TY - JOUR
T1 - Natalizumab, Fingolimod, and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis
AU - Yeh, Wei Zhen
AU - Widyastuti, Putu Ayu
AU - Van der Walt, Anneke
AU - Stankovich, Jim
AU - Havrdova, Eva
AU - Horakova, Dana
AU - Vodehnalova, Karolina
AU - Ozakbas, Serkan
AU - Eichau, Sara
AU - Duquette, Pierre
AU - Kalincik, Tomas
AU - Patti, Francesco
AU - Boz, Cavit
AU - Terzi, Murat
AU - Yamout, Bassem I.
AU - Lechner-Scott, Jeannette
AU - Sola, Patrizia
AU - Skibina, Olga G.
AU - Barnett, Michael
AU - Onofrj, Marco
AU - Sá, Maria José
AU - McCombe, Pamela Ann
AU - Grammond, Pierre
AU - Ampapa, Radek
AU - Grand'Maison, Francois
AU - Bergamaschi, Roberto
AU - Spitaleri, Daniele L.A.
AU - Van Pesch, Vincent
AU - Cartechini, Elisabetta
AU - Hodgkinson, Suzanne
AU - Soysal, Aysun
AU - Saiz, Albert
AU - Gresle, Melissa
AU - Uher, Tomas
AU - Maimone, Davide
AU - Turkoglu, Recai
AU - Hupperts, Raymond M.M.
AU - Amato, Maria Pia
AU - Granella, Franco
AU - Oreja-Guevara, Celia
AU - Altintas, Ayse
AU - Macdonell, Richard A.
AU - Castillo-Trivino, Tamara
AU - Butzkueven, Helmut
AU - Alroughani, Raed
AU - Jokubaitis, Vilija G.
AU - on behalf of the MSBase Study Group
N1 - Funding Information:
Funding provided by the NHMRC of Australia, grant 1156519; Multiple Sclerosis Research Australia Postgraduate Scholarship, No. 19-0735; and Australian Government Research Training Program Scholarship. MSBase is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer-Schering, Sanofi Genzyme, and Teva.
Funding Information:
Funding provided by the NHMRC of Australia, grant 1156519; Multiple Sclerosis Research Australia Postgraduate Scholarship, No. 19-0735; and Australian Government Research Training Program Scholarship. MSBase is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer-Schering, Sanofi Genzyme, and Teva.
Funding Information:
W.Z. Yeh reports research support from Multiple Sclerosis Research Australia and the Australian Government Research Training Program during the conduct of the study, as well as speaker honoraria and conference attendance support from Biogen and travel support from Merck, outside of the submitted work. P.A. Widyastuti, A. Van der Walt, J. Stankovich, and E. Havrdova report no disclosures. D. Horakova received compensation for travel, speaker honoraria, and consultant fees from Biogen, Novartis, Merck, Bayer, Sanofi, Roche, and Teva, as well as support for research activities from Biogen and support by the Czech Ministry of Education project Progress Q27/LF1. K. Vodehnalova received compensation for traveling, conference fees, and consulting fees from Merck, Teva, Sanofi Genzyme, Biogen Idec, Novartis, and Roche S. Ozakbas reports no disclosures S. Eichau received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva P. Duquette reports no disclosures. T. Kalincik served on scientific advisory boards for Roche, Sanofi Genzyme, Novartis, Merck, and Biogen and steering committee for Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL, and Merck; and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck. F. Patti received personal compensations for talks and serving on advisory boards by Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva and received research grants from Biogen, Merck, Fondazione Italiana Sclerosi Multipla, Reload Onlus Association, and University of Catania. C. Boz, M. Terzi, and B.I. Yamout report no disclosures. J. Lechner-Scott has accepted travel compensation from Novartis, Biogen, Roche, and Merck. Her institution receives the honoraria for talks and advisory board commitment as well as research grants from Biogen, Merck, Roche, Teva, and Novartis. P. Sola, O.G. Skibina, M. Barnett, M. Onofrj, M.J. Sá, P.A. McCombe, P. Grammond, R. Ampapa, F. Grand'Maison, R. Bergamaschi, and D.L.A. Spitaleri report no disclosures. V. Van Pesch has received travel grants from Merck, Biogen, Sanofi, Celgene, Almirall, and Roche. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Celgene, Merck, and Novartis Pharma. E. Cartechini received speaker honoraria and travel grants from Novartis, Roche, and Sanofi-Genzyme. S. Hodgkinson and A. Soysal report no disclosures. A. Saiz received compensation for consulting services and speaking honoraria from Merck-Serono, Biogen Idec, Sanofi-Aventis, Teva, Roche, Novartis, and Alexion. M. Gresle reports no disclosures. T. Uher received financial support for conference travel and honoraria from Biogen Idec, Novartis, Roche, Genzyme, and Merck Serono, as well as support for research activities from Biogen Idec and Sanofi. D. Maimone received speaker honoraria for advisory board and travel grants from Almirall, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. R. Turkoglu, R.M.M. Hupperts, M.P. Amato, and F. Granella report no disclosures. C. Oreja-Guevara received personal compensations for talks and serving on advisory boards from Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. A. Altintas and R.A. Macdonell report no disclosures. T. Castillo-Triviño received speaking/consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. H. Butzkueven's institution received compensation for advisory board, steering committee, and educational activities from Biogen, Roche, Merck, and Novartis. His institution received research support from Roche, Novartis, Biogen, NHMRC, Medical Research Future Fund Australia, and MS Research Australia. He received personal compensation from Oxford HPF for serving on the steering group of MS Brain Health. R. Alroughani reports no disclosures. V.G. Jokubaitis received conference travel support from Merck and Roche and speaker’s honoraria from Biogen and Roche outside of the submitted work. She receives research support from the Australian National Health and Medical Research Grant (NHMRC GNT1156519) and MS Research Australia (grants 18-0424, 19-0665). Go to Neurology.org/N for full disclosures.
Publisher Copyright:
Copyright © 2021 American Academy of Neurology
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Methods Using data from the MSBase Registry, we included pregnancies conceived after December 31, 2010, in 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. Results We included 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27-0.32), fell to 0.19 (0.14-0.24) in the 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 (odds ratio 0.76 per month [0.60-0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [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). We found that 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. Conclusion 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 reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications.
AB - Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Methods Using data from the MSBase Registry, we included pregnancies conceived after December 31, 2010, in 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. Results We included 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27-0.32), fell to 0.19 (0.14-0.24) in the 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 (odds ratio 0.76 per month [0.60-0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [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). We found that 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum. Conclusion 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 reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications.
UR - http://www.scopus.com/inward/record.url?scp=85114607131&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000012084
DO - 10.1212/WNL.0000000000012084
M3 - Article
C2 - 33879599
AN - SCOPUS:85114607131
SN - 0028-3878
VL - 96
SP - E2989-E3002
JO - Neurology
JF - Neurology
IS - 24
ER -