Results from a study evaluating pregnant patients with active multiple sclerosis (MS) suggest that maintaining natalizumab treatment during the first trimester may reduce the risk of disease reactivation during pregnancy compared to withdrawal of treatment at conception.
Researchers reported that the proportion of patients with relapse and disability progression during pregnancy were lower in the group who maintained natalizumab treatment through the first trimester (secured first trimester [SFT]) than in those who stopped treatment after conception (secured conception [SC]) (3.6% vs 38.5%, P <.005 and 3.6% vs 30.8%, P <.05, respectively).
“The present prospective observational study suggests that in patients with highly active RRMS, continuing natalizumab until the end of the first trimester of pregnancy may reduce the risk of relapse and disability progression during pregnancy as compared with stopping the treatment right after conception,” the study authors wrote.
The University Hospital of Marseille, France, initiated a standardized therapeutic in 2014 for patients with relapsing-remitting MS (RRMS) who were planning pregnancy. It included recommending natalizumab along with an anti-JC virus antibody index <1.5 throughout the first trimester of pregnancy.
Patients who refused to maintain natalizumab until the end of the first trimester were recommended to continue treatment until conception. In total, 46 pregnancies were prospectively followed (30 with SFT and 16 with SC).
Each natalizumab infusion was performed every 4 weeks, at 6 months of pregnancy, at 1 month after delivery, and at 3 months after delivery. Neurologists at the MS center evaluated patients within 1 month of conception and at 3 months after delivery on the Expanded Disability Status Scale (EDSS) score.
There were 2 spontaneous abortions among the 30 pregnancies in the SFT group and 3 spontaneous abortions in the SC group, resulting in 28 and 13 live births in both groups, respectively. Patients in the SC group had a higher disease duration at conception and a higher annualized relapse rate in the year before natalizumab compared with those in the SFT group (7.7 vs 6.8; P = .43 and 2.0 vs 1.8; P = .65, respectively). Additionally, mean EDSS score (range) at conception was 1.5 (1-2) in the SC group and 2 (1-3) in the SFT group (P = .72).
As the previously mentioned relapse rates showed a lower rate in the SFT group, researchers also noted that the probability of relapse during pregnancy was associated with the time when natalizumab was stopped (end of first trimester vs conception; odds ratio [OR], .02; 95% CI: 0.0002—0.42, P = .007) as well as the number of relapses in the year before natalizumab treatment (OR, 2.98; 95% CI: 1.004—12.96, P = .04;model intercept: P = .02).
The proportion of patients with relapse during the 1-year postpartum period did not differ between the 2 groups (7/13 (54%) in the SC group vs 13/28 (46%) in the SFT group; P = 0.74). At 12 months postpartum, the SC group had 2 complications (1 hemorrhage and 1 infection) and the SFT group had 4 (2 hemorrhages, 1 pre-eclampsia, and 1 hemolysis, elevated liver enzymes, low platelet count;P = .96).
“The present study suggests that continuing natalizumab until the end of first trimester may reduce the risk of disease reactivation during pregnancy in patients with active RRMS. Future studies in larger samples are mandatory to confirm these preliminary findings. These studies would also consider extended natalizumab dosing to reduce the number of infusions during pregnancy,” the study authors concluded.
Demortiere S, Rico A, Maarouf A, Boutiere C, Pelletier J, Audoin B. Maintenance of natalizumab during the first trimester of pregnancy in active multiple sclerosis. Mult Scler. Published online March 23, 2020. doi: 10.1177/1352458520912637