SPECIAL REPORT
Pregnancy and MS
Effect of treatment on postpartum relapses
Pregnancy outcomes in treated patients
Fetal and neonate drug exposure with ocrelizumab
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Pregnancy and MS
A decade ago the Pregnancy in Multiple Sclerosis (PRIMS) study reported that pregnancy does not appear to worsen and may benefit the clinical course of MS (Houtchens MK. Semin Neurol 2007;27:434-441). This was supported by three longitudinal studies presented at ECTRIMS 2024. The first study analysed data for 117 pregnant women with MS and reported that 70% did not experience EDSS worsening in the three years following pregnancy (Aslan et al. ECTRIMS 2024;P1241). Similarly, a five-year retrospective study found that while there was a higher relapse rate postpartum, there were no differences in EDSS score or MRI activity at three and five years after childbirth compared to non-pregnant MS controls (Ozcelik et al. ECTRIMS 2024;P903).
The BARLO MS Centre in Toronto examined pregnancy outcomes in 148 women (298 pregnancies) stratified by lower (EDSS <2) versus higher (EDSS >2) disability level (MacIsaac et al. ECTRIMS 2024;P095). The relapse rate at all time periods was numerically higher in women with a higher level of disability but there was no difference in relapse trajectory between the two groups.
A transient rise in serum neurofilament-light chain (sNfL) postpartum has been documented in women with MS, suggesting ongoing subclinical tissue damage (Proschmann et al. Front Immunol 2021:12:715195). But this may have been a misinterpretation. A similar observation has been reported in women without MS (Bertolotto et al. ECTRIMS 2024;P1830). Median sNfL levels increased from 9.2 pg/mL pre-pregnancy to 18.9 pg/mL on day 1 postpartum, and 28.0 pg/mL on days 6-10 postpartum. There were no changes in serum levels of glial fibrillary acidic protein or tau following childbirth. sNfL increased regardless of delivery method but showed a different pattern for vaginal versus Caesarean-section delivery. The authors concluded that sNfL changes reflect brain plasticity mechanisms and histological modifications following childbirth.
Effect of treatment on postpartum relapses
An important challenge in clinical practice is the timing of DMT dosing to reduce the relapse risk during pregnancy while minimizing fetal drug exposure. Two studies at ECTRIMS presented data on the impact of DMTs on relapses during pregnancy. A 10-year retrospective chart review of 194 patients on DMTs prior to pregnancy reported a significant reduction in postpartum relapses in the group receiving anti-CD20 therapy (Shah et al. ECTRIMS 2024;P093). A separate study of patients reported a lower risk of postpartum relapses in patients on high-efficacy DMTs (Lapevandani et al. ECTRIMS 2024;P1788). The relapse rate was 9.4% during pregnancy and 18.8% in the one year postpartum. All relapses occurred during an extended washout period or in patients who had discontinued treatment.
An analysis of 13 ocrelizumab trials examined disease activity before, during and after pregnancy (N=103) (Vukusic et al. ECTRIMS 2024;P591). The median time from ocrelizumab infusion to last menstrual period was 4.2 months. The median annualized relapse rate was 0.06 prior to pregnancy (n=101), 0.03 during pregnancy (n=103) and 0.04 in the year postpartum (n=81). The proportion of women with relapses was 5.9% prepregnancy, 1.9% during pregnancy and 2.5% in the year postpartum.
Similar results were found in an analysis of live births (N=208) in the Canadian database of ocrelizumab-treated patients (Krysko et al. ECTRIMS 2024;P1240). The median age at last menstrual period was 31.7 years. The median time from ocrelizumab infusion to last menstrual period was 3.3 months; the proportion with known in utero drug exposure was 40.9%. The median time from childbirth to re-starting ocrelizumab was 2.1 months. The relapse rate remained low prior to pregnancy (1.0%), during pregnancy (0%) and in the one year postpartum (1.9%). A total of 19.2% of patients experienced at least one infection.
Pregnancy outcomes in treated patients
Several large database analyses reported on pregnancy outcomes in women with MS. The German MS and Pregnancy Registry (N=3722) examined pregnancy outcomes stratified by DMT exposure (Bast et al. ECTRIMS 2024;O090). There were no differences between the DMT-exposed and unexposed group with respect to spontaneous abortion, preterm birth or major congenital abnormalities. Severe infections during pregnancy were more frequent in patients receiving an S1PR modulator (odds ratio 3.03), a fumarate (OR 2.64) or natalizumab during the third trimester (OR 2.56). Antibiotic use was more common in women exposed to natalizumab in the second trimester (OR 2.32), an anti-CD20 agent (OR 1.82) or an S1PR modulator (OR 1.53). Birth weight was significantly lower in those exposed to an S1PR modulator or to natalizumab in the third trimester. Neonates small for gestational age (SGA) were most common in the S1PR and anti-CD20 groups. The overall SGA rate was 19.2% for DMT-exposed versus 17.6% for DMT-unexposed patients compared to 10.0% for the general population. In addition, a descriptive analysis found a higher rate of severe infections during pregnancy with alemtuzumab (9.1%) and a higher rate of preterm births with teriflunomide (21.9%). The rate of major congenital abnormalities was 12.0% with teriflunomide and 10.5% with alemtuzumab.
A retrospective study (N=15) reported the results of the NAP-30 protocol used to treat women with highly-active MS during pregnancy (Lopez et al. ECTRIMS 2024;P1235). Patients received natalizumab every six weeks during the first 30 weeks of pregnancy. The mean number of natalizumab doses prior to pregnancy was 40.3. Sixteen of 19 pregnancies were full-term; there were three spontaneous abortions. There was one elective preterm delivery at week 35 after moderate anemia was detected; low birth weight and anemia resolved within two months. The other infants had normal birth weight and no blood count abnormalities. All infants demonstrated normal development. There were no relapses or new MRI lesions at six months postpartum.
Fetal and neonate drug exposure with ocrelizumab
Also noteworthy were two studies that investigated anti-CD20 exposure during pregnancy and breastfeeding. The phase IV MINORE study enrolled 35 women with CIS/MS who had received ocrelizumab <6 months prior to the last menstrual period (Hellwig et al. ECTRIMS 2024;P087). Ocrelizumab was undetectable in 68.6% of women at weeks 24-30, 94.1% at week 35, and 97.1% at delivery. Ocrelizumab was undetectable in 94.3% of umbilical cord samples and 97.0% of infant serum samples. In utero ocrelizumab exposure was not associated with B cell depletion: B cell levels were above the age-specific lower limit of normal in all infants. In the neonate group there were five serious adverse events that were not considered to be related to ocrelizumab.
The phase IV SOPRANINO study (N=13) examined ocrelizumab pharmacodynamics in infants during breastfeeding (Bove et al. ECTRIMS 2024;O039). The mean time to re-starting ocrelizumab was two months postpartum. Infant blood samples were obtained one month post-infusion. The average daily infant dose (ADID) of ocrelizumab exposure was 45.1 µg; the average relative infant dose was 0.3%. Ocrelizumab was undetectable in all neonate serum samples. B cell levels were within the normal range for all infants. A total of 76.9% of infants experienced an infection. The authors concluded that health outcomes were consistent with common childhood illnesses in the first year of life. Future analyses will evaluate infant growth and humoral response to vaccination.
Quick poll on pregnancy and MS