Skip to main content

Advertisement

SpringerLink
Log in

COPP-MS: COrticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background

No specific treatment has demonstrated its effectiveness to prevent post-partum relapses for multiple sclerosis (MS) women.

Objective

To assess the effectiveness of preventive high-dose corticosteroids in the post-partum period by comparing two strategies: (1) no preventive treatment and (2) standardized preventive treatment.

Methods

We selected five French Multiple Sclerosis centers using the same post-partum strategy for their patients—either high-dose steroids (treating centers TC) or no treatment (non-treating centers NTC). We included relapsing–remitting multiple sclerosis women who delivered between January 2007 and January 2017. Our primary outcomes were the time from delivery to first relapse, EDSS progression and MRI activity between patients of treating centers and non-treating centers, after propensity-score weighting.

Results

350 patients were included (116 from treating centers, 234 from non-treating centers). For both groups, the annualized relapse rate decreased during pregnancy (0.28 in treating centers and 0.34 in non-treating centers during the third trimester) and increased during the first post-partum trimester (0.45 and 0.69, respectively) with 11% and 14% (NS) of patients facing at least one relapse, respectively. Our primary outcomes were not statistically different between both groups.

Conclusion

This study provides class III evidence that systematic high-dose corticosteroids are not associated with a reduced inflammatory activity during the post-partum period in multiple sclerosis patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T (1998) Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med 339:285–291

    Article  CAS  Google Scholar 

  2. Vukusic S, Hutchinson M, Hours M, Moreau T, Cortinovis-Tourniaire P, Adeleine P et al (2004) Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain 127(Pt 6):1353–1360

    Article  Google Scholar 

  3. Vukusic S, Ionescu I, Cornu C, Bossard N, Durand-Dubief F, Cotton F et al (2020) Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: the POPARTMUS study. Mult Scler 27:1458–1463

    Article  Google Scholar 

  4. Hughes SE, Spelman T, Gray OM, Boz C, Trojano M, Lugaresi A et al (2014) Predictors and dynamics of postpartum relapses in women with multiple sclerosis. Mult Scler 20:739–746

    Article  Google Scholar 

  5. Fragoso YD, Boggild M, Macias-Islas MA, Carra A, Schaerer KD, Aguayo A et al (2013) The effects of long-term exposure to disease-modifying drugs during pregnancy in multiple sclerosis. Clin Neurol Neurosurg 115:154–159

    Article  Google Scholar 

  6. Hellwig K, Haghikia A, Rockhoff M, Gold R (2012) Multiple sclerosis and pregnancy: experience from a nationwide database in Germany. Ther Adv Neurol Disord 5:247–253

    Article  Google Scholar 

  7. Alroughani R, Alowayesh MS, Ahmed SF, Behbehani R, Al-Hashel J (2018) Relapse occurrence in women with multiple sclerosis during pregnancy in the new treatment era. Neurology 90:e840–e846

    Article  Google Scholar 

  8. Bsteh G, Algrang L, Hegen H, Auer M, Wurth S, Di Pauli F et al (2020) Pregnancy and multiple sclerosis in the DMT era: a cohort study in Western Austria. Mult Scler 26:69–78

    Article  Google Scholar 

  9. Berenguer-Ruiz L, Gimenez-Martinez J, Palazón-Bru A, Sempere AP (2019) Relapses and obstetric outcomes in women with multiple sclerosis planning pregnancy. J Neurol 266:2512–2517

    Article  CAS  Google Scholar 

  10. Finkelsztejn A, Fragoso YD, Ferreira MLB, Lana-Peixoto MA, Alves-Leon SV, Gomes S et al (2011) The Brazilian database on pregnancy in multiple sclerosis. Clin Neurol Neurosurg 113:277–280

    Article  CAS  Google Scholar 

  11. Jesus-Ribeiro J, Correia I, Martins AI, Fonseca M, Marques I, Batista S et al (2017) Pregnancy in Multiple Sclerosis: a Portuguese cohort study. Mult Scler Relat Disord 17:63–68

    Article  Google Scholar 

  12. Langer-Gould A, Smith JB, Albers KB, Xiang AH, Wu J, Kerezsi EH et al (2020) Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort. Neurology 94:e1939–e1949

    Article  Google Scholar 

  13. Vukusic S, Durand-Dubief F, Benoit A, Marignier R, Frangoulis B, Confavreux C (2015) Natalizumab for the prevention of post-partum relapses in women with multiple sclerosis. Mult Scler 21:953–955

    Article  CAS  Google Scholar 

  14. Portaccio E, Moiola L, Martinelli V, Annovazzi P, Ghezzi A, Zaffaroni M et al (2018) Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: maternal risks. Neurology 90:e832–e839

    Article  Google Scholar 

  15. Canibaño B, Deleu D, Mesraoua B, Melikyan G, Ibrahim F, Hanssens Y (2020) Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations. J Drug Assess 9:20–36

    Article  Google Scholar 

  16. de Seze J, Chapelotte M, Delalande S, Ferriby D, Stojkovic T, Vermersch P (2004) Intravenous corticosteroids in the postpartum period for reduction of acute exacerbations in multiple sclerosis. Mult Scler J 10:596–597

    Article  Google Scholar 

  17. Avila-Ornelas J, Avila M, Stosic M, Robles L, Prieto PG, Hutton GJ et al (2011) The role of postpartum intravenous corticosteroids in the prevention of relapses in multiple sclerosis. Int J MS Care 13:91–93

    Article  Google Scholar 

  18. Hellwig K, Beste C, Schimrigk S, Chan A (2009) Immunomodulation and postpartum relapses in patients with multiple sclerosis. Ther Adv Neurol Disord 2:7–11

    Article  Google Scholar 

  19. Brandt-Wouters E, Gerlach OHH, Hupperts RMM (2016) The effect of postpartum intravenous immunoglobulins on the relapse rate among patients with multiple sclerosis. Int J Gynaecol Obstet 134:194–196

    Article  CAS  Google Scholar 

  20. Rosa GR, O’Brien AT, de Nogueira EAG, de Carvalho VM, Paz SC, Fragoso YD (2018) There is no benefit in the use of postnatal intravenous immunoglobulin for the prevention of relapses of multiple sclerosis: findings from a systematic review and meta-analysis. Arq Neuropsiquiatr 76:361–366

    Article  Google Scholar 

  21. Horvat Ledinek A, Brecl Jakob G, Jerše J, Ruška B, Pavičić T, Gabelić T et al (2020) Intravenous immunoglobulins for the prevention of postpartum relapses in multiple sclerosis. Mult Scler Relat Disord 38:101519

    Article  Google Scholar 

  22. Winkelmann A, Rommer PS, Hecker M, Zettl UK (2018) Intravenous immunoglobulin treatment in multiple sclerosis: a prospective, rater-blinded analysis of relapse rates during pregnancy and the postnatal period. CNS Neurosci Ther 25:78–85

    Article  Google Scholar 

  23. Portaccio E, Ghezzi A, Hakiki B, Sturchio A, Martinelli V, Moiola L et al (2014) Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs. J Neurol Neurosurg Psychiatry 85:845–850

    Article  Google Scholar 

  24. Vukusic S, Casey R, Rollot F, Brochet B, Pelletier J, Laplaud D-A et al (2020) Observatoire Français de la Sclérose en Plaques (OFSEP): a unique multimodal nationwide MS registry in France. Mult Scler 26:118–122

    Article  Google Scholar 

  25. Confavreux C, Compston DA, Hommes OR, McDonald WI, Thompson AJ (1992) EDMUS, a European database for multiple sclerosis. J Neurol Neurosurg Psychiatry 55:671–676

    Article  CAS  Google Scholar 

  26. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302

    Article  Google Scholar 

  27. Brookhart MA, Schneeweiss S, Rothman KJ, Glynn RJ, Avorn J, Stürmer T (2006) Variable selection for propensity score models. Am J Epidemiol 163:1149–1156

    Article  Google Scholar 

  28. Karim ME, Pellegrini F, Platt RW, Simoneau G, Rouette J, de Moor C. The use and quality of reporting of propensity score methods in multiple sclerosis literature: a review. Mult Scler. 2020;1352458520972557

  29. Simoneau G, Pellegrini F, Debray TP, Rouette J, Muñoz J, Platt RW et al (2022) Recommendations for the use of propensity score methods in multiple sclerosis research. Mult Scler. https://doi.org/10.1177/13524585221085732

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhao L, Claggett B, Tian L, Uno H, Pfeffer MA, Solomon SD et al (2016) On the restricted mean survival time curve in survival analysis. Biometrics 72:215–221

    Article  Google Scholar 

  31. RISCA: Causal Inference and Prediction in Cohort-Based Analyses version 0.9 from CRAN. https://rdrr.io/cran/RISCA/. Accessed 26 Feb 2021

  32. Voskuhl RR, Wang H, Wu TCJ, Sicotte NL, Nakamura K, Kurth F et al (2016) Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol 15:35–46

    Article  CAS  Google Scholar 

  33. Hellwig K, Rockhoff M, Herbstritt S, Borisow N, Haghikia A, Elias-Hamp B et al (2015) Exclusive breastfeeding and the effect on postpartum multiple sclerosis relapses. JAMA Neurol 72:1132–1138

    Article  Google Scholar 

  34. Krysko KM, Rutatangwa A, Graves J, Lazar A, Waubant E (2020) Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis. JAMA Neurol 77:327–338

    Article  Google Scholar 

  35. Couvrat-Desvergnes G, Foucher Y, Le Borgne F, Dion A, Mourad G, Garrigue V et al (2019) Comparison of graft and patient survival according to the transplantation centre policy for 1-year screening biopsy among stable kidney recipients: a propensity score-based study. Nephrol Dial Transplant 34:703–711

    Article  CAS  Google Scholar 

  36. Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C et al (1997) Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62:112–118

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The present study is supported by a grant from the ARSEP. This work has been done with data from the OFSEP (http://www.ofsep.org/fr/http://www.ofsep.org/fr/), which is supported by a grant provided by the French State and handled by the Agence Nationale de la Recherche within the framework of the Investments for the Future program under the reference ANR-10-COHO-002 OFSEP and by the Eugene Devic Foundation Against Multiple Sclerosis. The authors thank the technicians of participating centers for their help (Mr Leport from Rennes, Mrs Moyon from Nantes, Mrs Callier from Nice, Mrs Berthe from Strasbourg). The authors also thank Merck Serono for partly supporting this study.

Funding

This work has been granted by the Eugene Devic EDMUS Foundation against Multiple Sclerosis and by the Aide à la Recherche sur la Sclérose en Plaques (ARSEP) foundation.

Author information

Author notes

  1. Soizic Leguy and Mathilde Lefort: co-first authors.

Authors and Affiliations

  1. Neurology Department, CRC-SEP Rennes, Rennes Clinical Investigation Center, Rennes University Hospital Rennes University INSERM, CHU Pontchaillou, 35033, Rennes, France

    Soizic Leguy, Lucile Lescot, Emmanuelle Le Page, Gilles Edan, Anne Kerbrat & Laure Michel

  2. EHESP, CNRS, Inserm, Arènes, UMR 6051, RSMS (Recherche sur les Services et Management en Santé), University Rennes, U 1309, 35000, Rennes, France

    Mathilde Lefort, Audrey Michaud & Emmanuelle Leray

  3. CHU Rennes, Inserm, CIC 1414 [(Centre d’Investigation Clinique de Rennes)], University Rennes, 35000, Rennes, France

    Mathilde Lefort, Emmanuelle Le Page, Gilles Edan, Anne Kerbrat, Emmanuelle Leray & Laure Michel

  4. Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation et Centre de Recherche, Ressources et Compétences sur la Sclérose en Plaques, Hospices Civils de Lyon, 69677, Bron, France

    Sandra Vukusic

  5. Inserm 1028 et CNRS UMR 5292, Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, 69003, Lyon, France

    Sandra Vukusic

  6. Université de Lyon, université Claude-Bernard Lyon 1, 69000, Lyon, France

    Sandra Vukusic

  7. Eugène Devic EDMUS Foundation Against Multiple Sclerosis, state-approved foundation, 69677, Bron, France

    Sandra Vukusic

  8. CRCSEP, CHU de Nice Pasteur 2, Université Nice Côte d’Azur UR2CA URRIS, Nice, France

    Christine Lebrun-Frenay & Jérôme De Sèze

  9. Centre d’investigation Clinique, INSERM U1434, Centre Hospitalier Universitaire de Strasbourg, 1 Place de l’Hôpital, 67000, Strasbourg, France

    Jérôme De Sèze

  10. Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM; Université de Nantes, CHU de Nantes France, Nantes, France

    David-Axel Laplaud & Sandrine Wiertlewski

  11. Microenvironment, Cell Differentiation, Immunology and Cancer Unit, INSERM, Rennes I University, French Blood Agency, Rennes, France

    Laure Michel

Authors
  1. Soizic Leguy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mathilde Lefort
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lucile Lescot
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Audrey Michaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sandra Vukusic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emmanuelle Le Page
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gilles Edan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anne Kerbrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christine Lebrun-Frenay
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jérôme De Sèze
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. David-Axel Laplaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sandrine Wiertlewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Emmanuelle Leray
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Laure Michel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laure Michel.

Ethics declarations

Conflict of interest

LM received honoraria as speaker from Biogen, Merck Serono, BMS Celgene, Sanofi Genzyme, Roche, and Novartis. SV reports consulting and lecture fees, travel grants and research support from Biogen, Celgène, Novartis, Merck, Roche, Sanofi Genzyme and Teva Pharm. DAL has received consulting and lecturing fees, travel grants and unconditional research support from Biogen, Genzyme, Novartis, Merck, Roche, Sanofi, Medday, Teva Pharma and BMS. SW received honoraria as speaker or consultant from Alexion, Biogen, Merck Serono, Roche, and Novartis. ELP received honoraria for lectures or consulting from Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, TEVA, Roche, Alexion. SL, ML, LL, AM, GE, AK, JDS, CLF, EL have no no conflict of interest regarding this work.

Ethical approval

All procedures performed this study were in accordance with the ethical standards of the institutional and national research committee. The present study received approval from the Comité de Protection des Personnes on April 16th 2019 (registration number SI: 19.03.05.63609) and was declared to the Agence Nationale de Sécurité du Médicament et des produits de santé (ID RCB:2019-A00567-50).

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 28 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leguy, S., Lefort, M., Lescot, L. et al. COPP-MS: COrticosteroids during the Post-Partum in relapsing Multiple Sclerosis patients. J Neurol 269, 5571–5581 (2022). https://doi.org/10.1007/s00415-022-11215-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-022-11215-7

Keywords

Search

Navigation