Rituximab Suspension Preconception Tied to Reduced MS Reactivity in Women

Among women with highly progressive multiple sclerosis (MS) who plan to conceive, the suspension of rituximab/ocrelizumab prior to conception yields a lower likelihood of disease reactivity, compared to the suspension of natalizumab amid pregnancy, according to study findings published in Neurology.

With the advancement in disease-modifying therapies (DMTs), such as natalizumab and the anti-CD20 therapy, rituximab, women with increasingly active MS have the capability of conceiving with less repercussions. In previous studies, natalizumab was administered during the initial trimester and halted at the third trimester of pregnancy to deter MS relapse without negatively affecting the newborn; although, disease reactivity was observed post-delivery despite restarting natalizumab.

In comparison, rituximab was found in 2016 to be another form of therapy that could be linked to low disease reactivation. However, significant research was not conducted to further establish whether rituximab or natalizumab would be the favorable mode of therapy to suspend preconception or during the pregnancy, respectively.

Researchers conducted an observational study to compare the efficacy of rituximab suspension vs natalizumab suspension during pregnancy and 1 year post-delivery.

The researchers included 45 pregnant women between the ages of 20 and 43 at conception who suspended natalizumab amid the first trimester, as well as 37 pregnant women between the ages of 25 and 38 at conception who suspended rituximab/ocrelizumab infusion 1 year preconception, both with highly active MS. Clinical evaluations were completed at various intervals of patients’ pregnancy, comprising postconception, during pregnancy, and postdelivery.

The researchers utilized the Expanded Disability Status Scale (EDSS) to monitor disability progression, the Mann-Whitney U Test to examine demographics/disease characteristics, the Kaplan-Meier survival analysis to compare relapse rate, and the Fisher Exact Test to differentiate magnetic resonance imaging (MRI) activity.

Among the 2 groups, the researchers collected the quantity of successful births, miscarriages, and offspring malformations, as well as the relapse rates during and after pregnancy, the EDSS score monitoring disability progression, and the prevalence of no evidence of disease activity (NEDA-3).

Between the 2 groups of patients, those who suspended rituximab/ocrelizumab had analogous demographic outcomes to the natalizumab group, despite the difference in sample sizes in the study (33/37 vs 42/45 live births; 3/37 vs 3/45 miscarriages). However, the rituximab group presented 1 terminated pregnancy due to cardiac abnormality in the offspring; whereas, the natalizumab group retained 1 pregnancy, although the offspring was affected with cardiac abnormality malformation. 

Patients among the rituximab group had a lower disease relapse rate than the natalizumab group during pregnancy (1/33 [3%] vs 3/42 [7.1%]; P =.6), as well as after delivery (0/33 [0%] vs 9/42 [21.4%]; P <.01).

Moreover, the rituximab group had a smaller number of patients compared with the natalizumab group who displayed:

• gadolinium-enhanced or T2 lesions in brain or spinal cord MRI (1/31 [3%] vs 14/40 [35%]; P =.001);
• a reduced EDSS score during and after pregnancy (0/33 [0%] vs 7/42 [17%]; P =.01); and,
• a greater NEDA-3 rate (30/31 [97%] vs 21/40 [53%]; P <.001).

Although natalizumab therapy can be utilized till discontinuation at the end of the first trimester and resumed after delivery, it is not a complete successful measure for hindering disease reactivation. The continuation of natalizumab postpartum did not display significant change.

The potential of rituximab to be sustained beyond conception eliminates the need for MS treatment to be administered during and after the pregnancy, which reduces exposure to monoclonal antibodies for the newborn. Rituximab can be effective for women with highly active MS who want to conceive and achieve low disease reactivation.

“In women already receiving NTZ [natalizumab] who are planning pregnancy, the possibility to switch to RTX/OCR [rituximab/ocrelizumab] for planning pregnancy instead of maintaining NTZ until the end of the second trimester should be discussed,” the researchers concluded.

Study limitations ranged from small sample size in determining therapy safety to the absence of patients in the study who prolonged the natalizumab therapy till the conclusion of the second trimester.