In view of practically relevant results from this year’s ECTRIMS meeting, I would like to emphasize studies on pregnancy and breastfeeding. B-cell-depleting therapies such as ocrelizumab and ofatumumab are often used in women of childbearing age. Unfortunately, the product information for ocrelizumab (Ocrevus) for women of childbearing age indicates that contraception should be used during treatment with ocrelizumab and for 12 months after the last infusion. For a medication that is infused every 6 months, this is not a sensible recommendation if there is a desire to have children. The product information for the newer ofatumumab, which is injected subcutaneously monthly, also recommends contraception for 6 months after the last injection. Therefore, currently “officially” a pregnancy under B-cell depleting therapies is not possible.
However, this is an untenable situation. On the one hand, because most pregnancies occur unplanned. On the other hand, because highly effective B-cell depletion is needed by many patients (more or less without alternative) to control MS.
Therefore, it is significant to approach this topic scientifically. And to generate data that clarify whether the administration of B-cell-depleting therapies in women of childbearing age presents a problem and how the desire to have children can be sensibly realized under a B-cell-depleting therapy. Several research groups have worked on this important topic in recent years and presented their results at the ECTRIMS Meeting 2022.
Carolin Schwanke from the working group of Kerstin Hellwig (Bochum) analyzed the clinical data of 49 children who were potentially exposed to a B-cell-depleting (anti-CD20) therapy during pregnancy. The time between the last menstruation and anti-CD20 exposure was on average 50 days when the therapy was given before pregnancy and 44 days when the therapy was given during pregnancy. Fortunately, there were no malformations or serious infections up to one year after birth. The exposure also had no relevant influence on B-cell physiology. Only with exposure in the 2nd or 3rd trimester was there a reduction in the child’s B-cells, which quickly recovered. The authors therefore conclude that anti-CD20 therapies are safe in women of childbearing age and conception can be planned shortly after the last infusion/injection.
This view is supported by the evaluation of the pregnancy registry of Roche company with regard to ocrelizumab. The data were presented by Celia Oreja-Guevara (Madrid) and are based on the evaluation of a total of 2020 pregnancies, 35% of which had in utero exposure to ocrelizumab. Of the 532 prospectively followed pregnancies with in utero exposure, the course is known for 286 pregnancies: 225 (78.7%) normal live births; 4 (1.4%) ectopic pregnancies; 33 (11.5%) therapeutic or elective abortions; 23 (8.0%) spontaneous abortions; 1 (0.3%) stillbirth. In view of these numbers, no relevant safety aspects arise.
Finally, the evaluations of 59 pregnancies and the transfer of anti-CD20 antibodies into breast milk, presented by Annika Anderson (San Francisco), are of great practical interest. Although a transfer into breast milk could be detected, this was with a so-called Relative Infant Dose (RID) of < 1%. In general, a RID of < 10% is considered acceptable. Along with the low bioavailability of monoclonal antibodies when taken orally, a child’s risk from breastfeeding under anti-CD20 therapy can be ruled out with high probability. In addition, no signs of developmental delay in the children were found later.
In summary, these data provide important clues on how to realize the desire to have children under therapy with ocrelizumab and other B-cell-depleting therapies. It does not seem to be a problem to plan a pregnancy shortly after the last anti-CD20 administration. Unplanned pregnancies under anti-CD20 therapy represent a calculable risk in view of the data. After giving birth, mothers can be advised to breastfeed their children shortly after resuming anti-CD20 therapy.
