Monoclonal Antibodies in Pregnancy and Breastfeeding in Patients with Multiple Sclerosis: A Review and an Updated Clinical Guide

Abstract

The use of high-efficacy disease-modifying therapies (DMTs) early in the course of multiple sclerosis (MS) has been shown to improve clinical outcomes and is becoming an increasingly popular treatment strategy. As a result, monoclonal antibodies, including natalizumab, alemtuzumab, ocrelizumab, ofatumumab, and ublituximab, are frequently used for the treatment of MS in women of childbearing age. To date, only limited evidence is available on the use of these DMTs in pregnancy. We aim to provide an updated overview of the mechanisms of action, risks of exposure and treatment withdrawal, and pre-conception counseling and management during pregnancy and post-partum of monoclonal antibodies in women with MS. Discussing treatment options and family planning with women of childbearing age is essential before commencing a DMT in order to make the most suitable choice for each individual patient.

Evaluating the Therapeutic Potential of Ublituximab in the Treatment of MS: Design, Development and Place in Therapy

“…Real-world data for rituximab, ocrelizumab and ofatumumab suggest that due to the high molecular weight of mAbs, concentrations in breast milk are low or undetectable and that anti-CD20 mAbs are generally considered safe during breastfeeding. 32 This is reflected in expert guidelines. 33 …”

“…It is, however, expected to have similar characteristics to other anti-CD20 mAbs, for which real-world registry data are published. 32 , 33 …”

“…The half-life of ublituximab is 21.8 days, so complete clearance (five half-lives) should occur by point of placental transfer (weeks 17–22 gestation). 32 Fetal exposure should therefore be minimal, even if the last infusion was just prior to conception. Current recommendations from the manufacturer (TG Therapeutics) are for female patients who have received ublituximab to use effective contraception for six months following the last dose.…”

“…However, it is anticipated that no harm would be caused to the fetus if the last infusion occurred closer to conception date due to the lack of placental transfer of mAbs in earlier stages of pregnancy, as with other anti-CD20 mAbs. 32 As such, expert guidelines regarding family planning and ublituximab are likely to mirror other anti-CD20 mAbs currently used in MS clinical practice. 33 …”