Austin Health

Title
Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis.
Publication Date
2021-04-20
Author(s)
Yeh, Wei Zhen
Widyastuti, Putu Ayu
Van der Walt, Anneke
Stankovich, Jim
Havrdova, Eva
Horakova, Dana
Vodehnalova, Karolina
Ozakbas, Serkan
Eichau, Sara
Duquette, Pierre
Kalincik, Tomas
Patti, Francesco
Boz, Cavit
Terzi, Murat
Yamout, Bassem I
Lechner-Scott, Jeannette
Sola, Patrizia
Skibina, Olga G
Barnett, Michael
Onofrj, Marco
Sá, Maria José
McCombe, Pamela Ann
Grammond, Pierre
Ampapa, Radek
Grand'Maison, Francois
Bergamaschi, Roberto
Spitaleri, Daniele L A
Van Pesch, Vincent
Cartechini, Elisabetta
Hodgkinson, Suzanne
Soysal, Aysun
Saiz, Albert
Gresle, Melissa
Uher, Tomas
Maimone, Davide
Turkoglu, Recai
Hupperts, Raymond Mm
Amato, Maria Pia
Granella, Franco
Oreja-Guevara, Celia
Altintas, Ayse
Macdonell, Richard A L
Castillo-Trivino, Tamara
Butzkueven, Helmut
Alroughani, Raed
Jokubaitis, Vilija G
Type of document
Journal Article
OrcId
0000-0002-5335-6612
0000-0002-4278-7003
0000-0002-0675-2866
0000-0003-3778-1376
0000-0002-1700-1726
0000-0002-2156-8864
0000-0003-0091-0074
0000-0003-2885-9004
0000-0003-3160-9022
0000-0001-9724-851X
0000-0002-3942-4340
DOI
10.1212/WNL.0000000000012084
Abstract
To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses. We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications.
Link
Citation
Neurology 2021; online first: 20 April
Jornal Title
Neurology

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