomide is teratogenic and must be discontinued before pregnancy 3, 5, 7
• Cyclophosphamide is teratogenic and should be discontinued at least 12 weeks prior to conception 3
• Mycophenolate mofetil is teratogenic and should be discontinued before pregnancy 3
• NSAIDs can be used in the first and second trimesters but are strongly recommended against in the third trimester due to risk of premature closure of the ductus arteriosus 1, 8
• If the patient is having difficulty conceiving, NSAIDs should be discontinued in the preconception period due to possible NSAID-induced unruptured follicle syndrome 1

Management Algorithm for RA During Pregnancy

1. Pre-conception planning:

   • Achieve optimal disease control before conception 2, 3
   • Discontinue teratogenic medications (methotrexate, leflunomide, cyclophosphamide, mycophenolate) 3, 5, 6
   • Transition to pregnancy-compatible medications (hydroxychloroquine, sulfasalazine) 1, 2, 3
   • Add folic acid supplementation (5 mg/day) with sulfasalazine use 3, 4

2. During pregnancy:

   • Continue hydroxychloroquine and sulfasalazine throughout pregnancy 1, 2, 3
   • Use low-dose glucocorticoids (≤10 mg daily prednisone) if needed for disease flares 1
   • For moderate-severe disease requiring biologics, certolizumab is preferred throughout pregnancy 1, 3
   • Other TNF inhibitors can be used in first and second trimesters but should be discontinued in third trimester 1, 3
   • NSAIDs can be used in first and second trimesters but must be discontinued in third trimester 1, 8

3. Monitoring during pregnancy:

   • Assess disease activity at least once per trimester 2
   • Monitor for medication side effects and adjust dosages as needed 2
   • Monitor for pregnancy complications such as preterm delivery and low birth weight 2

Breastfeeding Considerations

• Hydroxychloroquine, sulfasalazine, rituximab, and all TNF inhibitors are strongly recommended as compatible with breastfeeding 1, 2, 3
• Prednisone <20 mg daily (or equivalent) is compatible with breastfeeding 1
• With prednisone ≥20 mg daily, delay breastfeeding or discard breast milk accumulated in the 4 hours following glucocorticoid administration 1
• Azathioprine/6-mercaptopurine, calcineurin inhibitors, NSAIDs, and non-TNF inhibitor biologics are conditionally recommended as compatible with breastfeeding 1, 2
• Cyclophosphamide, leflunomide, mycophenolate mofetil, and thalidomide should not be used while breastfeeding 1
• Methotrexate is conditionally recommended against during breastfeeding despite minimal passage into breast milk 1

Common Pitfalls to Avoid

• Discontinuing effective medications unnecessarily during pregnancy planning can lead to disease flares 2, 3
• Failing to provide folic acid supplementation with sulfasalazine can lead to folate deficiency 3, 4
• Continuing NSAIDs into the third trimester can cause premature closure of the ductus arteriosus 1, 8
• Overlooking the need for disease control before conception increases risks of adverse pregnancy outcomes 2, 3
• Abrupt discontinuation of medications when pregnancy is diagnosed can harm both mother and fetus 3
• Ignoring breastfeeding benefits by discouraging women from breastfeeding while taking compatible medications 3