“MML” — the three drugs to washout, not just stop
- M — Methotrexate (3-month washout)
- M — Mycophenolate mofetil (6 weeks–3 months washout)
- L — Leflunomide (active cholestyramine washout, level-confirmed)
Rheumatology in Pregnancy
DMARDs, biologics, and autoimmune disease control across conception, pregnancy, and lactation.
Key takeaways
- 1
Active maternal disease at conception is a bigger risk to the pregnancy than most compatible medications — don't stop everything reflexively.
- 2
Three drugs are known human teratogens needing pre-conception washout: methotrexate, leflunomide, mycophenolate mofetil.
- 3
Hydroxychloroquine should be continued (or started) in SLE pregnancy — stopping it risks flare and worse outcomes.
- 4
Certolizumab is the anti-TNF of choice if therapy must continue into the third trimester (minimal placental transfer).
- 5
Colchicine must be continued in FMF — stopping risks flare/amyloidosis, not the baby.
- 6
aPL and anti-SSA/SSB antibodies should be checked in all SLE patients pre-conception or in early pregnancy.
Mnemonics
PROMISSE study — 5 predictors of poor SLE pregnancy outcome
- Lupus anticoagulant positive
- Antihypertensive medication use
- Physician global assessment >1 (active disease)
- Non-Caucasian ethnicity
- Thrombocytopenia (per 50K decrease)
Drugs in this chapter
Methotrexate
First-lineSingle-dose IM for stable ectopic pregnancy.
Hydroxychloroquine
First-lineSafe in pregnancy SLE/APS — continue throughout.
Azathioprine
First-lineIBD / SLE / transplant — compatible in pregnancy.
Prednisolone
First-lineMaternal disease control — minimal placental transfer.
Leflunomide
CautionContraindicated in pregnancy — needs an active washout, not just stopping.
Sulfasalazine
First-lineCompatible in pregnancy — give with folic acid.
Mycophenolate mofetil
CautionContraindicated — first-trimester loss and a recognisable malformation pattern.
Cyclophosphamide
CautionContraindicated — reserved for organ- or life-threatening flare only.
Ciclosporin / Tacrolimus
AlternativeCompatible — useful steroid-sparing option; monitor BP and renal function.
TNF-α inhibitors (Infliximab, Adalimumab, Certolizumab)
AlternativeCompatible — certolizumab preferred through third trimester (minimal placental transfer).
Rituximab
CautionCan be used for severe disease; expect transient neonatal B-cell depletion if given after ~20 weeks.
Colchicine
First-lineSafe and essential to continue in FMF — stopping risks amyloidosis, not the baby.
JAK inhibitors (Tofacitinib, Baricitinib, Upadacitinib)
CautionAvoid in pregnancy — small molecules cross the placenta freely; insufficient safety data.