How should ankylosing spondylitis be managed during pregnancy?

Management of Ankylosing Spondylitis During Pregnancy

Continue pregnancy-compatible medications throughout pregnancy to maintain disease control, as ankylosing spondylitis frequently flares during pregnancy and postpartum, and active disease poses greater risks than appropriately selected medications. 1, 2

Pre-Pregnancy Optimization

• Achieve disease quiescence before conception using pregnancy-compatible medications, allowing several months to confirm efficacy before attempting pregnancy 2
• Discontinue methotrexate and leflunomide at least 3 months before conception and transition to pregnancy-compatible alternatives 2
• Counsel patients that unlike rheumatoid arthritis (which often improves during pregnancy), ankylosing spondylitis typically shows unaltered or worsened symptoms, particularly back pain and functional impairment 3, 4

Disease Course During Pregnancy

• Disease flares occur in 25–80% of patients during pregnancy and 30–100% during the postpartum period, making continuous treatment essential 5
• Most patients experience higher disease activity scores during pregnancy, with frequent increases in the second trimester and some mitigation in the third trimester 4
• Pain scores remain continuously elevated throughout pregnancy in ankylosing spondylitis patients compared to rheumatoid arthritis patients 4
• Despite increased disease activity, pregnancy outcomes are generally favorable with no increased risk of pre-eclampsia, though there is an increased risk of prematurity (pooled OR 1.99) and small for gestational age (pooled OR 2.41) 6, 5

First-Line Pregnancy-Compatible Medications

TNF Inhibitors (Preferred Biologics)

• All TNF inhibitors (infliximab, adalimumab, golimumab, etanercept, certolizumab) can be used throughout pregnancy with no increased risk of congenital malformations, miscarriage, or adverse pregnancy outcomes 1
• Certolizumab is the preferred TNF inhibitor because it lacks an Fc chain, resulting in minimal to undetectable placental transfer and no need to alter infant vaccination schedules 1, 2
• For whole IgG1-based TNF inhibitors (infliximab, adalimumab, golimumab), consider stopping by gestational week 20 if disease is well-controlled to minimize neonatal drug levels and allow live vaccination at 6 months 1
• For Fc fusion proteins (etanercept), consider stopping by gestational week 30–32 if disease is well-controlled 1

Non-TNF Biologics

• Secukinumab (IL-17 inhibitor) may be used if needed to control maternal disease, with current evidence showing no increased adverse pregnancy outcomes compared to background population rates 1
• Ixekizumab (IL-17 inhibitor) may also be used if needed, though evidence is more limited than for secukinumab 1
• Other non-TNF biologics (abatacept, anakinra, tocilizumab, sarilumab) have weaker evidence but may be continued if necessary for disease control 1

NSAIDs

• NSAIDs are conditionally recommended in the first and second trimesters for symptom control, with nonselective NSAIDs preferred over COX-2 inhibitors 2
• Discontinue all NSAIDs before the third trimester due to risk of premature ductus arteriosus closure 2
• Avoid NSAIDs before conception if subfertility is present, as they may cause unruptured follicle syndrome 2

Glucocorticoids

• Low-dose prednisone (≤10 mg daily) is conditionally recommended throughout pregnancy when clinically indicated for disease control 2
• Prednisone/prednisolone are extensively metabolized by the placenta (≈90% inactivation), resulting in minimal fetal exposure 7, 8
• Higher doses must be tapered to <20 mg daily, adding pregnancy-compatible steroid-sparing agents (azathioprine, TNF inhibitors) as needed 2
• Never use fluorinated corticosteroids (dexamethasone, betamethasone) for maternal disease management, as these cross the placenta freely and can suppress the fetal hypothalamic-pituitary-adrenal axis 7, 8

Additional Pregnancy-Compatible Options

• Sulfasalazine is strongly recommended as safe throughout pregnancy for disease control 2
• Azathioprine is strongly recommended as a pregnancy-compatible immunosuppressant that can be added when disease control is insufficient 2, 7

Medications to Absolutely Avoid

• Methotrexate and leflunomide are absolutely contraindicated throughout pregnancy due to teratogenic effects 2
• JAK inhibitors (tofacitinib, baricitinib) have no safety data and should be avoided entirely 2
• Conventional synthetic DMARDs are discouraged for pure axial involvement 9

Management of Active Disease During Pregnancy

• If disease flares during pregnancy, initiate or continue pregnancy-compatible steroid-sparing medications (TNF inhibitors, IL-17 inhibitors, azathioprine), as both uncontrolled disease and prolonged high-dose steroids pose significant maternal and fetal risks 2
• Do not discontinue all medications assuming pregnancy will induce remission—this is a critical pitfall, as most ankylosing spondylitis patients experience worsening symptoms 3, 4
• Reassess diagnosis and consider comorbidities if treatment failure occurs 9

Disease Activity Monitoring

• Use the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for monitoring, as it correlates well with disease activity without interference from pregnancy-related symptoms 4, 10
• Monitor disease activity at least once per trimester with laboratory assessments 2, 7
• Functional indices may be confounded by physiological changes of late pregnancy and should be interpreted cautiously 4

Infant Vaccination Considerations

• Nonlive vaccines can be administered to all infants after exposure to any biologic during pregnancy according to the normal schedule 1
• Delay BCG vaccination for 6 months in infants exposed in utero to IgG1-based TNF inhibitors (infliximab, adalimumab, golimumab) after gestational week 20, or etanercept after week 32, due to rare cases of fatal disseminated BCG infection 1
• Certolizumab-exposed infants require no alteration to vaccination schedules, including live vaccines 1
• Rotavirus vaccination can proceed on schedule regardless of TNF inhibitor exposure 1

Multidisciplinary Care

• Maintain concurrent care with maternal-fetal medicine specialists throughout pregnancy for optimal outcomes 2
• Emphasize lifestyle interventions, particularly exercise programs tailored to pregnancy, smoking cessation, and psychosocial support 10

Common Pitfalls to Avoid

• Do not discontinue effective biologics at conception or early pregnancy based on unfounded safety concerns—the evidence strongly supports continuation when needed for disease control 1, 2
• Do not delay switching from teratogenic medications—allow several months before conception to establish efficacy of pregnancy-compatible alternatives 2
• Do not continue NSAIDs into the third trimester, even if disease control is suboptimal; switch to other pregnancy-compatible options 2
• Do not use fluorinated corticosteroids for routine disease management 7, 8
• Do not assume pregnancy will improve ankylosing spondylitis symptoms as it does in rheumatoid arthritis—most patients experience stable or worsened disease 3, 4