Therapeutic Management During Pregnancy and Relapse Risk in Women With Multiple Sclerosis

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Multiple sclerosis (MS) management in pregnant women requires careful consideration of disease-modifying therapies (DMTs) due to potential impacts on relapse risk.
• Understanding the effect of different DMT management strategies during pregnancy is crucial for optimizing patient outcomes.

Purpose of the Study:

• To evaluate the impact of disease-modifying therapy (DMT) management during pregnancy on the relapse rate in women with multiple sclerosis (MS).
• To compare the effectiveness of various therapeutic strategies, including DMT interruption, switching, or maintenance, in mitigating relapse risk during pregnancy.

Main Methods:

• A multicenter retrospective cohort study analyzed data from the French MS registry (1990-2023).
• Included were 6341 pregnancies in 4998 women with relapsing-onset MS, monitored for at least 18 months pre-delivery and 9 months post-delivery.
• Mediation analysis and longitudinal g-computation with random forest and mixed-effects Poisson models were used to estimate treatment effects on annualized relapse rate (ARR).

Main Results:

• DMT management during pregnancy significantly increased ARR during gestation (cRR, 1.13) and postpartum (cRR, 1.08).
• Prolonged interruption of natalizumab or use of fingolimod before pregnancy led to a substantial increase in ARR (cRR, 2.18 and 2.15, respectively).
• Compared to DMT interruption, the anti-CD20 strategy was most effective (cRR, 0.38), followed by natalizumab with short interruption (cRR, 0.80). Interferon β and glatiramer acetate showed less effectiveness.

Conclusions:

• Disease-modifying therapy management during pregnancy significantly elevates MS relapse risk, particularly with prolonged natalizumab interruption or fingolimod use.
• The most effective strategy to mitigate relapse risk involved using anti-CD20 therapies prior to pregnancy.
• These findings underscore the importance of personalized DMT management strategies for women with MS planning pregnancy.