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HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome
Authors:Cristina Belizna  Francesca Pregnolato  Sebastien Abad  Jaume Alijotas-Reig  Howard Amital  Zahir Amoura  Laura Andreoli  Emmanuel Andres  Achile Aouba  Sule Apras Bilgen  Laurent Arnaud  Boris Bienvenu  Viktoria Bitsadze  Patrick Blanco  Miri Blank  Maria Orietta Borghi  Antonia Caligaro  Elisabeta Candrea  Pier Luigi Meroni
Affiliation:1. Vascular and Coagulation Department, University Hospital Angers, Angers, France;2. MITOVASC institute and CARFI facility, UMR CNRS 6015, INSERM U1083, University of Angers, Angers, France;3. Istituto Auxologico Italiano, IRCCS, Laboratory of Immunorheumatology, Milan, Italy;4. Department of Internal Medicine, Hospital Avicenne, Publique – Hôpitaux de Paris, University Paris 13, Bobigny, France;5. Systemic Autoimmune Disease Unit, Department of Internal Medicine, Vall d''Hebron University Hospital, Barcelona, Spain;6. Department of Medicine, Universitat Autonòma, Barcelona, Spain;7. The Zabludowicz Center for Autoimmune Diseases, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel;8. Internal Medicine Department 2, Pitié-Salpêtrière Hospital, French National Centre for Rare Systemic Diseases, AP-HP, Paris, France;9. Rheumatology and Clinical Immunology Unit, University of Brescia, Brescia, Italy;10. Internal Medicine Department, University Hospital Strasbourg, Strasbourg, France;11. Department of Internal Medicine, Caen University Hospital, Caen, France;12. Internal Medicine Department, Hacettepe University, Ankara, Turkey;13. Rheumatology Department, University Hospital Strasbourg, Strasbourg, France;14. Department of Internal Medicine, Saint Joseph Hospital, Marseille, France;15. Department of Obstetrics and Gynecology, I.M. Sechenow First Moscow State Medical University, Moscow, Russia;p. ImmunoConcEpT, CNRS-UMR 5164, University Bordeaux, Bordeaux, France;q. FHU ACRONIM, Bordeaux University Hospital, Place Amélie Raba Léon, 33076 Bordeaux, France;r. Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy;s. Department of Dermatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;t. Immunology, Rheumatology, Allergology and Rare Disease-IRCCS San Raffaele Hospital, Laboratory of Autoimmunity and vascular inflammation San Raffaele, Milan, Italy;u. Department of Internal Medicine and Infectious Disease, Hôpital européen Marseille, Marseille, France;v. Research Department Unit, University Hospital Angers, Angers, France;w. Nephrology Department, Maastricht University, Maastricht, the Netherlands;x. Rheumatology Department, Kaye Edmonton Clinic University of Alberta, Edmonton, Canada;y. Department of Rheumatology, County Emergency Hospital Cluj-Napoca, Cluj-Napoca, Romania;z. Rheumatology, Centre Hospitalier du Mans, 72037 Le Mans, France;11. Coagulation Laboratory, Department of Clinical Biology, Immunology and Microbiology, Ghent University Hospital, Ghent, Belgium;12. Scientific Research Department, Internal Medicine-Rheumatology Bezhanijska Kosa, University Medical Center, Belgrade University, Belgrade, Serbia;13. Department of Internal Medicine. Althaia Healthcare Network of Manresa, Barcelona, Spain;14. Departement of hematology et immunology, University Hospital Angers, Angers, France;15. Department of Internal Medicine, University Hospital Nantes, Nantes, France;16. Cytometry and Biomarkers Unit of Technology and Service, Center for Translational Science, Institut Pasteur, 28, Rue Doct Roux, 75015 Paris, France;17. Vascular Medicine Department, Grenoble University Hospital, Grenoble, France;18. Department of Internal Medicine, Archet-1 Hospital, University of Nice-Sophia-Antipolis, 151 Route de Saint Antoine de Ginestière, 06202 Nice, France;19. Department of Internal Medicine, University Hospital Rennes, Rennes, France;110. INSERM, UMR-S 1076, VRCM, Aix-Marseille University, Marseille, France;111. Centre de Néphrologie et Transplantation Rénale, AP-HM, Marseille, France;112. Publique – Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie clinique, F-94275 Le Kremlin-Bicêtre, France;113. UMR 1184, Université Paris Sud, F-94276 Le Kremlin-Bicêtre, France;114. INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicêtre, France;115. Department of Internal Medicine, University Hospital Poitiers, Poitiers, France;1p. Autoimmune and thrombophilic disorders Department, Hospital Carlos G. Durand, Buenos Aires, Argentina;1q. Department of Internal Medicine, Haut-Lévêque Hospital, 33604 Pessac, France;1r. Department of Internal Medicine, Division of Clinical Immunology, University Hospital Groningen, Groningen, the Netherlands;1s. Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, the Netherlands;1t. Department of Internal Medicine, University Hospital Jean Minjoz, Besançon, France;1u. Vascular Medicine Department, University Hospital Rennes, Rennes, France;1v. CHU Rennes, INSERM, CIC 1414, University Rennes, F-35000 Rennes, France;1w. Clinical Immunology Department, University Hospital Strasbourg, Strasbourg, France;1x. CM Unit of Epigenetic Regulation, Department of Developmental and Stem Cell Biology UMR3738 CNRS, Pasteur Institute, Paris, France;1y. Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary;1z. Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary;21. Department of Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, the Netherlands;22. InnoVTE: French Investigation Network on Venous Thromboembolique Disease, Grenoble-Alps University, France;23. Informatique, Mathématiques et Applications (IMAG) Unité Mixte de Recherche (UMR), 5525/Themas, Centre National de Recherche Scientifique (CNRS)/Techniques de l''Ingénieurie Médicale et de la Complexité (TIMC), Grenoble, France;24. Angiology Department, Clinique Anjou, Angers, France;25. Internal Medicine Sao Joao Hospital, Alameda Prof Hernani Monteiro Vila Nova de Gaia, 4200-319 Porto, Portugal;26. Vascular Medicine Department, University Hospital Nantes, Nantes, France;27. Internal Medicine Department, University Hospital La Rabta, Tunis, Tunisia;28. Department of Internal Medicine, Lariboisière Hospital, Paris Diderot University, Paris, France;29. Department of Obstetrics and Gynecology, Bordeaux University Hospital, Bordeaux, France;210. Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;211. Department of Medicine and Therapeutics, and Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China;212. Diaverum Dialysis Center, Angers, France;213. Clinical Investigation and Acces to Bioresources Department, Institut Pasteur, 28, Rue Doct Roux, 75015 Paris, France;214. Institut Arnault Tzanck, Saint-Laurent-du-Var, France;215. Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Catalonia, Spain;2p. Paris VI University, UPMC, Sorbonne Universities, Paris, France;2q. University of Normandy, Caen, France;2r. CEA, DSV/iMETI, IDMIT, F-92265 Fontenay-aux-Roses, France
Abstract:The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%–21% at 5?years in thrombotic APS and 20–28% in obstetrical APS [2, 3].Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4–16].Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency.Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial.This trial consists in two parts: a retrospective and a prospective study.The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.
Keywords:Antiphospholipid syndrome  Primary antiphospholipid syndrome  Hydroxychloroquine  Secondary prevention
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