Abstract
Anti-CD20 monoclonal antibodies (anti-CD20-mAbs) are known to be actively transported over the placental barrier from the 22nd gestational week (gw) on. Given a plasma half-life time between 30 (rituximab), 26 (ocrelizumab), and 16 days (ofatumumab), the transfer of relevant amounts of the drug is unlikely when treatment is stopped shortly before pregnancy. However, the pregnancy label recommends cessation 6–12 months prior to conception.
Major concern of exposure during pregnancy is not teratogenicity but a higher number of preterm birth 1 or B-cell depletion/reduction2–4 in the newborn. Late onset neutropenia is a rare complication of anti-CD20-mAbs exposure in adults and has only been reported in one newborn with rituximab (among other chemotherapeutics) in utero exposure 5 and by Caldito et al. 6 after rituximab exposure in gw 36. In this case, rituximab was given in a neuromyelitis optica spectrum disorder (NMOSD) patient without clinical symptoms but with increasing B-cell counts. The newborns B-cell counts at birth were not reported.
Although, due to the cycling dosing scheme and the long-lasting effect, anti-CD20-mAbs seem to be an elegant therapeutical option for women with NMOSD seeking pregnancy, two main questions remain: (1) Are newborns exposed during second or third trimester more susceptible for neutropenia than adults and are there other risks for adverse pregnancy outcomes or health of the newborn? (2) What predicts relapses and disability in pregnant women with NMOSD? As long as these questions are not resolved, we suggest to counsel women to conceive shortly after treatment with anti-CD20-mAbs and to restart shortly after birth—but reinfuse during late pregnancy only if critically needed. If done so, the newborns blood cell and B-cell counts should be measured immediately after birth, which underscores the need for an improvement of postnatal care of newborns with in utero anti-CD20-mAbs exposure considering a potential long-term impact on immunological development and response to vaccination.
Footnotes
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.T. received speakers honoraria from Bayer Healthcare and Biogen GmbH, payment for manuscript writing from HEXAL AG as well as sponsorship for congress participation from Biogen GmbH. K.H. has received speaker honoraria and research support from Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, Roche, and Teva; has received support for congress participation from Bayer, Biogen, Merck, Roche, Sanofi Genzyme, and Teva; and has served on scientific advisory boards for Bayer, Biogen, Sanofi, Teva, Roche, Novartis, and Merck.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
