Treatment with rituximab before or during pregnancy was not associated with major pregnancy or infant complications, according to a case series of 19 women with multiple sclerosis (MS) and other autoimmune diseases.
These findings add to the limited available evidence on the use of rituximab by expectant mothers either prior to or during pregnancy — a use strongly advised against by its manufacturer. The cases suggest that the therapy may not increase the risk of serious adverse events for either the mother or the baby.
Still, women deciding on whether to use rituximab during these periods should be aware that data collected so far are still insufficient to draw effective conclusions on rituximab’s safety, the researchers noted.
The study, “Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series,” was published in the journal Rheumatology Advances in Practice.
Rituximab is approved for the treatment of certain blood cancers and rheumatoid arthritis, a type of autoimmune disease. It is marketed as Rituxan, by Biogen, in the U.S., Canada, and Japan. In Europe, it is marketed as MabThera, by Roche’s subsidiary Genentech. Other brand names are used elsewhere.
Because it works to deplete B-cells — a type of immune cell known to be involved in autoimmune diseases — rituximab also is used off-label to treat MS and other autoimmune disorders such as juvenile idiopathic arthritis.
However, its long persistence in the body following treatment cessation, along with its ability to cross the placenta after the first trimester, have raised concerns about the therapy’s use both before and during pregnancy. The main worries are for potential B-cell depletion and an increased risk of infection in newborns.
Due to the limited data on the therapy’s safety during these periods, the manufacturer recommends avoidance of rituximab throughout pregnancy and for one year prior to conception.
Now, a team of researchers at the University of California, San Diego, have described the frequency of pregnancy and infant complications in 19 women exposed to rituximab before and/or during pregnancy.
The team analyzed data from the MotherToBaby Pregnancy Studies, which collect data on exposures to therapies of interest — and notably, pregnancy outcomes — in women living in the U.S. and Canada.
Information on treatment exposure, pregnancy complications, and the health status of infants, who are followed up to one year after birth, is collected from medical records, telephone interviews, and specialized examinations.
Here, the women — 15 with rheumatoid arthritis or juvenile idiopathic arthritis and four with MS — were enrolled in the study between 2007 and 2019. All were enrolled at a mean gestational age of 15.3 weeks, meaning they were nearly four months pregnant.
Two-thirds said they planned their pregnancies and most reported exposure to medications or substances that could affect pregnancy and infant outcomes before or during pregnancy.
Participants were divided into three groups, based on the time window of rituximab exposure: the during pregnancy group (three women), the before and during pregnancy group (three women), and the pre-pregnancy group (13 women).
Of note, women with rituximab exposure before and during pregnancy received their last dosing before conception, but had assumed pregnancy exposure due to rituximab’s long persistence. Those on rituximab prior to pregnancy had their last dosing no sooner than 14.8 weeks (more than three months) before conception.
The results showed that no miscarriages or stillbirths (fetal death after 20 weeks of pregnancy) occurred. However, there were two (10.5%) premature births, both in the pre-pregnancy group, and two (10.5%) term infants born small for gestational age — one in the pregnancy group and one in the pre-pregnancy group.
The frequencies of these events, as well as of other pregnancy complications, occurred “at or below expected rates for the general population,” the researchers wrote.
In addition, the frequency of infant complications did not appear to be high, and many of them could be explained by a co-exposure to other potentially damaging therapies or substances that the mother took during pregnancy, the team noted.
The most common infant complication was jaundice (53%), whose frequency was consistent with that reported for the general population (about 60% of newborns). Jaundice is a usually harmless condition that makes a baby’s skin, eyes, and other tissues turn yellow due to the build-up of bilirubin — a yellow substance produced when red blood cells are broken down. In most cases, no treatment is needed and the condition abates on its own.
There were no reports of serious or opportunistic infections after birth, nor of B-cell depletion in these infants.
Three infants had a major structural defect. Among them, one was born to a woman with MS exposed to the therapy before pregnancy and during the first trimester, while two were born to women in the pre-pregnancy group, one of whom had MS.
No specific pattern of minor structural defects was detected in infants undergoing specialized examination, but there were some similarities with Hoffman syndrome, a genetic condition associated with the absence of B-cells.
Given the lack of testing regarding B-cell numbers in these infants, whether these findings were associated with B-cell depletion remains unclear.
“Health-care providers who are overseeing care for infants with prenatal exposure to rituximab should consider ordering laboratory work that assesses B cell status, in an attempt to provide a more complete picture of immune function,” the researchers wrote.
The team noted that future studies also should assess long-term follow-up data of exposed infants in terms of their immune function.
Overall, “no evidence of any excess of serious adverse outcomes was seen in this small sample of children born to women who took rituximab before or during pregnancy,” the researchers concluded.
“Women who are deciding whether to continue use of rituximab in pregnancy should understand that the available data are still insufficient to document safety and recommend the use of rituximab during pregnancy, but they should be aware that no patterns of birth defects, pregnancy complications or negative infant health outcomes were observed in the small case series presented here,” the team added.
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