These study results highlight the interest in immunosuppressive therapy taken before or during pregnancy and to reduce the risk of relapse during pregnancy and 1 year postpartum.
Data collected from a retrospective multicenter study of patients with neuromyelitis optica spectrum disorder (NMOSD) showed a lower annualized relapse rate (ARR) during pregnancy in each serostatus group, and a higher ARR during the postpartum period when compared to the prepregnancy period in patients who are aquaporin-4 (APQ4) positive.
Senior author Jerome de Seze, PhD, head, Neuroimmunological Department, University of Strasbourg, and colleagues analyzed the effects of pregnancy on NMOSD according to patients’ serostatus and immunosuppressive therapy (IST). Patients were tested for APQ4 and myelin oligodendrocyte glycoprotein (MOG) antibodies (Ab). Informative pregnancies were defined as all pregnancies occurring after the onset of NMOSD and all pregnancies when the disease presented during the pregnancy or within 12 months after delivery or abortion.
Eighty-nine informative pregnancies in 58 patients with NMOSD were included in the study. Of these, 46 (51.5%) were AQP4-Ab-positive, 30 (34%) were MOG-Ab-positive, and 13 (14.5%) were double-negative. No patients were identified as positive for both MOG-Ab and AQP4-Ab within this cohort. In total, 73 relapses were observed in 89 pregnancies, 8 (11%) of which occurred during pregnancy and were inaugural of NMOSD, while 33 (45%) occurred during first trimester postpartum (PP1), 13 (18%) during second trimester postpartum (PP2), and 19 (26%) between 6 and 12 months postpartum.
In patients with pregnancy after NMOSD onset, Seze et al documented a lower ARR during pregnancy in each serostatus group and higher ARR during the postpartum period among those who were AQP4-Ab-positive (P <.01) when compared to the prepregnancy period. Additionally, a significant rebound of ARR was observed during the first trimester postpartum in a similar manner regardless of serostatus.
In the 12 months preceding pregnancy, the mean ARR (0.70 [±0.97]) was significantly lower than the ARR in the period from disease onset to pregnancy (0.78 [±0.60]; P = 0.01). Within a subset of 22 pregnancies for which NMOSD onset occurred during the pregnancy or PP1, relapses were more frequent in PP1, represented with a mean ARR of 0.85 (±0.38), which was similar among the serogroups (P = .11).
"It seems essential to supervise the pregnancy of patients with NMOSD in order to propose an IST before conception, which will then be continued during pregnancy, especially in AQP4-Ab-positive patients. Our recommended treatment is azathioprine because its safety has already been demonstrated during pregnancy and lactation, but other options such as rituximab, eculizumab, cyclosporine, and corticosteroids may also be of interest,” the study authors wrote.
Azathioprine was the most frequent drug used during pregnancy (n = 26), alone or combined with oral steroids, followed by oral steroids alone. Pregnancy occurred under rituximab in 4 patients but was stopped 3 months before conception in 2 patients, during the trimester of pregnancy in 1 patient, and infused during pregnancy in 1 patient. Use of medication was more often in AQP4-Ab-positive patients (66%) than MOG-Ab-positive (16%) and double-negative patients (30%).
Relapses occurred in 40% (27 of 67) pregnancies occurring after the disease onset. Of these 27 pregnancies, 19 (70%) were pregnancies occurring off medication. Notably, fewer relapses occurred in pregnancies on medication (n = 8; 26%) than in pregnancies off medication (n = 19 [53%]; P = .04). AQP4-Ab-positive patients who were off medication had significantly more relapses than those on medication during pregnancy and the 1-year postpartum period (P = .02).
Ten (11%) miscarriages were reported among 89 pregnancies, almost exclusively in AQP4-Ab-positive patients (9 of 46), and 1 patient with antiphospholipid antibodies. Six (60%) miscarriages occurred in patients on IST, all with AQP4-Ab. Notably, only 1 miscarriage occurred in the following weeks after a relapse. The investigators wrote that this is a “result that could be explained by the relatively high age of these patients at the time of pregnancy, their history of autoimmunity and previous miscarriages, but also the intrinsic effect of AQP4-Ab on the placenta.”
Three (2%) patients experienced preeclampsia and 2 of them were AQP4-Ab-positive, but neither of these cases resulted in miscarriage. Investigators also concluded that the occurrence of miscarriage or preeclampsia was not influenced by medication (P = 0.21).
Treatment was stopped in 11 of the 31 (35%) pregnancies in patients on medication and was maintained in the remaining 20 (65%) cases. A trend in the data showed an increase in the number of relapses for those who stopped their treatment.