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Multicenter Study
. 2025 Sep 2;8(9):e2531581.
doi: 10.1001/jamanetworkopen.2025.31581.

Pregnancy-Related Disease Outcomes in Women With Moderate to Severe Multiple Sclerosis Disability

Jessica Shipley  1   2 , Heidi N Beadnall  3 , Paul G Sanfilippo  1 , Wei Zhen Yeh  1   2 , Dana Horakova  4 , Eva Kubala Havrdova  4 , Pavel Hradilek  5 , Tomas Kalincik  6   7 , Izanne Roos  6   7 , Alexandre Prat  8 , Marc Girard  8 , Zuzana Rous  9 , Zbysek Pavelek  10 , Oliver H H Gerlach  11   12 , Jeannette Lechner-Scott  13   14 , Raed Alroughani  15 , Serkan Ozakbas  16   17 , Marek Peterka  18 , Katherine Buzzard  19   20 , Olga G Skibina  2   19   20 , Davide Maimone  21 , Matteo Foschi  22   23 , Andrea Surcinelli  22 , Rana Karabudak  24   25 , Daniele L A Spitaleri  26 , Alessandra Lugaresi  27   28 , Valentina Tomassini  29   30   31 , Riadh Gouider  32   33 , Saloua Mrabet  32   33 , Beatriz Romero Ferrando  34 , Suzanne Hodgkinson  35 , Pavel Štourac  36 , Joana Guimarães  37 , Nevin A John  38   39 , Richard A L Macdonell  40 , Jose E Meca-Lallana  41   42 , Helmut Butzkueven  1   2 , Anneke van der Walt  1   2 , Vilija G Jokubaitis  1   2 ; MSBase Investigator Group
Collaborators, Affiliations
Multicenter Study

Pregnancy-Related Disease Outcomes in Women With Moderate to Severe Multiple Sclerosis Disability

Jessica Shipley et al. JAMA Netw Open. .

Abstract

Importance: Understanding the association between pregnancy and clinical outcomes in women with moderate to severe multiple sclerosis (MS) disability is crucial for guiding family planning and management strategies.

Objective: To assess peripregnancy relapse activity and disability progression in women with a preconception Expanded Disability Status Scale (EDSS) score of 3 or higher.

Design, setting, and participants: This multicenter retrospective cohort study used data from the MSBase Registry, with clinical observations spanning 1984 through 2024. Study cohorts included pregnant women with MS with a preconception EDSS score of 3 or higher (range: 3-10, with higher scores indicating more severe MS-related disability) and propensity score-matched nonpregnant women with MS (controls).

Main outcomes and measures: The main outcomes were peripregnancy annualized relapse rates (ARRs) and time to 6-month confirmed disability worsening (CDW).

Results: A total of 1631 women with MS were included, of whom 575 were in the pregnant cohort (median [IQR] age at pregnancy, 32.5 [29.1-36.1] years) and 1056 were in the nonpregnant cohort (median [IQR] age, 32.6 [27.5-37.2] years). The median (range) preconception EDSS score was 3.5 (3.0-7.5). Relapse activity decreased during pregnancy, with a 75% reduction in ARR during the first trimester (rate ratio [RR], 0.25; 95% CI, 0.15-0.43), and increased to 36% above preconception levels in the first 3 months post partum (RR, 1.36; 95% CI, 1.06-1.75). Relapse during pregnancy was associated with a higher preconception ARR (odds ratio [OR], 1.56; 95% CI, 1.10-2.20) and preconception use of natalizumab (OR, 4.42; 95% CI, 1.24-23.57) or fingolimod (OR, 14.07; 95% CI, 2.81-91.30). Older age (OR, 0.92; 95% CI, 0.85-0.99) and continuation of disease-modifying therapy into pregnancy (OR, 0.42; 95% CI, 0.19-1.00) were associated with reduced risk. Disease-modifying therapy reinitiation within 1 month post partum was associated with lower odds of early postpartum relapse (OR, 0.45; 95% CI, 0.23-0.86). There was no significant difference in time to CDW between the pregnant and nonpregnant groups (hazard ratio [HR], 1.15; 95% CI, 0.96-1.38). However, ARR during pregnancy (HR, 1.37; 95% CI, 1.13-1.65) and postpartum EDSS score higher than 4 (HR, 2.69; 95% CI, 1.80-4.03) were associated with shorter time to CDW.

Conclusions and relevance: In this cohort study, women with moderate to severe MS disability exhibited a pattern of peripregnancy relapse activity similar to that reported in women with less disability. Pregnancy was not associated with worse long-term disability outcomes, although optimizing disease control in the peripregnancy period remained critical.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Shipley reported receiving a Research Training Program stipend scholarship at Monash University from the Australian government during the conduct of the study. Dr Beadnall reported receiving educational travel support from Merck and Novartis and personal fees from Roche, Novartis, and Biogen outside the submitted work. Dr Yeh reported receiving personal fees from Merck and Novartis; travel support from UCB; and research support from the European Committee for Treatment and Research in Multiple Sclerosis and RACP Foundation outside the submitted work. Dr Horakova reported receiving grants from First Faculty of Medicine Charles University and General University Hospital in Prague during the conduct of the study and personal fees from Merck, Sanofi, Roche, and Biogen outside the submitted work. Prof Havrdova reported receiving personal fees from Sanofi AB, Roche, Johnson & Johnson AB, Merck AB, and Novartis outside the submitted work. Prof Kalincik reported receiving personal fees from MS International Federation and World Health Organization, Therapeutic Goods Administration, BMS, Roche, Janssen, Genzyme, Novartis, Merck, and Biogen; conference travel support and/or speaker honoraria from WebMD Global, Merck, Sandoz, Novartis, Biogen, Roche, Eisai, Genzyme, Teva, and BioCSL; and research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck outside the submitted work. Dr Roos reported receiving grants from National Health and Medical Research Council (NHMRC) and personal fees from Merck, Novartis, and Roche outside the submitted work. Prof Lechner-Scott reported receiving grants from Merck, personal fees from Merck, and personal fees from Novartis outside the submitted work. Dr Alroughani reported receiving personal fees from Roche, Novartis, AstraZeneca, Merck, Biogen, and Sanofi outside the submitted work. Dr Peterka reported receiving personal fees from Merck, Novartis, Biogen, Sanofi-Genzyme, Janssen-Cilag, Teva, Roche, and Bristol-Myers Squibb. Dr Buzzard reported receiving personal fees from Biogen, Roche, Merck, Sanofi, and Novartis during the conduct of the study and personal fees from Alexion, UCB, and Argenx outside the submitted work. Dr Maimone reported receiving personal fees from Biogen, Merck, Novartis, Roche, Sanofi, and Alexion outside the submitted work. Dr Foschi reported receiving personal fees from Roche, Novartis, Merck, Sanofi, Biogen, and Bristol-Myers Squibb during the conduct of the study. Dr Lugaresi reported receiving grants from Novartis and Roche and personal fees from Alexion, Amgen/Horizon, Biogen, Bristol-Myers Squibb/Celgene, Merck Serono, Novartis, Roche, Sanofi/Genzyme, and Janssen/Johnson & Johnson outside the submitted work. Prof Tomassini reported receiving personal fees from Roche, Novartis, Viatris, Amgen, Merck, Bristol-Myers Squibb, Janssen, Alexion, Horizon, and Biogen outside the submitted work. Dr John reported being a PI on MS commercial studies sponsored by Roche, Novartis, Sanofi-Genzyme, and Biogen and receiving personal fees from Merck and Novartis outside the submitted work. Dr Meca-Lallana reported receiving personal fees from Almirrall, Biogen, Neuraxpharm, and Sandoz; grants from Biogen and UCB; nonfinancial support, personal fees, and grants from Bristol-Myers Squibb, Merck, Novartis, Roche, and Sanofi; and nonfinancial support and personal fees from Johnson & Johnson outside the submitted work. Prof Butzkueven reported receiving support to institution from Roche and Merck; service agreement fees to institution from Novartis, Merck, Biogen, and UCB; travel support from Novartis and Merck; and personal fees from Merck, Novartis, and Roche outside the submitted work. Dr Van der Walt reported receiving personal fees from Novartis, Roche, and Merck; grants, travel support, and personal fees from MS Australia; grants from NHMRC; and personal fees as Chief Operating Officer from MSBase Foundation outside the submitted work. Dr Jokubaitis reported receiving grants from NHMRC, MS Australia, Australian Medical Research Future Fund, F. Hoffman La-Roche, and Pennycook Foundation and personal fees from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Annualized Relapse Rates (ARRs) and Rate Ratios (RRs) for Live Births
RRs were calculated using a mixed-effects Poisson regression model. Error bars represent 95% CIs.
Figure 2.
Figure 2.. Annualized Relapse Rate (ARR) Ratios Relative to the Preconception Year by Disease-Modifying Therapy (DMT) and Treatment Epoch
Rate ratios, calculated using a mixed-effects Poisson regression model, and 95% CIs for each categorical variable are detailed in eTable 4 in Supplement 1. Corresponding absolute ARR plots are included in eFigure 6 in Supplement 1. Anti-CD20 therapy included ocrelizumab (n = 25) or rituximab (n = 6). Early epoch was defined as before 2005, middle epoch as between 2005 and 2010, and modern epoch as after 2010. Error bars represent 95% CIs.
Figure 3.
Figure 3.. Kaplan-Meier Survival Curves by Pregnancy History
CDW indicates confirmed disability worsening.
See this image and copyright information in PMC

References

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