Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study

Sandra Vukusic (1, 2, 3) , Iuliana Ionescu (3, 2) , Catherine Cornu (4, 5) , Nadine Bossard (4, 6) , Françoise Durand-Dubief (7, 2) , François Cotton (7, 8) , Luca Durelli (9) , Romain Marignier (1, 2) , Laurence Gignoux (3, 2) , David-Axel Laplaud (10, 11) , Thibault Moreau (12) , Pierre Clavelou (13) , Jérôme de Seze (14) , Marc Debouverie (15) , David Brassat (16, 17) , Jean Pelletier (18) , Christine Lebrun-Frenay (19) , Emmanuelle Le Page (20, 21) , Giovanni Castelnovo (22) , Eric Berger (23) , Patrick Hautecoeur (24) , Olivier Heinzlef (25) , Maria Trojano (26) , Francesco Patti (27) , Etienne-Emile Baulieu (28) , Laurent Remontet (4, 6) , Martine El-Etr (28)

1 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
2 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
3 OFSEP - Observatoire Français de la Sclérose En Plaques [Lyon]
4 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
5 SHUPT Lyon - Service Hospitalo-Universitaire de Pharmacologie et Toxicologie - Lyon
6 Service de Biostatistiques [Lyon]
7 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
8 Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL]
9 UNITO - Università degli studi di Torino = University of Turin
10 CHU Nantes - Centre Hospitalier Universitaire de Nantes
11 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
12 Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon)
13 Neuro-Dol - Neuro-Dol
14 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
15 APEMAC - Maladies chroniques, santé perçue, et processus d'adaptation
16 CPTP - Centre de Physiopathologie Toulouse Purpan
17 Pôle Neurosciences [CHU Toulouse]
18 APHM - Assistance Publique - Hôpitaux de Marseille
19 URRIS UR2CA - Unité de Recherche Clinique de la Côte d’Azur
20 CIC - Centre d'Investigation Clinique [Rennes]
21 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
22 Pôle NIRR - Service de Neurologie [CHU Nimes]
23 Service de Neurologie [CHRU Besançon]
24 Département de neurologie [Lille]
25 CHI Poissy-Saint-Germain
26 UNIBA - Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro
27 Unict - Università degli studi di Catania = University of Catania
28 Petites Molécules de neuroprotection, neurorégénération et remyélinisation

BACKGROUND: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. OBJECTIVE: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. METHODS: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. RESULTS: Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) (p = 0.79)). CONCLUSION: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.

Mots clés: Multiple sclerosis; estradiol; post-partum; progesterone; relapses; sex hormones

Domaines: Sciences du Vivant [q-bio]

Sandra Vukusic, Iuliana Ionescu, Catherine Cornu, Nadine Bossard, Françoise Durand-Dubief, et al.. Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study. Multiple Sclerosis Journal, 2021, 27 (9), pp.1458-1463. ⟨10.1177/1352458520978218⟩. ⟨hal-03101890⟩