How to manage rheumatoid arthritis (RA) in a pregnant patient?

Managing Rheumatoid Arthritis During Pregnancy

The optimal approach to managing RA in pregnancy 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, as both active disease and uncontrolled inflammation pose greater risks to maternal and fetal outcomes than these medications. 1, 2

Pre-Pregnancy Planning and Counseling

Counsel all women with RA early and periodically about family planning, emphasizing that entering pregnancy with quiescent or low disease activity dramatically improves maternal and fetal outcomes. 1

Critical Pre-Conception Steps:

• Switch from teratogenic medications (methotrexate, leflunomide) to pregnancy-compatible alternatives at least 3 months before attempting conception, allowing several months to establish efficacy and tolerability of the new regimen 1, 2
• Methotrexate and leflunomide are absolutely contraindicated throughout pregnancy due to proven teratogenicity and must be discontinued well before conception 2, 3, 4, 5
• Test for anti-Ro/SSA and anti-La/SSB antibodies once before or early in pregnancy, as RA patients can carry these antibodies 1
• Establish multidisciplinary care with maternal-fetal medicine specialists before conception 1

Contraindications to Pregnancy:

Pregnancy may be contraindicated and should be discussed with the patient if severe organ damage exists, including pulmonary arterial hypertension (up to 20% maternal mortality), severe renal insufficiency, cardiomyopathy, or valvular dysfunction 1

Pregnancy-Compatible Medications: First-Line Options

Hydroxychloroquine (HCQ):

• Strongly recommend continuing HCQ if already prescribed, or starting if not on it and no contraindication exists 1, 2
• Excellent safety profile with potential maternal and fetal benefits throughout pregnancy 2, 4, 5

Sulfasalazine:

• Strongly recommended as safe throughout pregnancy for disease control 2, 4, 5

Azathioprine:

• Strongly recommended as a pregnancy-compatible immunosuppressant 2, 4, 5
• However, azathioprine should NOT be used for treating RA specifically in pregnant women according to FDA labeling, though it is used for other rheumatic conditions 6
• This creates a nuanced situation where guidelines support its use but the FDA label specifically contraindicates it for RA in pregnancy 6

Certolizumab (TNF Inhibitor):

• Strongly recommended throughout pregnancy as the preferred TNF inhibitor due to lack of Fc chain and minimal placental transfer 2

Other TNF Inhibitors:

• Conditionally recommend infliximab, etanercept, adalimumab, and golimumab during pregnancy, particularly in first and second trimesters when placental transfer is minimal 2, 4, 5
• Consider discontinuing TNF inhibitors in the third trimester if disease is well-controlled to avoid high neonatal drug levels 2

Glucocorticoid Management

• Low-dose prednisone or methylprednisolone (≤10 mg daily) is conditionally recommended throughout pregnancy when clinically indicated 2, 7
• Both prednisone and methylprednisolone are equally safe, as they undergo placental metabolism limiting fetal exposure to approximately 10% of maternal dose 7
• If doses exceed 20 mg daily, taper and add pregnancy-compatible steroid-sparing agents to avoid maternal complications (gestational diabetes, osteoporosis, infections) and fetal risks (preterm birth) 2, 7
• Never use fluorinated corticosteroids (dexamethasone, betamethasone) for routine RA management, as these cross the placenta extensively and are reserved only for fetal lung maturation 2, 7

NSAID Use: Timing is Critical

• Conditionally recommend NSAIDs only in the first and second trimesters, with nonselective NSAIDs preferred over COX-2 inhibitors 2, 8
• Discontinue NSAIDs before conception if subfertility is present, as they may cause unruptured follicle syndrome 2
• NSAIDs are absolutely contraindicated in the third trimester due to risk of premature ductus arteriosus closure 2, 8

Managing Active Disease During Pregnancy

If RA flares during pregnancy, strongly recommend initiating or continuing pregnancy-compatible steroid-sparing medications rather than relying solely on high-dose glucocorticoids. 1, 2

The rationale: Both uncontrolled active disease and prolonged high-dose steroids pose significant maternal and fetal risks, including preterm delivery, low birth weight, and fetal loss 2, 9, 10

Treatment Algorithm for Active Disease:

1. Optimize hydroxychloroquine and sulfasalazine dosing 2, 4
2. Add or continue certolizumab if needed 2
3. Use low-dose prednisone (≤10 mg daily) as bridge therapy, not maintenance 2, 7
4. Consider other TNF inhibitors in first/second trimester if inadequate response 2

Medications to Avoid Entirely

• Methotrexate and leflunomide: Absolutely contraindicated due to teratogenicity 2, 3, 4, 5
• Non-TNF biologics (abatacept, rituximab, tocilizumab): Discontinue at positive pregnancy test due to limited safety data 2
• JAK inhibitors (tofacitinib, baricitinib): No safety data available, avoid entirely 2

Monitoring and Co-Management

• Monitor disease activity with laboratory assessments at least once per trimester 1
• Maintain concurrent care with maternal-fetal medicine specialists throughout pregnancy 1, 2
• Distinguish normal pregnancy symptoms (malar erythema, anemia, elevated ESR, arthralgias) from true RA flares 1
• Differentiate preeclampsia from RA-related complications, requiring rheumatology and obstetric expertise working together 1

Common Pitfalls to Avoid

• Do not discontinue all medications assuming pregnancy will induce remission—only 75% of patients improve, and 25% continue with active disease requiring treatment 11, 10
• Do not delay switching from teratogenic medications—unplanned pregnancies in RA patients carry greater risk than planned pregnancies on compatible medications 1
• Do not continue NSAIDs into the third trimester even if disease control is suboptimal; switch to other pregnancy-compatible options 2, 8
• Do not use high-dose glucocorticoids as monotherapy—add steroid-sparing agents to minimize maternal and fetal complications 2, 7
• Do not ignore the paradigm shift: Modern evidence supports continuing pregnancy-compatible DMARDs and biologics rather than the outdated approach of discontinuing all medications except prednisone 1, 2

Expected Outcomes with Modern Management

Recent data demonstrate that with a treat-to-target approach using pregnancy-compatible medications, 90.4% of pregnant RA patients can achieve low disease activity or remission by the third trimester, compared to only 47.3% with older treatment paradigms 10