What are the guidelines for Disease Modifying Therapies (DMTs) in pregnancy for patients with Multiple Sclerosis (MS)?

Guidelines for Disease Modifying Therapies in Pregnancy for MS Patients

Disease Modifying Therapies (DMTs) for MS should be carefully managed before, during, and after pregnancy, with most DMTs discontinued before conception while some may be continued throughout pregnancy depending on disease activity and specific medication safety profiles.

Pre-Conception Planning

Disease Activity Assessment

• Pregnancy should be planned during periods of disease quiescence/low activity 1
• Laboratory assessment of disease activity should be performed at least once per trimester 2
• Women with highly active MS should achieve disease control before conception 1

DMT Management Before Pregnancy

1. First-line injectable therapies:

   • Glatiramer acetate: May be continued until conception and potentially throughout pregnancy 1, 3
   • Interferon-beta: May be continued until conception 1, 3

2. Oral DMTs:

   • Teriflunomide: CONTRAINDICATED

     • Must be discontinued due to known teratogenicity 4
     • Requires accelerated elimination procedure with cholestyramine or activated charcoal for 11 days before conception 4
     • Pregnancy must be excluded before initiating therapy 4

   • Fingolimod: CONTRAINDICATED

     • Associated with increased risk of fetal harm 1
     • Risk of severe rebound relapses upon discontinuation 1
     • Should be avoided in women planning pregnancy 1

   • Dimethyl fumarate:

     • Discontinue before conception due to unclear risks 1

3. Monoclonal antibodies:

   • Natalizumab:

     • May be used until conception 3
     • Risk of severe rebound relapses upon discontinuation 1
     • For highly active MS, may be considered for continuation throughout pregnancy with fetal monitoring 3

   • Rituximab/Ocrelizumab:

     • May be administered before conception 3
     • Long-lasting effects allow for treatment discontinuation during pregnancy 3

   • Alemtuzumab:

     • Avoid in women planning pregnancy due to unclear risks 1
     • Requires contraception for 4 months after administration

During Pregnancy

DMT Management During Pregnancy

• Most DMTs should be discontinued before conception
• Exceptions based on benefit-risk assessment:

1. May continue throughout pregnancy if benefits outweigh risks:

   • Glatiramer acetate: Observational data support safety 3
   • Interferon-beta: Observational data support safety 3
   • Natalizumab: Consider for women with highly active MS, with fetal monitoring 3

2. Absolutely contraindicated during pregnancy:

   • Teriflunomide: Known teratogenicity and embryolethality 4
   • Fingolimod: Risk of fetal harm 1

Managing Disease Activity During Pregnancy

• Many women experience reduced disease activity during pregnancy, particularly in the third trimester 5
• For women with active disease during pregnancy:
  • Strongly recommend initiating or continuing a pregnancy-compatible steroid-sparing medication 2
  • Consider corticosteroids for acute relapses (short courses preferred)

Special Considerations

• Women who discontinue fingolimod or natalizumab may experience severe rebound relapses during pregnancy 1
• For women with highly active MS, cell-depleting therapies before conception or continued natalizumab throughout pregnancy may be considered 3

Postpartum Management

Breastfeeding and DMTs

• Breastfeeding is associated with decreased risk of postpartum relapses 3
• DMTs compatible with breastfeeding:
  • Glatiramer acetate: Low transfer into breastmilk 1, 3
  • Interferon-beta: Low transfer into breastmilk 1, 3
  • Natalizumab: Likely low transfer into breastmilk 1
  • Rituximab/Ocrelizumab: Likely low transfer into breastmilk 1

Resuming DMT After Delivery

• For women with low disease activity: May not require immediate DMT resumption (>40% of women with mild MS) 1
• For women with moderate-high disease activity: Resume DMT immediately postpartum 1
• If treatment needs to be resumed during breastfeeding, opt for glatiramer acetate, interferon beta, natalizumab, or rituximab/ocrelizumab 1

Common Pitfalls and Caveats

1. Accidental exposure:

   • If pregnancy occurs while on contraindicated DMTs (teriflunomide, fingolimod), consult immediately for risk assessment and management
   • For teriflunomide, accelerated elimination procedure should be initiated 4

2. Rebound disease activity:

   • Discontinuation of fingolimod or natalizumab may lead to severe rebound relapses 1
   • Consider continuing natalizumab throughout pregnancy in women with highly active disease 3

3. Postpartum relapse risk:

   • Increased risk of relapses in the first 3-6 months postpartum
   • Early DMT resumption may be necessary for women with active disease

4. Monitoring requirements:

   • Regular clinical and MRI monitoring before conception
   • Clinical monitoring throughout pregnancy
   • Close follow-up in the postpartum period

By following these guidelines, clinicians can help women with MS navigate pregnancy safely while minimizing both disease activity and risks to the developing fetus.