Early Postpartum Period Has Highest Risk for Relapse, Expert Advises

The first three months after giving birth are a particularly high-risk time for developing neuromyelitis optica spectrum disorder (NMOSD) and for experiencing relapses when the disease is already established, an expert emphasized in a recent webinar hosted by the The Sumaira Foundation for NMO.

The pregnancy-focused webinar featured Eric Klawiter, MD, a neurologist at Massachusetts General Hospital, in Boston, and an associate professor of neurology at Harvard Medical School. This was the seventh webinar of the foundation’s series, called From the Experts, which is supported by a patient education grant from Viela Bio.

“It’s important to talk about these issues, even from the onset of starting [a] medication if you know that … at some point in the future, you would be considering starting a family,” Klawiter said.

In NMOSD, the immune system mistakenly attacks proteins in astrocytes and oligodendrocytes — cells that support the nervous system — and causing inflammation in the optic nerve and spinal cord.

The disease mainly affects women and the multiple hormonal and immunologic changes associated with pregnancy can influence the development and course of NMOSD.

However, a decade ago, when the neurologist was presented with a case of a 21-year-old who developed bilateral NMOSD shortly after giving birth, “there was very little information on what to do” and “there were lots of questions that related to neuromyelitis optica and pregnancy,” Klawiter said.

This lack of information prompted him to lead an international, retrospective study, published in 2017, aimed at shedding light on the effects of pregnancy on NMOSD onset, postpartum relapse rate, and pregnancy outcomes.

“This was a great example of the need for multiple sites, collaborating together to try to answer [these questions],” Klawiter said.

A total of 217 women with NMOSD, with a mean age of 49.5 years, were recruited at eight sites in the U.S., the U.K., and Germany. Most (79.3%) had a previous history of pregnancy, and 31 of them had a NMOSD diagnosis prior to pregnancy.

Results showed that “a high percentage” of these women (25%) developed the disease during pregnancy (10.5%) or in the postpartum period (7.9% in the first three months and 6.6% in the first six months).

Notably, about 10% of women diagnosed before the age of 40 had their symptom onset “in that first three-month postpartum period,” which was “about three times higher than what you would have expected for any … period of time,” Klawiter said.

This also was “the highest risk period for relapse” among women with a history of pregnancy after an NMOSD diagnosis, which “was really informative as we try to counsel our patients,” the neurologist said. These findings were supported by several other studies from different NMOSD patient populations around the world.

In addition, of the 46 pregnancies following symptom onset, 34 led to a live birth (73.9%), 10 resulted in spontaneous miscarriage (21.7%), and two ended in therapeutic abortion (4.3%). The rate of spontaneous miscarriage was slightly higher than the estimated 10–15% for the general population, Klawiter noted.

No significant association was found between breastfeeding — reported in about 80% of live births — and relapse rates.

Given that this and other studies suggested that women with NMOSD may have a higher risk of pre-eclampsia — high blood pressure and signs of liver or kidney damage during pregnancy — Klawiter recommended that blood pressure be closely monitored in this context.

Moreover, 31.1% of women with no history of pregnancy cited concerns about potential disease worsening or stopping disease-modifying treatments as reasons for not becoming pregnant.

This highlights the importance of gaining knowledge in this area “so that we can best inform and counsel our patients,” the neurologist said, noting that he also encourages “an interdisciplinary sort of planning and discussion” involving the patient’s neurologist, obstetrician, and primary care doctor.

Regarding the best time to think about starting a family, Klawiter emphasized that, in general, “the optimal time for pregnancy is during a period of time when you’ve had good control related to relapses,” with the relevant relapse-free time being determined for each case.

Also, treatment management before and during pregnancy may mean looking at the risk of several therapies for the fetus and considering temporarily switching to one “that might not have been your first choice, but becomes a better first choice … in the setting of pregnancy,” Klawiter said.

While NMOSD is rare and pregnancy in these patients also is less common, the effects of some of the available treatments have been assessed during pregnancy in other diseases.

One example is Soliris (eculizumab), one of the latest approved therapies for NMOSD, and therefore with few data in the setting of pregnancy in this patient population.

A previous study involving 100 women treated with Soliris for paroxysmal nocturnal hemoglobinuria — a rare, inherited blood-related disorder — during pregnancy found no adverse impact on pregnancy outcomes, Klawiter noted.

While further studies in NMOSD are needed to confirm these findings, they suggest that Soliris “may be a safe medication to use in the setting of pregnancy,” he added.

Yet, Klawiter emphasized that treatment decisions should be discussed with treating physicians based on the patient’s personal history and clinical course.

Other discussions important during the postpartum period include whether to breastfeed and when to restart treatment. If a patient has stopped treatment during pregnancy, it may be key to restart it as soon as possible to prevent potential relapses in that high-risk postpartum period, he noted.

“I will typically counsel … [that] the way to be the best mother to your newborn is just really promoting your health,” the neurologist said.