2024 EULAR Recommendations for the Use of Antirheumatic Drugs in Reproduction, Pregnancy and Lactation ‑ Update

Annals of the Rheumatic Diseases, 2024 Task‑force output: 5 overarching principles + 12 formal‑consensus‑points‑to‑consider；systematic‑literature‑review covering 2000‑2023, Delphi expert‑voting processAnnals of ...

Abstract

Objective To deliver updated‑consensus‑based clinical guidance for antirheumatic‑drug prescribing for persons with inflammatory rheumatic‑disease across preconception, pregnancy, lactation, and for male patients. The core paradigm: controlling maternal disease activity outweighs theoretical drug‑related risks; uncontrolled‑disease itself carries major obstetric‑and‑foetal‑hazardscuris.ku.d....

Methods Systematic‑literature‑review; multi‑disciplinary task‑force (rheumatologists, obstetricians, pharmacologists, patient‑representatives); modified‑Delphi‑voting for each principle‑and‑recommendation‑statementAnnals of ....

Conclusion Pre‑conception counselling and optimisation of disease‑activity are mandatory. Several conventional synthetic DMARDs, selected calcineurin‑inhibitors and biologics are compatible with pregnancy‑and‑lactation. Teratogenic agents must be discontinued well‑before‑conception. Biologic‑DMARDs including all TNF‑inhibitors may be continued throughout‑pregnancy under individualised risk‑benefit‑judgement. Most bDMARDs are compatible with breastfeeding. Prescribing‑advice is also provided for male partners wishing‑to‑conceiveAnnals of ....

Keywords: rheumatic‑disease; antirheumatic‑drugs; preconception; pregnancy; lactation; reproduction; EULAR‑recommendation

Overarching Principles (5 core‑principles)

1. Pre‑conception counselling is standard‑of‑care for all women/people of‑child‑bearing‑potential with inflammatory rheumatic‑disease. Optimise disease‑control prior‑to‑conception.
2. Treatment‑decisions balance foetal‑infant‑safety against maternal‑flare‑risk. Untreated‑active‑disease increases adverse‑pregnancy‑outcomes.
3. Medication‑selection uses best‑available‑real‑world‑human‑data; animal‑only‑toxicology‑data are not the primary‑decision‑driver.
4. Shared‑decision‑making between clinician‑and‑patient for every drug‑choice.
5. Multidisciplinary collaboration: rheumatology, obstetrics‑maternal‑foetal‑medicine, clinical‑pharmacology, genetic‑counselling as‑requiredcuris.ku.d....

1. Pre‑conception & pregnancy‑period recommendations

1.1 Conventional‑synthetic DMARDs (csDMARDs) — compatible during pregnancy

• Hydroxychloroquine / chloroquine: continue throughout preconception‑pregnancy‑lactation; do‑not‑discontinue at conception (strong‑support).
• Sulfasalazine: safe; supplement folate.
• Azathioprine / 6‑mercaptopurine: permissible at standard‑therapeutic‑doses.
• Colchicine: compatible for continuation in pregnancy.
• Ciclosporin, tacrolimus (CNI): acceptable for disease‑control‑during‑pregnancyAnnals of ....

1.2 Agents to STOP BEFORE conception (contra‑indicated in pregnancy)

• Methotrexate; mycophenolate‑mofetil / mycophenolic‑acid; cyclophosphamide.
• Leflunomide: stop pre‑conception; consider cholestyramine wash‑out‑protocol prior‑to‑attempting‑pregnancy.
• JAK‑inhibitors (tofacitinib, baricitinib, filgotinib, upadacitinib etc.): discontinue before conception; human‑pregnancy‑data remain insufficient for routine‑use‑in‑pregnancyMedscape.

1.3 NSAIDs & glucocorticoids

• NSAIDs: restrict‑use in pregnancy. Avoid‑after‑20 weeks of gestation; short‑course low‑dose may‑be‑considered early‑gestation if no‑alternatives.
• Glucocorticoids: keep dose‑as‑low‑as‑possible; minimise long‑term high‑dose prednisone/prednisolone; higher‑steroid‑exposure associates with prematurity, gestational‑diabetes, foetal‑growth‑restriction riskcuris.ku.d....

1.4 Biologic DMARDs (bDMARDs)

1. All TNF‑α‑inhibitors (certolizumab‑pegol, adalimumab, etanercept, infliximab, golimumab): may‑be‑continued through‑entire‑pregnancy after risk‑benefit‑assessment.
   • Certolizumab‑pegol: minimal‑placental‑transfer, preferred‑if‑continuous‑full‑trimester‑biologic‑exposure‑is‑required.
   • Other‑TNFi cross‑placenta increasingly in late‑pregnancy; decision‑to‑taper/hold in third‑trimester depends‑on‑disease‑stability, not absolute‑mandatory‑stop rule.
2. Non‑TNF‑biologics (abatacept, rituximab, belimumab, anakinra, tocilizumab, IL‑17/‑23‑inhibitors): limited‑human‑gestation‑data; only‑use‑during‑pregnancy if no‑other‑effective‑option exists for‑severe‑refractory‑diseasePMC.

Infant‑vaccination‑note: live‑vaccines (e.g. BCG) should‑be‑delayed in infants with documented in‑utero‑biologic‑exposure; follow‑local‑immunisation‑protocols. Inactivated‑vaccines can‑be‑administered normallyMedscape.

2. Lactation / breastfeeding recommendations

Drugs considered compatible with breastfeeding:

• Antimalarials (HCQ / chloroquine), colchicine, sulfasalazine, azathioprine‑6‑MP, ciclosporin, tacrolimus, low‑dose‑prednisone / prednisolone, IVIG, short‑course‑NSAIDs (ibuprofen‑preferred).
• All‑bDMARDs (including‑TNFi and‑most‑non‑TNF‑biologics): compatible‑with‑breastfeeding; very‑low‑milk‑transfer; protein‑biologics are largely degraded within‑infant‑gastro‑intestinal‑tract.

JAK‑inhibitors: insufficient‑data; avoid‑during‑lactation. Methotrexate, mycophenolate, cyclophosphamide, leflunomide: contra‑indicated‑while‑breast‑feeding.

3. Drug‑use in male patients planning conception

• Most antirheumatic‑agents including: hydroxychloroquine, sulfasalazine, azathioprine, colchicine, ciclosporin, tacrolimus, NSAIDs, glucocorticoids, methotrexate (≤25 mg/week), mycophenolate, leflunomide, and all‑bDMARDs have no‑mandatory‑pre‑conception‑drug‑holiday for males.
• No requirement for men to stop these agents prior‑to‑partner‑conception. There‑is‑no‑evidence‑of‑increased‑teratogenic‑risk via paternal‑drug‑exposurecuris.ku.d....

4. Major updates compared with prior EULAR (2016) version

1. More permissive‑position for full‑trimester‑TNFi‑continuation, abolishing rigid universal‑third‑trimester‑stopping‑rule.
2. Formal‑statement that nearly‑all‑bDMARDs are compatible‑for‑breastfeeding.
3. Clear‑summary‑for‑male‑partner‑medication‑safety: most‑rheumatic‑drugs do‑not‑require‑stopping‑before‑conception.
4. Stronger‑warning‑for‑restricted‑NSAID‑use after 20 weeks’ gestation.
5. Explicit‑warning against JAK‑inhibitor‑exposure in pregnancy due‑to‑limited‑human‑data.
6. Standardised‑advice‑on‑live‑vaccine‑delay for infants exposed‑in‑utero‑to‑biologicsMedscape.