Study Finding: Discontinuation of Natalizumab for Pregnancy Carries Risk of Disability

German research team finds that 11% of those who quit the drug for pregnancy had “clinically meaningful disability” one-year postpartum. They don’t advise against quitting the drug but say their findings suggest that patients should be informed of the risk.

While the physical effects of multiple sclerosis are challenging for all multiple sclerosis (MS) patients, they can be particularly challenging for pregnant women. Muscle weakness and coordination problems may increase the risk of falling. There is also a chance of serious fatigue. If the pregnant person with MS is dependent on a wheelchair, the risk of urinary tract infections may increase.

But how pregnancy may affect the pathophysiology of MS is not entirely clear. A number of studies suggest that pregnancy is associated with a decrease in the demyelination of neurons in the central nervous system that characterizes MS and the postpartum period with an increase.

Complicating the question of whether pregnancy is protective is MS treatment and how discontinuing medication increases the risk of a relapse.

Results of a study recently reported in JAMA Network Open showed that about 11% of the pregnant people with MS who stopped taking natalizumab — sold under Tysabri and other brand names — had significant relapse-related disability a year after giving birth.

The researchers’ analysis found that neither restarting the drug shortly after delivery nor breastfeeding was associated with protection against disability, although there was evidence the restarting in the postpartum period might help fend off some relapses (it lowered the annualized relapse rate, a measure an MS patient's average number of attacks per year).

But the German research team led by Kerstin Hellwig, M.D., did not rule out people who are pregnant who have MS quitting natalizumab. Their takeaway is that the findings suggest that they be informed about the risk. They also call for more research,

MS relapse and disability progression risk during pregnancy and postpartum is higher in women who received natalizumab before pregnancy, Hellwig wrote. “Case reports of severe disease reactivation and rebound up to death in the context of pregnancy planning have been reported. These cases are concerning, yet the magnitude of this risk is still unknown,” wrote Hellwig and her colleagues.

As a result, the researcher set out to better understand whether natalizumab cessation before or during the first trimester of pregnancy is associated with MS relapse occurrence and relapse-related disability. The study included 255 women with 274 pregnancies. In 85 of those pregnancies, the women stopped taking natalizumab before they were pregnant. In the 189 other pregnancies, they stopped taking the drug during the first trimester.

During pregnancy and the postpartum year, relapses were reported in two-thirds of the pregnancies (183 of 274), severe relapses in about 1 in 6 (44 of 274) and and potentially life-threatening relapses in three pregnancies, according to the findings that Hellwig and her team reported in the Jan. 24, 2022, issue of JAMA Network Open.

They also found that a higher proportion of women who stopped taking natalizumab before pregnancy (41 of 85, or 48%) had at least one relapse than those who stopped taking the drug during the first trimester (69 of 189, or 36%).

The timing of when the women who quit natalizumab during the first trimester also seemed to make a difference. Hellwig and her team found that the 67 women who quit the drug after they were pregnant who didn’t have relapses stopped taking natalizumab earlier in the first trimester compared with those who experienced relapses.

The risk of any relapse in Hellwig and team’s study was similar to that of smaller studies of natalizumab withdrawal for pregnancy (39.8% vs 29%-36.5%).

Another finding from the study was that pregnancy did not reduce the risk of relapse even after accounting for other risk factors. This finding is new, the researchers note, as previous studies did not model pregnancy as a time-dependent covariate,” they wrote.