Long-Term Disability Linked to Prior MS Relapses in Pregnant Women

Disease Spotlight | <b>Disease Spotlight: Multiple Sclerosis</b>

Longer exposure to disease-modifying therapy over the follow-up period reduced the risk of disability worsening among pregnant people with multiple sclerosis.

For women with multiple sclerosis (MS), experiencing a disease relapse the year before conception is associated with worsened long-term disability in comparison to those without pregnancy, according to results from the Italian Pregnancy dataset.1

Senior author Maria P. Amato, MD, director, Neurological Rehabilitation Unit, and professor of neurology, Careggi University Hospital, and colleagues collected data on the risk of long-term disability in 230 pregnant patients with MS (pregnancy group; PG) and 102 control group (CG) non-pregnant patients with MS. Time to disability worsening based on Expanded Disability Status Scale (EDSS) score was assessed through a multivariate Cox regression model.

Over a follow-up period of 6.5 (±3.1) years, disability progression occurred in 87 (26.2%) women overall, 65 (28.3%) in the PG and 22 (21.6%) in the CG (P = .201). The investigators found that the risk of disability worsening was associated with relapse in pregnant women the year before conception (adjusted hazard ratio [aHR], 1.74 [95% CI, 1.06-2.84]; P = .027).

Amato et al wrote, "this finding has both research and clinical practice implications. As for the first, it strongly indicates that epidemiological studies on the prognostic role of pregnancy should take into account disease activity in the year before conception. As for counselling and management of MS women facing a pregnancy, our finding suggests a shift of attention towards the pre-pregnancy period, that is, it underscores the importance of pregnancy planning in MS.”

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In addition to previous relapses, disability worsening was associated with higher EDSS at baseline (aHR, 1.39 [95% CI, 1.12-1.74; P = .003), younger age (aHR, 0.95 [95% CI, 0.91-0.99]; P = .022) and shorter disease-modifying therapy (DMT) exposure over the follow-up (P <.008). Ongoing treatments included interferons (63 of 72) and glatiramer acetate (9 of 72) in the PG and interferons (52 of 64); and glatiramer acetate (6 of 64), azathioprine (3 of 64), mitoxantrone (2 of 64), and autologous hematopoietic stem cells transplantation (1 of 64) in the CG.

The risk of disability worsening for those in the PG was also associated with the occurrence of relapses in the post-partum year (aHR, 1.85 [95% CI, 1.11-3.06]; P = .018), and, marginally, the occurrence of relapses in the year before conception (aHR, 1.61 [95% CI, 0.94-2.77]; P = .086). Notably, patients who had longer exposure to DMTs over the follow-up period had reduced risk of disability worsening (P <.010).

Amato and colleagues noted that it is possible to speculate that pregnancy could delay treatment reintroduction and optimization rather than cause disability worsening. Postponing treatment optimization can be particularly relevant in patients with recent disease activity, leaving a period of higher vulnerability, especially in the post-partum months.

They also identified that the study was limited by the fact that it was included data gathered in the early 2000s and included only women with MS who were untreated or received platform injectable therapies. There were no women treated with fingolimod (Gilenya; Novartis) and natalizumab (Tysabri; Biogen) and information on potential maternal harms related to the suspension of treatment with these drugs was lacking. To that note, another study published in March 2020 suggested that maintaining natalizumab treatment during the first trimester may reduce the risk of disease reactivation during pregnancy compared to withdrawal of treatment at conception.2

Additional previous research published earlier this year and performed by Adi Vankin-Dembinsky, MD, PhD, senior neurologist, Hadassah Medical Center, and colleagues showed that brain MRI during the year before pregnancy can predict postpartum clinical relapses of MS. In that study, researchers found that relapses in the first 3 months postpartum were significantly correlated with an active-MRI prepregnancy (odds ratio [OR], 6.091 [95% CI, 2.3-16.13]; P <.001) and EDSS score prepregnancy (OR, 1.780 [95% CI, 1.158-.735]; P = .009).3

REFERENCES
1. Portaccio E, Tudisco L, Pasto L, et al. Pregnancy in multiple sclerosis women with relapses in the year before conception increases the risk of long-term disability worsening. Multiple Sclerosis Journal. Published online June 16, 2021. doi: 10.1177/13524585211023365
2. Demortiere S, Rico A, Maarouf A, Boutiere C, Pelletier J, Audoin B. Maintenance of natalizumab during the first trimester of pregnancy in active multiple sclerosis. Mult Scler. Published online March 23, 2020. doi: 10.1177/1352458520912637
3. Lehmann H, Zveik O, Levin N, Brill L, Imbar T, Vaknin Dembinksy A. Brain MRI activity during the year before pregnancy can predict post-partum clinical relapses. Mult Scler J. Published online March 30, 2021. doi: 10.1177/13524585211002719