Are disease-modifying therapies (DMTs) like interferon beta (IFN-β) and glatiramer acetate safe for pregnant women with multiple sclerosis (MS)?

Safety of Disease-Modifying Therapies for Multiple Sclerosis During Pregnancy

Glatiramer acetate is considered safe for use during pregnancy in women with multiple sclerosis, while interferon beta may be used with caution, but other disease-modifying therapies should be avoided due to potential risks to the fetus.

Safety Profile of DMTs in Pregnancy

Injectable DMTs

• Glatiramer acetate:

  • FDA labeling indicates no evidence of adverse effects on embryo-fetal development in animal studies 1
  • Observational data support its safety during pregnancy 2, 3
  • Can be continued throughout pregnancy if needed for disease control
  • Low transfer into breast milk, making it compatible with breastfeeding 3

• Interferon beta (IFN-β):

  • Generally considered relatively safe but used with more caution than glatiramer acetate
  • May be associated with lower birth weight but not with increased risk of major malformations 2
  • Can be considered for use through pregnancy in women with active MS
  • Compatible with breastfeeding 3

Oral DMTs

• Fingolimod:

  • Contraindicated during pregnancy due to potential teratogenic effects 3
  • Requires discontinuation before conception with appropriate washout period
  • Associated with risk of severe rebound relapses during pregnancy if discontinued 3

• Teriflunomide:

  • Contraindicated during pregnancy due to known teratogenic potential 3, 4
  • Requires accelerated elimination procedure if pregnancy occurs during treatment 4

• Dimethyl fumarate:

  • Limited data on pregnancy outcomes
  • Generally recommended to discontinue before conception due to unclear risks 3

Monoclonal Antibodies

• Natalizumab:

  • May be continued through pregnancy in women with highly active MS 2, 3
  • Potential risk of hematological abnormalities in newborns if used in second trimester or later 4
  • Monitor fetus if continued during pregnancy

• Rituximab/Ocrelizumab:

  • Can be administered before conception with minimal fetal risk 2
  • Low transfer into breast milk 3
  • Consider timing of last dose before conception to minimize placental transfer

Management Algorithm for MS During Pregnancy

1. Pre-conception planning:

   • Optimize disease control before pregnancy
   • Switch from contraindicated medications to pregnancy-compatible options
   • For women with mild MS: Consider discontinuing all DMTs
   • For women with highly active MS: Consider cell-depleting therapies before conception or continuing natalizumab through pregnancy 2

2. During pregnancy:

   • Monitor disease activity with clinical assessments each trimester
   • Most women experience reduced relapse rates during pregnancy, especially in the third trimester 5
   • For active disease during pregnancy: Consider glatiramer acetate as first choice, interferon beta as second choice

3. Postpartum period:

   • Increased relapse risk in first 3 months postpartum 5
   • Resume DMT promptly in women with previously active disease
   • For women who wish to breastfeed: Consider glatiramer acetate, interferon beta, or monoclonal antibodies 3

Special Considerations

• Breastfeeding:

  • Associated with decreased risk of postpartum relapses 2
  • Should be encouraged when possible
  • Compatible with glatiramer acetate, interferon beta, natalizumab, and rituximab/ocrelizumab 3

• Assisted reproduction:

  • Unsuccessful procedures may increase relapse risk in the months following treatment 6
  • Consider continuing DMTs during fertility treatments if appropriate

• Pregnancy outcomes:

  • No increased risk for miscarriage or congenital malformations in women with MS 6
  • Slight tendency toward assisted delivery/cesarean section and reduced birth weights 6

Common Pitfalls to Avoid

1. Abrupt discontinuation of all DMTs: May lead to disease reactivation in women with previously active MS

2. Continuing contraindicated medications: Teriflunomide and fingolimod should be avoided due to known risks

3. Delaying treatment resumption postpartum: The first 3 months postpartum carry the highest relapse risk

4. Discouraging breastfeeding: Breastfeeding may be protective and is compatible with several DMTs

5. Inadequate monitoring: Regular assessment during pregnancy is essential, especially in women with previously active disease

By following these guidelines, clinicians can help women with MS navigate pregnancy safely while maintaining optimal disease control.