Search

Your search keyword '"Boris Bienvenu"' showing total 221 results
Start Over Author "Boris Bienvenu"
221 results on '"Boris Bienvenu"'

1. Cellular pattern and orbital fat involvement are possible risk factors for the failure of corticosteroids in patients with pure idiopathic orbital inflammation syndrome: lessons from the French prospective SIOI cohort study (part II)

Author

David Saadoun, Eric Vicaut, Valérie Touitou, Jacques Lagier, Frédéric Mouriaux, Pierre-Yves Robert, Antoine Rousseau, Nicolas Schleinitz, Jean-Marie Michot, Loic Guillevin, Matthieu Groh, Antoine Martin, Philippe Blanche, Sébastien Abad, Robin Dhote, Felix Ackermann, Boris Bienvenu, Olivier Galatoire, Sophie Coffin-Pichonnet, Pierre Aucouturier, Françoise Heran, Bertrand Vabres, Ambre La Rosa, Stéphane Tran Ba, Nahla Cucherousset, Neila Sedira, Emmanuel Héron, Aïcha Abbas, Mboup Bassirou, Isabelle Badelon, Mathieu Zmuda, Alain Ducasse, Isabelle Larré, Amélie Brabant-Viau, Jean Luc George, Jean Maalouf, Anne-Laure Fisch, Nathalie Tieulé, Juliette Delmas, Alexandre Vallon, Natahlie Massart, Marie Alexandra Alyanakian, Pierre Olivier Schischmanoff, Nabila Pizzi, Nathalie Kingue-Elessa, Jad Abou Ghantous, and Solohaja-Faniaha Dimby

Subjects
Ophthalmology, RE1-994
Abstract

Purpose To better characterise the effects of corticosteroids on the course of pure idiopathic orbital inflammation syndrome (pIOIS).Methods This was a national, multicentre, prospective, non-interventional cohort study (SIOI). Among the 35 patients with histologically proven orbital inflammation who had previously been studied for their IgG4 immunostaining status, we selected those with a negative IgG4 status (ie, pIOIS) who received corticosteroids as single first-line treatment. Clinical, morphological and pathological findings at diagnosis and during follow-up from treatment initiation to study completion were analysed. Patients were assessed for their response to prednisone after the 24-month prospective phase in terms of remission (≤10 mg/d) or failure (>10 mg/d). Daily standard doses of prednisone (DSDP) were calculated at different time-points and compared between response groups.Results Of the 17 patients with pIOIS included in the final analysis, two-thirds received corticosteroids only. DSDP (mg/kg-day) were significantly higher at the time of failure in eight patients (47%) than in nine (53%) remitting at M24 (0.16 vs 0.045; p: 0.03). Notably, patients with pIOIS with a cellular pattern or orbital fat involvement tended to receive higher daily corticosteroid doses in the event of failure than remission (0.16 vs 0.045 and 0.12 vs 0.042, respectively). During treatment, maximal DSDP was 0.52 in failed patients.Conclusion The highest corticosteroid doses were insufficient to prevent failure in patients with pIOIS, particularly in those with a cellular pattern or orbital fat involvement. Large-scale interventional studies are now necessary to clarify prognostic factors and optimise corticosteroid management in patients with pIOIS.

Published
2024
Full Text
View/download PDF

2. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trialsResearch in context

Author

Ilias I. Siempos, Andre C. Kalil, Drifa Belhadi, Viviane Cordeiro Veiga, Alexandre Biasi Cavalcanti, Westyn Branch-Elliman, Eleni Papoutsi, Konstantinos Gkirgkiris, Nikoleta A. Xixi, Anastasia Kotanidou, Olivier Hermine, Raphaël Porcher, Xavier Mariette, Philippe Ravaud, Serge Bureau, Maxime Dougados, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Annick Tibi, Elie Azoulay, Jacques Cadranel, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Karine Lacombe, Matthieu Mahevas, Frédéric Pene, Valerie Pourchet-Martinez, Frédéric Schlemmer, Yazdan Yazdanpanah, Gabriel Baron, Elodie Perrodeau, Damien Vanhoye, Cécile Kedzia, Lauren Demerville, Anne Gysembergh-Houal, Alexandre Bourgoin, Nabil Raked, Lakhdar Mameri, Claire Montlahuc, Lucie Biard, St.phanie Alary, Samir Hamiria, Thinhinane Bariz, Hala Semri, Dhiaa Meriem Hai, Moustafa Benafla, Mohamed Belloul, Pernelle Vauboin, Saskia Flamand, Claire Pacheco, Anouk Walter-Petrich, Emilia Stan, Souad Benarab, Corine Nyanou, Robin Charreteur, Céline Dupre, Kévin Cardet, Blandine Lehmann, Kamyl Baghli, Claire Madelaine, Eric D'Ortenzio, Oriane Puéchal, Caroline Semaille, Laurent Savale, Anatole Harrois, Samy Figueiredo, Jacques Duranteau, Nadia Anguel, Arthur Pavot, Xavier Monnet, Christian Richard, Jean-Louis Teboul, Philippe Durand, Pierre Tissieres, Mitja Jevnikar, David Montani, Stephan Pavy, Gaétane Nocturne, Samuel Bitoun, Nicolas Noel, Olivier Lambotte, Lelia Escaut, Stephane Jauréguiberry, Elodie Baudry, Christiane Verny, Edouard Lefevre, Mohamad Zaidan, Domitille Molinari, Gaël Leprun, Alain Fourreau, Laurent Cylly, Lamiae Grimaldi, Myriam Virlouvet, Ramdane Meftali, Soléne Fabre, Marion Licois, Asmaa Mamoune, Yacine Boudali, Clotilde Le Tiec, Céline Verstuyft, Anne-Marie Roques, Sophie Georgin-Lavialle, Patricia Senet, Gilles Pialoux, Angele Soria, Antoine Parrot, Helene François, Nathalie Rozensztajn, Emmanuelle Blin, Pascaline Choinier, Juliette Camuset, Jean-Simon Rech, Antony Canellas, Camille Rolland-Debord, Nadege Lemarié, Nicolas Belaube, Marine Nadal, Martin Siguier, Camille Petit-Hoang, Julie Chas, Elodie Drouet, Matthieu Lemoine, Audrey Phibel, Lucie Aunay, Eliane Bertrand, Sylviane Ravato, Marie Vayssettes, Anne Adda, Celine Wilpotte, Pélagie Thibaut, Julie Fillon, Isabelle Debrix, Soraya Fellahi, Jean-Philippe Bastard, Guillaume Lefévre, Jacques-Eric Gottenberg, Yves Hansmann, Frédéric Blanc, Sophie Ohlmann-Caillard, Vincent Castelain, Emmanuel Chatelus, Eva Chatron, Olivier Collange, François Danion, Frédéric De Blay, Pierre Diemunsch, Sophie Diemunsch, Renaud Felten, Bernard Goichot, Valentin Greigert, Aurelien Guffroy, Bob Heger, Charlotte Kaeuffer, Loic Kassegne, Anne Sophie Korganow, Pierrick Le Borgne, Nicolas Lefebvre, Paul-Michel Mertes, Eric Noll, Mathieu Oberlin, Vincent Poindron, Julien Pottecher, Yvon Ruch, François Weill, Nicolas Meyer, Emmanuel Andres, Eric Demonsant, Hakim Tayebi, Gabriel Nisand, Stéphane Brin, Cédric Sublon, Guillaume Becker, Anne Hutt, Tristan Martin, Sophie Bayer, Catherine Metzger, Arsene Mekinian, Noémie Abisror, Amir Adedjouma, Diane Bollens, Marion Bonneton, Nathalie Bourcicaux, Anne Bourrier, Maria Chauchard Thibault Chiarabiani, Doroth.e Chopin, Jonathan Cohen, Ines Devred, Bruno Donadille, Olivier Fain, Geoffrey Hariri, Vincent Jachiet, Patrick Ingliz, Marc Garnier, Marc Gatfosse, Etienne Ghrenassia, Delphine Gobert, Jessica Krause le Garrec, Cecilia Landman, Jean Remy Lavillegrand, Benedicte Lefebvre, Thibault Mahevas, Sandie Mazerand, Jean Luc Meynard, Marjolaine Morgand, Zineb Ouaz.ne, Jerome Pacanowski, S.bastien Riviere, Philippe Seksik, Harry Sokol, Heithem Soliman, Nadia Valin, Thomas Urbina, Chloé McAvoy, Maria Pereira Miranda, Gladys Aratus, Laurence Berard, Tabassome Simon, Anne Daguenel Nguyen, Elise Girault, Cl.mentine Mayala-Kanda, Marie Antignac, Céline Leplay, Jean-Benoit Arlet, Jean-Luc Diehl, Florence Bellenfant, Anne Blanchard, Alexandre Buffet, Bernard Cholley, Antoine Fayol, Edouard Flamarion, Anne Godier, Thomas Gorget, Sophie-Rym Hamada, Caroline Hauw-Berlemont, Jean-Sébastien Hulot, David Lebeaux, Marine Livrozet, Adrien Michon, Arthur Neuschwander, Marie-Aude Pennet, Benjamin Planquette, Brigitte Ranque, Olivier Sanchez, Geoffroy Volle, Sandrine Briois, Mathias Cornic, Virginie Elisee, Jesuthasan Denis, Juliette Djadi-Prat, Pauline Jouany, Ramon Junquera, Mickael Henriques, Amina Kebir, Isabelle Lehir, Jeanne Meunier, Florence Patin, Val.rie Paquet, Anne Tréhan, Véronique Vigna, Brigitte Sabatier, Damien Bergerot, Charléne Jouve, Camille Knosp, Olivia Lenoir, Nassim Mahtal, Léa Resmini, Xavier Lescure, Jade Ghosn, Antoine Bachelard, Anne Rachline, Valentina Isernia, Bao-chau, Phung, Dorothée Vallois, Aurelie Sautereau, Catherine Neukrich, Antoine Dossier, Raphaël Borie, Bruno Crestani, Gregory Ducrocq, Philippe Gabriel Steg, Philippe Dieude, Thomas Papo, Estelle Marcault, Marhaba Chaudhry, Charléne Da Silveira, Annabelle Metois, Ismahan Mahenni, Meriam Meziani, Cyndie Nilusmas, Sylvie Le Gac, Awa Ndiaye, Fran.oise Louni, Malikhone Chansombat, Zelie Julia, Solaya Chalal, Lynda Chalal, Laura Kramer, Jeniffer Le Grand, Kafif Ouifiya, Valentine Piquard, Sarah Tubiana, Yann Nguyen, Vasco Honsel, Emmanuel Weiss, Anais Codorniu, Virginie Zarrouk, Victoire de Lastours, Matthieu Uzzan, Naura Gamany, Agathe Claveirole, Alexandre Navid, Tiffanie Fouque, Yonathan Cohen, Maya Lupo, Constance Gilles, Roza Rahli, Zeina Louis, David Boutboul, Lionel Galicier, Yaël Amara, Gabrielle Archer, Amira Benattia, Anne Bergeron, Louise Bondeelle, Nathalie de Castro, Melissa Clément, Michaël Darmon, Blandine Denis, Clairelyne Dupin, Elsa Feredj, Delphine Feyeux, Adrien Joseph, Etienne Lenglin, Pierre Le Guen, Geoffroy Liégeon, Gwenaël Lorillon, Asma Mabrouki, Eric Mariotte, Grégoire Martin de Frémont, Adrien Mirouse, Jean-Michel Molina, Régis Peffault de Latour, Eric Oksenhendler, Julien Saussereau, Abdellatif Tazi, Jean-Jacques Tudesq, Lara Zafrani, Isabelle Brindele, Emmanuelle Bugnet, Karine Celli Lebras, Julien Chabert, Lamia Djaghout, Catherine Fauvaux, Anne Lise Jegu, Ewa Kozakiewicz, Martine Meunier, Marie-Thérèse Tremorin, Claire Davoine, Isabelle Madelaine, Sophie Caillat-Zucman, Constance Delaugerre, Florence Morin, Damien Sène, Ruxandra Burlacu, Benjamin Chousterman, Bruno Mégarbanne, Pascal Richette, Jean-Pierre Riveline, Aline Frazier, Eric Vicaut, Laure Berton, Tassadit Hadjam, Miguel Alejandro Vazquez-Ibarra, Clément Jourdaine, Olivia Tran, Véronique Jouis, Aude Jacob, Julie Smati, Stéphane Renaud, Claire Pernin, Lydia Suarez, Luca Semerano, Sébastien Abad, Ruben B. nainous, Nicolas Bonnet, Celine Comparon, Yves Cohen, Hugues Cordel, Robin Dhote, Nathalie Dournon, Boris Duchemann, Nathan Ebstein, Thomas Gille, Benedicte Giroux-Leprieur, Jeanne Goupil de Bouille, Hilario Nunes, Johanna Oziel, Dominique Roulot, Lucile Sese, ClaireTantet, Yurdagul Uzunhan, Coralie Bloch-Queyrat, Vincent Levy, Fadhila Messani, Mohammed Rahaoui, Myléne Petit, Sabrina Brahmi, Vanessa Rathoin, Marthe Rigal, Nathalie Costedoat-Chalumeau, Liem Binh Luong, Zakaria Ait Hamou, Sarah Benghanem, Philippe Blanche, Nicolas Carlier, Benjamin Chaigne, Remy Gauzit, Hassan Joumaa, Mathieu Jozwiak, Marie Lachétre, Hélène Lafoeste, Odie Launay, Paul Legendre, Jonathan Marey, Caroline Morbieu, Lola-Jade Palmieri, Tali-Anne Szwebel, Hendy Abdoul, Alexandra Bruneau, Audrey Beclin-Clabaux, Charly Larrieu, Pierre Montanari, Eric Dufour, Ada Clarke, Catherine Le Bourlout, Nathalie Marin, Nathalie Menage, Samira Saleh-Mghir, Mamadou Salif Cisse, Kahina Cheref, Corinne Guerin, Jérémie Zerbit, Marc Michel, Sébastien Gallien, Etienne Crickx, Benjamin Le Vavasseur, Emmanuelle Kempf, Karim Jaffal, William Vindrios, Julie Oniszczuk, Constance Guillaud, Pascal Lim, Elena Fois, Giovanna Melica, Marie Matignon, Maud Jalabert, Jean-Daniel Lelièvre, David Schmitz, Marion Bourhis, Sylia Belazouz, Laetitia Languille, Caroline Boucle, Nelly Cita, Agnés Didier, Fahem Froura, Katia Ledudal, Thiziri Sadaoui, Alaki Thiemele, Delphine Le Febvre De Bailly, Muriel Carvhalo Verlinde, Julien Mayaux, Patrice Cacoub, David Saadoun, Mathieu Vautier, Héléne Bugaut, Olivier Benveniste, Yves Allenbach, Gaëlle Leroux, Aude Rigolet, Perrine Guillaume-Jugnot, Fanny Domont, Anne Claire Desbois, Chloé Comarmond, Nicolas Champtiaux, Segolene Toquet, Amine Ghembaza, Matheus Vieira, Georgina Maalouf, Goncalo Boleto, Yasmina Ferfar, Jean-Christophe Corvol, C.line Louapre, Sara Sambin, Louise-Laure Mariani, Carine Karachi, Florence Tubach, Candice Estellat, Linda Gimeno, Karine Martin, Aicha Bah, Vixra Keo, Sabrine Ouamri, Yasmine Messaoudi, Nessima Yelles, Pierre Faye, Sebastien Cavelot, Cecile Larcheveque, Laurence Annonay, Jaouad Benhida, Aida Zahrate-Ghoul, Soumeya Hammal, Ridha Belilita, Fanny Charbonnier, Claire Aguilar, Fanny Alby-Laurent, Carole Burger, Clara Campos-Vega, Nathalie Chavarot, Benjamin Fournier, Claire Rouzaud, Damien Vimpére, Caroline Elie, Prissile Bakouboula, Laure Choupeaux, Sophie Granville, Elodie Issorat, Christine Broissand, Marie-Alexandra Alyanakian, Guillaume Geri, Nawal Derridj, Naima Sguiouar, Hakim Meddah, Mourad Djadel, Héléne Chambrin-Lauvray, Jean-Charles Duclos-vallée, Faouzi Saliba, Sophie-Caroline Sacleux, Ilias Kounis, Sonia Tamazirt, Eric Rudant, Jean-Marie Michot, Annabelle Stoclin, Emeline Colomba, Fanny Pommeret, Christophe Willekens, Rosa Da Silva, Valérie Dejean, Yasmina Mekid, Ines Ben-Mabrouk, Florence Netzer, Caroline Pradon, Laurence Drouard, Valérie Camara-Clayette, Alexandre Morel, Gilles Garcia, Abolfazl Mohebbi, Férial Berbour, Mélanie Dehais, Anne-Lise Pouliquen, Alison Klasen, Loren Soyez-Herkert, Jonathan London, Younes Keroumi, Emmanuelle Guillot, Guillaume Grailles, Younes El amine, Fanny Defrancq, Hanane Fodil, Chaouki Bouras, Dominique Dautel, Nicolas Gambier, Thierno Dieye, Boris Bienvenu, Victor Lancon, Laurence Lecomte, Kristina Beziriganyan, Belkacem Asselate, Laure Allanic, Elena Kiouris, Marie-Héléne Legros, Christine Lemagner, Pascal Martel, Vincent Provitolo, Félix Ackermann, Mathilde Le Marchand, Aurélie Chan Hew Wai, Dimitri Fremont, Elisabeth Coupez, Mireille Adda, Frédéric Duée, Lise Bernard, Antoine Gros, Estelle Henry, Claire Courtin, Anne Pattyn, Pierre-Grégoire Guinot, Marc Bardou, Agnes Maurer, Julie Jambon, Amélie Cransac, Corinne Pernot, Bruno Mourvillier, Eric Marquis, Philippe Benoit, Damien Roux, Coralie Gernez, Cécile Yelnik, Julien Poissy, Mandy Nizard, Fanette Denies, Helene Gros, Jean-Jacques Mourad, Emmanuelle Sacco, Sophie Renet, F. Ader, Y. Yazdanpanah, F. Mentre, N. Peiffer-Smadja, F.X. Lescure, J. Poissy, L. Bouadma, J.F. Timsit, B. Lina, F. Morfin-Sherpa, M. Bouscambert, A. Gaymard, G. Peytavin, L. Abel, J. Guedj, C. Andrejak, C. Burdet, C. Laouenan, D. Belhadi, A. Dupont, T. Alfaiate, B. Basli, A. Chair, S. Laribi, J. Level, M. Schneider, M.C. Tellier, A. Dechanet, D. Costagliola, B. Terrier, M. Ohana, S. Couffin-Cadiergues, H. Esperou, C. Delmas, J. Saillard, C. Fougerou, L. Moinot, L. Wittkop, C. Cagnot, S. Le Mestre, D. Lebrasseur-Longuet, V. Petrov-Sanchez, A. Diallo, N. Mercier, V. Icard, B. Leveau, S. Tubiana, B. Hamze, A. Gelley, M. Noret, E. D’Ortenzio, O. Puechal, C. Semaille, T. Welte, J.A. Paiva, M. Halanova, M.P. Kieny, E. Balssa, C. Birkle, S. Gibowski, E. Landry, A. Le Goff, L. Moachon, C. Moins, L. Wadouachi, C. Paul, A. Levier, D. Bougon, F. Djossou, L. Epelboin, J. Dellamonica, C.H. Marquette, C. Robert, S. Gibot, E. Senneville, V. Jean-Michel, Y. Zerbib, C. Chirouze, A. Boyer, C. Cazanave, D. Gruson, D. Malvy, P. Andreu, J.P. Quenot, N. Terzi, K. Faure, C. Chabartier, V. Le Moing, K. Klouche, T. Ferry, F, Valour, B. Gaborit, E. Canet, P. Le Turnier, D. Boutoille, F. Bani-Sadr, F. Benezit, M. Revest, C. Cameli, A. Caro, MJ Ngo Um Tegue, Y. Le Tulzo, B. Laviolle, F. Laine, G. Thiery, F. Meziani, Y. Hansmann, W. Oulehri, C. Tacquard, F. Vardon-Bounes, B. Riu-Poulenc, M. Murris-Espin, L. Bernard, D. Garot, O. Hinschberger, M. Martinot, C. Bruel, B. Pilmis, O. Bouchaud, P. Loubet, C. Roger, X. Monnet, S. Figueiredo, V. Godard, J.P. Mira, M. Lachatre, S. Kerneis, J. Aboab, N. Sayre, F. Crockett, D. Lebeaux, A. Buffet, J.L. Diehl, A. Fayol, J.S. Hulot, M. Livrozet, A Mekontso- Dessap, C. Ficko, F. Stefan, J. Le Pavec, J. Mayaux, H. Ait-Oufella, J.M. Molina, G. Pialoux, M. Fartoukh, J. Textoris, M. Brossard, A. Essat, E. Netzer, Y. Riault, M. Ghislain, L. Beniguel, M. Genin, L. Gouichiche, C. Betard, L. Belkhir, A. Altdorfer, V Fraipont Centro, S. Braz, JM Ferreira Ribeiro, R Roncon Alburqueque, M. Berna, M. Alexandre, B. Lamprecht, A. Egle, R. Greil, M. Joannidis, Thomas F. Patterson, Philip O. Ponce, Barbara S. Taylor, Jan E. Patterson, Jason E. Bowling, Heta Javeri, LuAnn Larson, Angela Hewlett, Aneesh K. Mehta, Nadine G. Rouphael, Youssef Saklawi, Nicholas Scanlon, Jessica J. Traenkner, Ronald P. Trible, Jr., Emmanuel B. Walter, Noel Ivey, Thomas L. Holland, Guillermo M. Ruiz-Palacios, Alfredo Ponce de León, Sandra Rajme, Lanny Hsieh, Alpesh N. Amin, Miki Watanabe, Helen S. Lee, Susan Kline, Joanne Billings, Brooke Noren, Hyun Kim, Tyler D. Bold, Victor Tapson, Jonathan Grein, Fayyaz Sutterwala, Nicole Iovine, Lars K. Beattie, Rebecca Murray Wakeman, Matthew Shaw, Mamta K. Jain, Satish Mocherla, Jessica Meisner, Amneris Luque, Daniel A. Sweeney, Constance A. Benson, Farhana Ali, Robert L. Atmar, Hana M. El Sahly, Jennifer Whitaker, Ann R. Falsey, Angela R. Branche, Cheryl Rozario, Justino Regalado Pineda, José Arturo Martinez-Orozco, David Chien Lye, Sean WX. Ong, Po Ying Chia, Barnaby E. Young, Uriel Sandkovsky, Mezgebe Berhe, Clinton Haley, Emma Dishner, Valeria D. Cantos, Colleen F. Kelley, Paulina A. Rebolledo Esteinou, Sheetal Kandiah, Sarah B. Doernberg, Pierre-Cedric B. Crouch, Hannah Jang, Anne F. Luetkemeyer, Jay Dwyer, Stuart H. Cohen, George R. Thompson, 3rd, Hien H. Nguyen, Robert W. Finberg, Jennifer P. Wang, Juan Perez-Velazquez, Mireya Wessolossky, Patrick E.H. Jackson, Taison D. Bell, Miranda J. West, Babafemi Taiwo, Karen Krueger, Johnny Perez, Triniece Pearson, Catharine I. Paules, Kathleen G. Julian, Danish Ahmad, Alexander G. Hajduczok, Henry Arguinchona, Christa Arguinchona, Nathaniel Erdmann, Paul Goepfert, Neera Ahuja, Maria G. Frank, David Wyles, Heather Young, Myoung-don Oh, Wan Beom Park, Chang Kyung Kang, Vincent Marconi, Abeer Moanna, Sushma Cribbs, Telisha Harrison, Eu Suk Kim, Jongtak Jung, Kyoung-Ho Song, Hong Bin Kim, Seow Yen Tan, Humaira Shafi, MF Jaime Chien, Raymond KC. Fong, Daniel D. Murray, Jens Lundgren, Henrik Nielsen, Tomas Jensen, Barry S. Zingman, Robert Grossberg, Paul F. Riska, Otto O. Yang, Jenny Ahn, Rubi Arias, Rekha R. Rapaka, Naomi Hauser, James D. Campbell, William R. Short, Pablo Tebas, Jillian T. Baron, Susan L.F. McLellan, Lucas S. Blanton, Justin B. Seashore, C. Buddy Creech, Todd W. Rice, Shannon Walker, Isaac P. Thomsen, Diego Lopez de Castilla, Jason W. Van Winkle, Francis X. Riedo, Surinder Kaur Pada, Alvin DY. Wang, Li Lin, Michelle Harkins, Gregory Mertz, Nestor Sosa, Louis Yi Ann Chai, Paul Anantharajah Tambyah, Sai Meng Tham, Sophia Archuleta, Gabriel Yan, David A. Lindholm, Ana Elizabeth Markelz, Katrin Mende, Richard Mularski, Elizabeth Hohmann, Mariam Torres-Soto, Nikolaus Jilg, Ryan C. Maves, Gregory C. Utz, Sarah L. George, Daniel F. Hoft, James D. Brien, Roger Paredes, Lourdes Mateu, Cora Loste, Princy Kumar, Sarah Thornton, Sharmila Mohanraj, Noreen A. Hynes, Lauren M. Sauer, Christopher J. Colombo, Christina Schofield, Rhonda E. Colombo, Susan E. Chambers, Richard M. Novak, Andrea Wendrow, Samir K. Gupta, Tida Lee, Tahaniyat Lalani, Mark Holodniy, Aarthi Chary, Nikhil Huprikar, Anuradha Ganesan, Norio Ohmagari, Ayako Mikami, D. Ashley Price, Christopher J.A. Duncan, Kerry Dierberg, Henry J. Neumann, Stephanie N. Taylor, Alisha Lacour, Najy Masri, Edwin Swiatlo, Kyle Widmer, James D. Neaton, Mary Bessesen, David S. Stephens, Timothy H. Burgess, Timothy M. Uyeki, Robert Walker, G. Lynn Marks, Anu Osinusi, Huyen Cao, Anabela Cardoso, Stephanie de Bono, Douglas E. Schlichting, Kevin K. Chung, Jennifer L. Ferreira, Michelle Green, Mat Makowski, Michael R. Wierzbicki, Tom M. Conrad, Jill Ann El-Khorazaty, Heather Hill, Tyler Bonnett, Nikki Gettinger, Theresa Engel, Teri Lewis, Jing Wang, John H. Beigel, Kay M. Tomashek, Varduhi Ghazaryan, Tatiana Beresnev, Seema Nayak, Lori E. Dodd, Walla Dempsey, Effie Nomicos, Marina Lee, Rhonda Pikaart-Tautges, Mohamed Elsafy, Robert Jurao, Hyung Koo, Michael Proschan, Tammy Yokum, Janice Arega, Ruth Florese, Jocelyn D. Voell, Richard Davey, Ruth C. Serrano, Zanthia Wiley, Varun K. Phadke, Paul A. Goepfert, Carlos A. Gomez, Theresa A. Sofarelli, Laura Certain, Hannah N. Imlay, Cameron R. Wolfe, Emily R. Ko, John J. Engemann, Nora Bautista Felix, Claire R. Wan, Sammy T. Elmor, Laurel R. Bristow, Michelle S. Harkins, Nicole M. Iovine, Marie-Carmelle Elie-Turenne, Victor F. Tapson, Pyoeng Gyun Choe, Richard A. Mularski, Kevin S. Rhie, Rezhan H. Hussein, Dilek Ince, Patricia L. Winokur, Jin Takasaki, Sho Saito, Kimberly McConnell, PharmD, David L. Wyles, Ellen Sarcone, Kevin A. Grimes, Katherine Perez, Charles Janak, Jennifer A. Whitaker, Paulina A. Rebolledo, John Gharbin, Allison A. Lambert, Diego F. Zea, Emma Bainbridge, David C. Hostler, Jordanna M. Hostler, Brian T. Shahan, Evelyn Ling, Minjoung Go, Fleesie A. Hubbard, Melony Chakrabarty, Maryrose Laguio-Vila, Edward E. Walsh, Faheem Guirgis, Vincent C. Marconi, Christian Madar, Scott A. Borgetti, Corri Levine, Joy Nock, Keith Candiotti, Julia Rozman, Fernando Dangond, Yann Hyvert, Andrea Seitzinger, Kaitlyn Cross, Stephanie Pettibone, Seema U. Nayak, and Gregory A. Deye

Subjects
Acute respiratory distress syndrome, Acute hypoxemic respiratory failure, Pneumonia, Critically ill, Cancer, Medicine (General), R5-920
Abstract

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Published
2024
Full Text
View/download PDF

3. Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases)

Author

Patrice Cacoub, Arsène Mekinian, Zahir Amoura, Eric Hachulla, Yves Allenbach, Renaud Felten, Anne-Sophie Korganow, Christelle Sordet, Aurélien Guffroy, Xavier Mariette, Christophe Richez, Jacques-Eric Gottenberg, Alain Meyer, Jean Sibilia, Benjamin Terrier, Emmanuel Chatelus, Laurence Bouillet, Marie-Elise Truchetet, Isabelle Melki, Divi Cornec, Martin Michaud, Raphaele Seror, Bénédicte Rouvière, Pierre Quartier, Sebastien Ottaviani, Julien Henry, Valérie Devauchelle-Pensec, Claire Larroche, Azeddine Dellal, Marie Desmurs, Mathieu Jouvray, Hubert Nielly, Antoine Poulet, Guillaume Vial, Roland Jaussaud, Boris Bienvenu, Pierre-Yves Jeandel, Jean-François Kleinmann, Emeline Gaigneux, Aurélie Saunier, Amelie Leurs, Aurore Chaudier, Marc Gatfosse, Vincent Andre, Gildas Baulier, Mathieu Ete, and Samira Litim-Ahmed-Yahia

Subjects
Medicine
Abstract

Objectives To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases.Methods The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019.Results Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued.Conclusion These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Published
2022
Full Text
View/download PDF

4. Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial

Author

Cécile Janssen, Marine Cachanado, Laetitia Ninove, Marie Lachatre, Jocelyn Michon, Olivier Epaulard, Zoha Maakaroun-Vermesse, Christian Chidiac, Bruno Laviolle, Hugues Aumaitre, Ady Assaf, Karine Lacombe, Catherine Schmidt-Mutter, Elisabeth Botelho-Nevers, Magali Briere, Thomas Boisson, Paul Loubet, Boris Bienvenu, Olivier Bouchaud, Amel Touati, Christine Pereira, Alexandra Rousseau, Laurence Berard, Melissa Montil, Xavier de Lamballerie, Tabassome Simon, and Odile Launay

Subjects
Medicine (General), R5-920
Abstract

Summary: Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p

Published
2022
Full Text
View/download PDF

5. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

Author

Olivier Hermine, Xavier Mariette, Raphael Porcher, Felix Djossou, Yann Nguyen, Jean-Benoît Arlet, Laurent Savale, Jean Luc Diehl, Sophie Georgin-Lavialle, Jacques Cadranel, Gilles Pialoux, Karine Lacombe, Arsène Mekinian, Hélène Gros, Xavier Lescure, Jade Ghosn, Elisabeth Coupez, Kevin Grapin, Christophe Rapp, Marc Michel, Anne Lise Lecapitaine, Jean Marie Michot, Nathalie Costedoat-Chalumeau, Liem Binh Luong Nguyen, Luca Semerano, François Raffi, Claire Aguillar, Claire Rouzaud, Jacques Eric Gottenberg, Yves Hansmann, Boris Bienvenu, Jonathan London, Franklin Samou Fantchou, Felix Ackermann, Antoine Gros, Alexandre Morel, Nicolas Gambier, Damien Sène, Bruno Mégarbane, Elie Azoulay, Serge Bureau, Maxime Dougados, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Mathieu Mahevas, Frédéric Pène, Frédéric Schlemmer, Valérie Pourcher-Martinez, Annick Tibi, Gabriel Baron, Elodie Perrodeau, Stéphanie Baron, Gabriel Steg, Yazdan Yazdapanah, Tabassome Simon, Matthieu Resche-Rigon, Pierre-Louis Tharaux, and Philippe Ravaud

Subjects
COVID-19, Tocilizumab+Dexamethasone, Randomized clinical trial, Medicine (General), R5-920
Abstract

Summary: Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42–1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19–20–0151, PHRC COVID-19–20–0029], Fondation de l'Assistance Publique – Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale” (FRM). Tocilizumab was provided by Roche.

Published
2022
Full Text
View/download PDF

6. Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial

Author

Alexandra Audemard-Verger, Amélie Le Gouge, Vincent Pestre, Johan Courjon, Vincent Langlois, Marc-Olivier Vareil, Mathilde Devaux, Boris Bienvenu, Vincent Leroy, Radjiv Goulabchand, Léa Colombain, Adrien Bigot, Thomas Guimard, Youcef Douadi, Geoffrey Urbanski, Jean François Faucher, Laurence Maulin, Bertrand Lioger, Jean-Philippe Talarmin, Matthieu Groh, Joseph Emmerich, Sophie Deriaz, Nicole Ferreira-Maldent, Ann-Rose Cook, Céline Lengellé, Hélène Bourgoin, Arsène Mekinian, Achille Aouba, François Maillot, and Agnès Caille

Subjects
Medicine, Science
Abstract

Objective We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. Methods In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Results Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference—21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). Conclusion This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Published
2022

7. Thoracic involvement and imaging patterns in IgG4-related disease

Author

Romain Muller, Paul Habert, Mikael Ebbo, Julie Graveleau, Mathieu Groh, David Launay, Sylvain Audia, Gregory Pugnet, Fleur Cohen, Antoinette Perlat, Audrey Benyamine, Boris Bienvenu, Lea Gaigne, Pascal Chanez, Jean Yves Gaubert, and Nicolas Schleinitz

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Objective Immunoglobulin G4-related disease (IgG4-RD) is a rare orphan disease. Lung, pleura, pericardium, mediastinum, aorta and lymph node involvement has been reported with variable frequency and mostly in Asian studies. The objective of this study was to describe thoracic involvement assessed by high-resolution thoracic computed tomography (CT) in Caucasian patients with IgG4-RD. Methods Thoracic CT scans before treatment were retrospectively collected through the French case registry of IgG4-RD and a single tertiary referral centre. CT scans were reviewed by two experts in thoracic imagery blinded from clinical data. Results 48 IgG4-RD patients with thoracic involvement were analysed. All had American College of Rheumatology/European League Against Rheumatism classification scores ≥20 and comprehensive diagnostic criteria for IgG4-RD. CT scan findings showed heterogeneous lesions. Seven patterns were observed: peribronchovascular involvement (56%), lymph node enlargement (31%), nodular disease (25%), interstitial disease (25%), ground-glass opacities (10%), pleural disease (8%) and retromediastinal fibrosis (4%). In 37% of cases two or more patterns were associated. Asthma was significantly associated with peribronchovascular involvement (p=0.04). Among eight patients evaluated by CT scan before and after treatments, only two patients with interstitial disease displayed no improvement. Conclusion Thoracic involvement of IgG4-RD is heterogeneous and likely underestimated. The main thoracic CT scan patterns are peribronchovascular thickening and thoracic lymph nodes.

Published
2021
Full Text
View/download PDF

8. Early predictors of one-year mortality in patients over 65 presenting with ANCA-associated renal vasculitis: a retrospective, multicentre study

Author

Dimitri Titeca-Beauport, Alexis Francois, Thierry Lobbedez, Dominique Guerrot, David Launay, Laurence Vrigneaud, Maité Daroux, Celine Lebas, Boris Bienvenu, Eric Hachulla, Momar Diouf, and Gabriel Choukroun

Subjects
ANCA, Elderly, Glomerulonephritis, Infection, Mortality, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background The risk of early death is particularly high in patients over the age of 65 presenting with antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis. We hypothesized that by combining disease severity markers, a comorbidity index and serious adverse event reports, we would be able to identify early predictors of one-year mortality in this population. Methods We performed a multicentre, retrospective study in the nephrology and internal medicine departments of six tertiary hospitals in northern France. A total of 149 patients (median [interquartile range (IQR)] age: 72.7 [68.5–76.8] years) presenting with ANCA-associated vasculitis and renal involvement were included between January 2002 and June 2015. The primary endpoint was the one-year mortality rate. Results Renal function was severely impaired at presentation (median [IQR] peak serum creatinine (SCr): 337 [211–522] μmol/l), and 45 patients required dialysis. The Five-Factor Score (FFS, scored as + 1 point for each poor prognostic factor (age > 65 years, cardiac symptoms, gastrointestinal involvement, SCr ≥150 μmol/L, and the absence of ear, nose, and throat involvement)) was ≥3 in 120 cases. The one-year mortality rate was 19.5%. Most of the deaths occurred before month 6, and most of these were related to severe infections. In a univariate analysis, age, a high comorbidity index, a performance status of 3 or 4, a lack of co-trimoxazole prophylaxis, early severe infection, and disease activity parameters (such as the albumin level, haemoglobin level, peak SCr level, dialysis status, and high FFS) were significantly associated with one-year mortality. In a multivariable analysis, the best predictors were a high FFS (relative risk (RR) [95% confidence interval (CI)] = 2.57 [1.30–5.09]; p = 0.006) and the occurrence of a severe infection during the first month (RR [95%CI] = 2.74 [1.27–5.92]; p = 0.01). Conclusions When considering various disease severity markers in over-65 patients with ANCA-associated renal vasculitis, we found that an early, severe infection (which occurred in about a quarter of the patients) is a strong predictor of one-year mortality. A reduction in immunosuppression, the early detection of infections, and co-trimoxazole prophylaxis might help to reduce mortality in this population.

Published
2018
Full Text
View/download PDF

9. Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis

Author

Maxime Samson, Hélène Greigert, Marion Ciudad, Claire Gerard, Thibault Ghesquière, Malika Trad, Marc Corbera‐Bellalta, Coraline Genet, Sethi Ouandji, Claudie Cladière, Marine Thebault, Kim Heang Ly, Eric Liozon, François Maurier, Boris Bienvenu, Benjamin Terrier, Loïc Guillevin, Pierre Charles, Valérie Quipourt, Hervé Devilliers, Pierre‐Henry Gabrielle, Catherine Creuzot‐Garcher, Georges Tarris, Laurent Martin, Philippe Saas, Sylvain Audia, Maria Cinta Cid, and Bernard Bonnotte

Subjects
giant cell arteritis, interleukin‐6, tocilizumab, Treg, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab. Methods Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab (n = 20) or glucocorticoids (n = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T‐cell (Teff) proliferation and polarisation into Th1 and Th17 cells. Results Treg (CD4+CD25highFoxP3+) frequency in total CD4+ T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P

Published
2021
Full Text
View/download PDF

10. Evaluating the cost-consequence of a standardized strategy for the etiological diagnosis of uveitis (ULISSE study).

Author

Audrey de Parisot, Yvan Jamilloux, Laurent Kodjikian, Marie-Hélène Errera, Neila Sedira, Emmanuel Heron, Laurent Pérard, Pierre-Loïc Cornut, Christelle Schneider, Sophie Rivière, Priscille Ollé, Grégory Pugnet, Pascal Cathébras, Pierre Manoli, Bahram Bodaghi, David Saadoun, Stéphanie Baillif, Nathalie Tieulie, Marc André, Frédéric Chiambaretta, Nicolas Bonin, Philip Bielefeld, Alain Bron, Frédéric Mouriaux, Boris Bienvenu, Nassira Amamra, Pascale Guerre, Evelyne Decullier, Pascal Sève, and ULISSE group

Subjects
Medicine, Science
Abstract

MAIN OBJECTIVE:To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis. DESIGN:This was a prospective, non-inferiority, multicentre, randomized controlled trial. METHODS:We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy. RESULTS:903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p

Published
2020
Full Text
View/download PDF

11. Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study

Author

Kim-Heang Ly, Nathalie Costedoat-Chalumeau, Eric Liozon, Stéphanie Dumonteil, Jean-Pierre Ducroix, Laurent Sailler, Olivier Lidove, Boris Bienvenu, Olivier Decaux, Pierre-Yves Hatron, Amar Smail, Léonardo Astudillo, Nathalie Morel, Jonathan Boutemy, Antoinette Perlat, Eric Denes, Marc Lambert, Thomas Papo, Anne Cypierre, Elisabeth Vidal, Pierre-Marie Preux, Jacques Monteil, and Anne-Laure Fauchais

Subjects
PET/CT, chest-abdomen-pelvis CT, FUO, IUO, EFUO, Medicine
Abstract

Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p < 0.001) and DC (19.4% vs. 5.8%, p < 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months, p = 0.02). Arthralgia (OR 4.90, p = 0.0012), DO of PET/CT (OR 4.09, p = 0.016), CRP > 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis.

Published
2022
Full Text
View/download PDF

12. Superior efficacy and similar safety of double dose anakinra in Erdheim-Chester disease after single dose treatment

Author

Fréderic Franconieri, Samuel Deshayes, Hubert de Boysson, Salim Trad, Nicolas Martin Silva, Benjamin Terrier, Boris Bienvenu, Françoise Galateau-Sallé, Jean-François Emile, Alison C. Johnson, and Achille Aouba

Subjects
erdheim-chester disease, anakinra, braf mutation, nras mutation, vemurafenib, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objectives. In Erdheim-Chester disease (ECD), the empirical single dose (SD, 100 mg/day) anakinra sometimes induces only partial responses. Since SD is usually well tolerated, doubling the dose might improve response while maintaining an acceptable safety profile. Methods. A retrospective analysis was performed of outcomes under double-dose (DD) of anakinra in 4 ECD patients who did not exhibit a complete response (CR) under SD treatment. Bone, retroperitoneal, neurologic/orbital, peritoneal, pericardial, right atrium, and pleural involvements were recorded. CR, partial response (PR), stable disease, progressive disease (PD) and tolerance of DD were assessed. Results. SD treatment was a second or third line treatment in three patients after interferon-therapy failure. Two patients, including one with a BRAF mutation, achieved a CR and one patient with a NRAS mutation achieved a PR with DD treatment. The fourth patient, wild-type for both genes, did not respond to a first DD treatment, but then achieved CR under SD associated with a reduced dose of vemurafenib (960 mg/d). Bone and retroperitoneal lesions partially improved on imaging with SD in all patients, but were further improved under DD with two patients achieving CR. With SD treatment, two patients with right atrial masses showed sustained CR. Under DD treatment, two patients with massive serositis refractory to SD, showed PR. Conclusion. DD improved the response to anakinra and lead to two CRs and a PR in three out of four ECD patients, with minor and comparable side-effects to those of SD, while failures were essentially related to massive serositis.

Published
2018
Full Text
View/download PDF

13. Ehlers-Danlos Syndrome, Hypermobility Type: Impact of Somatosensory Orthoses on Postural Control (A Pilot Study)

Author

Emma G. Dupuy, Pascale Leconte, Elodie Vlamynck, Audrey Sultan, Christophe Chesneau, Pierre Denise, Stéphane Besnard, Boris Bienvenu, and Leslie M. Decker

Subjects
subjective vertical, proprioception, compressive garments, proprioceptive insoles, postural sway, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Elhers-Danlos syndrome (EDS) is the clinical manifestation of connective tissue disorders, and comprises several clinical forms with no specific symptoms and selective medical examinations which result in a delay in diagnosis of about 10 years. The EDS hypermobility type (hEDS) is characterized by generalized joint hypermobility, variable skin hyperextensibility and impaired proprioception. Since somatosensory processing and multisensory integration are crucial for both perception and action, we put forth the hypothesis that somatosensory deficits in hEDS patients may lead, among other clinical symptoms, to misperception of verticality and postural instability. Therefore, the purpose of this study was twofold: (i) to assess the impact of somatosensory deficit on subjective visual vertical (SVV) and postural stability; and (ii) to quantify the effect of wearing somatosensory orthoses (i.e., compressive garments and insoles) on postural stability. Six hEDS patients and six age- and gender-matched controls underwent a SVV (sitting, standing, lying on the right side) evaluation and a postural control evaluation on a force platform (Synapsys), with or without visual information (eyes open (EO)/eyes closed (EC)). These two latter conditions performed either without orthoses, or with compression garments (CG), or insoles, or both. Results showed that patients did not exhibit a substantial perceived tilt of the visual vertical in the direction of the body tilt (Aubert effect) as did the control subjects. Interestingly, such differential effects were only apparent when the rod was initially positioned to the left of the vertical axis (opposite the longitudinal body axis). In addition, patients showed greater postural instability (sway area) than the controls. The removal of vision exacerbated this instability, especially in the mediolateral (ML) direction. The wearing of orthoses improved postural stability, especially in the eyes-closed condition, with a particularly marked effect in the anteroposterior (AP) direction. Hence, this study suggests that hEDS is associated with changes in the relative contributions of somatosensory and vestibular inputs to verticality perception. Moreover, postural control impairment was offset, at least partially, by wearing somatosensory orthoses.

Published
2017
Full Text
View/download PDF

14. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

Author

Alexandra Audemard-Verger, Nicolas Martin Silva, Céline Verstuyft, Nathalie Costedoat-Chalumeau, Aurélie Hummel, Véronique Le Guern, Karim Sacré, Olivier Meyer, Eric Daugas, Cécile Goujard, Audrey Sultan, Thierry Lobbedez, Lionel Galicier, Jacques Pourrat, Claire Le Hello, Michel Godin, Rémy Morello, Marc Lambert, Eric Hachulla, Philippe Vanhille, Guillaume Queffeulou, Jacky Potier, Jean-Jacques Dion, Pierre Bataille, Dominique Chauveau, Guillaume Moulis, Dominique Farge-Bancel, Pierre Duhaut, Bernadette Saint-Marcoux, Alban Deroux, Jennifer Manuzak, Camille Francès, Olivier Aumaitre, Holy Bezanahary, Laurent Becquemont, and Boris Bienvenu

Subjects
Medicine, Science
Abstract

OBJECTIVE:To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS:We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS:Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION:This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Published
2016
Full Text
View/download PDF

15. Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study

Author

Grégoire Martin de Frémont, Nathalie Costedoat-Chalumeau, Estibaliz Lazaro, Rakiba Belkhir, Gaëlle Guettrot-Imbert, Nathalie Morel, Gaétane Nocturne, Anna Molto, Tiphaine Goulenok, Elisabeth Diot, Laurent Perard, Nicole Ferreira-Maldent, Maelle Le Besnerais, Nicolas Limal, Nihal Martis, Noémie Abisror, Odile Debouverie, Christophe Richez, Vincent Sobanski, François Maurier, Gaëtan Sauvetre, Hervé Levesque, Marie-Agnès Timsit, Nathalie Tieulié, Pauline Orquevaux, Boris Bienvenu, Matthieu Mahevas, Thomas Papo, Céline Lartigau-Roussin, Elodie Chauvet, Emilie Berthoux, Françoise Sarrot-Reynauld, Loïc Raffray, Marion Couderc, Nicolas Martin Silva, Noémie Jourde-Chiche, Nicolas Belhomme, Thierry Thomas, Vincent Poindron, Viviane Queyrel-Moranne, Juliette Delforge, Camille Le Ray, Emmanuelle Pannier, Xavier Mariette, Véronique Le Guern, Raphaèle Seror, Alexandra AUDEMARD-VERGER, Emmanuel AZZI, Béatrice BANNEVILLE, Antoine BAUDET, Constance BEAUDOUIN BAZIRE, Cristina BELIZNA, Alexandre Belot, Ygal BENHAMOU, Alice Berezné, Fanny BERNARD-GUERVILLY, Sabine BERTHIER, Holy BEZANAHARY, Lisa BIALE, Adrien BIGOT, Claire BLANCHARD-DELAUNAY, Anne CALAS, Julien CAMPAGNE, Pascal CATHEBRAS, Claire CAZALETS, Benjamin CHAIGNE, Olivia CHANDESRIS, Jérémy CHATELAIS, Emmanuel CHATELUS, Fleur COHEN, Bernard Combe, Céline COMPARON, Pascal COQUERELLE, Louise DAMIAN, Eric DAUGAS, Mathilde DE MENTHON, Claire DE MOREUIL, Estelle DELATTRE, Azeddine DELLAL, Catherine Deneux-Tharaux, Amélie DENIS, Camille DEPROUW, Emmanuelle DERNIS, Alban DEROUX, Sandra DESOUCHES, Philippe Dieudé, Guillaume DIREZ, Maxime Dougados, Marine DRIESSEN, Aurélie DU THANH, Laetitia DUNOGEANT, Cécile DURANT, Cécile-Audrey DUREL, Isabelle DURIEU, Florence EBOUE, Elisabeth Elefant, Olivier FAIN, Bruno FAUTREL, René-Marc FLIPO, Aline FRAZIER, Antoine FROISSART, Sophie GEORGIN-LAVIALLE, Elisabeth GERVAIS, Bertrand GODEAU, François Goffinet, Anne GOMPEL, Laure GOSSEC, Philippe GOUPILLE, Claire GRANGE, Constance GUILLAUD-DANIS, Eric HACHULLA, Sabine HOEFSLOOT, Aurélie HUMMEL, Patrick JEGO, Stéphanie JOBARD, Laurence JOSSELIN-MAHR, Marc LAMBERT, Vincent LANGLOIS, Delphine LARIVIERE, Claire LARROCHE, Augustin LATOURTE, Christian LAVIGNE, Thomas LE GALLOU, Gaëlle LEROUX, Jean Guillaume LETAROUILLY, Frédéric LIOTÉ, Laurence Loeuillet, Jonathan London, Valentine Loustau, Pierre LOZAC'H, Emmanuel MAHEU, Hélène MAILLARD, Hubert MAROTTE, Agathe MASSEAU, Arsène MEKINIAN, Sara Melboucy Belkhir, Corinne Miceli-Richard, Martin MICHAUD, Marc MICHEL, Olivier MORANNE, Chafika MORATI-HAFSAOUI, Guillaume MOULIS, Luc MOUTHON, Barbara NICOLAS, Jacky Nizard, Jérémy ORA, Rodérau OUTH, Elisabeth PASQUIER, Jean-Loup PENNAFORTE, Antoinette PERLAT, Hélène PETIT-BAUER, Evangeline PILLEBOUT, Jean-Maxime PIOT, Agnès PORTIER, Olivier Pourrat, Xavier PUECHAL, Gregory PUGNET, Manon REDONDIN, Alexis REGENT, Mélanie RORIZ, Laurent SAILLER, Léa SAVEY, Marc SCHERLINGER, Nicolas SCHLEINITZ, Jérémie Sellam, Loïc Sentilhes, Aude SERVAIS, Perrine SMETS, Christelle SORDET, Martin SOUBRIER, Katia STANKOVIC-STOJANOVIC, Geoffrey URBANSKI, Véronique VEIT, Emmanuelle WEBER, and Cécile YELNIK

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2023

16. Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study

Author

Anne Murarasu, Gaëlle Guettrot-Imbert, Véronique Le Guern, Cécile Yelnik, Viviane Queyrel, Nicolas Schleinitz, Nicole Ferreira-Maldent, Elisabeth Diot, Geoffrey Urbanski, Emmanuelle Pannier, Estibaliz Lazaro, Odile Souchaud-Debouverie, Pauline Orquevaux, Nicolas Belhomme, Nathalie Morel, Elodie Chauvet, François Maurier, Maëlle Le Besnerais, Noemie Abisror, Tiphaine Goulenok, Françoise Sarrot-Reynauld, Alban Deroux, Elisabeth Pasquier, Claire de Moreuil, Holy Bezanahary, Laurent Pérard, Nicolas Limal, Vincent Langlois, Anne Calas, Bertrand Godeau, Christian Lavigne, Eric Hachulla, Fleur Cohen, Ygal Benhamou, Loïc Raffray, Mathilde de Menthon, Nathalie Tieulié, Vincent Poindron, Luc Mouthon, Maddalena Larosa, Elisabeth Eléfant, Loic Sentilhes, Anna Molto, Catherine Deneux-Tharaux, Nathalie Costedoat-Chalumeau, Emmanuel Azzi, Béatrice Banneville, Antoine Baudet, Constance Beaudouin-Bazire, Cristina Belizna, Rakiba Belkhir, Alice Berezne, Emilie Berthoux, Sabine Berthier, Lisa Biale, Boris Bienvenu, Claire Blanchard-Delaunay, Pascal Cathebras, Claire Cazalets, Benjamin Chaigne, Olivia Chandesris, Jérémy Chatelais, Emmanuel Chatelus, Pascal Coquerelle, Marion Couderc, Juliette Delforge, Amélie Denis, Sandra Desouches, Philippe Dieudé, Guillaume Direz, Marine Driessen, Aurélie Du Thanh, Laetitia Dunogeant, Cécile Durant, Isabelle Durieu, Marc Fabre, Olivier Fain, René-Marc Flipo, Aline Frazier, Antoine Froissart, Sophie Georgin-Lavialle, Elisabeth Gervais, Anne Gompel, Laure Gossec, Phillipe Goupille, Claire Grange, Constance Guillaud-Danis, Aurélie Hummel, Moez Jallouli, Patrick Jego, Stéphane Jobard, Laurence Josselin-Mahr, Noémie Jourde-Chiche, Anne-Sophie Korganow, Marc Lambert, Delphine Lariviere, Claire Larroche, Céline Lartigau-Roussin, Augustin Latourte, Thomas Le Gallou, Gaëlle Leroux, Hervé Levesque, Frédéric Lioté, Jonathan London, Valentine Loustau, Emmanuel Maheu, Matthieu Mahevas, Hélène Maillard, Xavier Mariette, Hubert Marotte, Nicolas Martin-Silva, Nihal Martis, Agathe Masseau, Arsène Mekinian, Sara Melboucy-Belkhir, Martin Michaud, Marc Michel, Chafika Morati-Hafsaoui, Jacky Nizard, Jérémy Ora, Jean-Loup Pennaforte, Antoinette Perlat, Hélène Petit Bauer, Evangeline Pillebout, Jean-Maxime Piot, Agnès Portier, Gregory Pugnet, Manon Redondin, Alexis Regent, Christophe Richez, Mélanie Roriz, Laurent Sailler, Gaëtan Sauvêtre, Léa Savey, Vincent Sobanski, Christelle Sordet, Martin Soubrier, Katia Stankovic Stojanovic, Thierry Thomas, Marie-Agnès Timsit, and Vassilis Tsatsaris

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2022

17. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar

Subjects
medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Published
2022

18. Specific Follicular Helper T Cell Signature in Takayasu Arteritis

Author

A.C. Desbois, Boris Bienvenu, Nicolas Dérian, Valentin Quiniou, M Rosenzwag, David Klatzmann, P Bruneval, Maxime Samson, David Saadoun, H. Vallet, Anna Maciejewski-Duval, Cloé Comarmond, Pierre Fouret, Damien Sène, Jacques Pouchot, Fabien Koskas, P. Régnier, G. Darrasse-Jèze, A Lejoncour, Marlène Garrido, and Patrice Cacoub

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, Receptors, CXCR5, 0301 basic medicine, T Follicular Helper Cells, Receptors, Antigen, T-Cell, alpha-beta, Antigens, CD19, Giant Cell Arteritis, Programmed Cell Death 1 Receptor, Immunology, C-C chemokine receptor type 6, CXCR3, CD19, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Nitriles, Humans, Janus Kinase Inhibitors, Immunology and Allergy, Aorta, Aged, Cell Proliferation, Aged, 80 and over, 030203 arthritis & rheumatology, CD20, B-Lymphocytes, biology, Gene Expression Profiling, T-cell receptor, Middle Aged, Antigens, CD20, Takayasu Arteritis, CCL20, Pyrimidines, Tertiary Lymphoid Structures, 030104 developmental biology, Immunoglobulin G, biology.protein, Pyrazoles, Female, Antibody, Transcriptome, Immunologic Memory
Abstract

OBJECTIVE Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire. CONCLUSION We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

Published
2021

19. Systematic retrospective study of 64 patients with anti-Mi2 dermatomyositis: A classic skin rash with a necrotizing myositis and high risk of malignancy

Author

Sarah Guégan, Nathalie Costedoat-Chalumeau, Vincent Descamps, Emmanuel Bergot, G. Monseau, Yoland Schoindre, C. Martel, Stéphane Barete, Cristian Bulai Livideanu, Valérie Jooste, Aude Rigolet, Achille Aouba, Thierry Zenone, Hubert de Boysson, Emmanuelle Salort-Campana, Jean-Emmanuel Kahn, Sarah Leonard-Louis, Werner Stenzel, Baptiste Hervier, Sylvain Audia, Antoine Dossier, Nicolas Schleinitz, Eric Hachulla, Alain Meyer, Laurent Mortier, Marie Lacoste, Guillaume Moulis, Serge Madaule, Florian Perez, Kuberaka Mariampillai, Anne-Marie Bouvier, Yves Allenbach, Laurence Verneuil, Benjamin Terrier, Nicolas Champtiaux, Thomas Papo, Séverine Genot, Maxime Samson, Agathe Masseau, Thierry Maisonobe, Marie-Aleth Richard, Olivier Benveniste, Boris Bienvenu, François Maurier, Guillaume Lefèvre, Anne-Marie Piette, and O. Landon-Cardinal

Subjects
Adult, Male, medicine.medical_specialty, Risk of malignancy, MEDLINE, Dermatology, Risk Assessment, Dermatomyositis, Necrosis, Risk Factors, Neoplasms, medicine, Humans, Muscle, Skeletal, Aged, Autoantibodies, Retrospective Studies, Skin, business.industry, Incidence, Necrotizing myositis, Retrospective cohort study, Exanthema, Middle Aged, Prognosis, medicine.disease, Rash, Female, medicine.symptom, business, Mi-2 Nucleosome Remodeling and Deacetylase Complex
Published
2020

20. Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study

Author

Maël Heiblig, Marcela A. Ferrada, Matthew T. Koster, Thomas Barba, Mathieu Gerfaud-Valentin, Arsène Mékinian, Henrique Coelho, Gaelle Fossard, Fiorenza Barraco, Lionel Galicier, Boris Bienvenu, Pierre Hirsch, Guillaume Vial, Anne Blandine Boutin, Joris Galland, Guillaume Le Guenno, Adrien Bigot, Kenneth J. Warrington, Tanaz A. Kermani, Peter C. Grayson, Bhavisha A. Patel, David B. Beck, Yvan Jamilloux, Pierre Fenaux, and Pierre Sujobert

Subjects
Pyrimidines, Myelodysplastic Syndromes, Immunology, Nitriles, Janus Kinase Inhibitors, Pyrazoles, Skin Diseases, Genetic, Cell Biology, Hematology, Biochemistry, Retrospective Studies
Abstract

VEXAS syndrome (vacuoles in myeloid progenitors, E1 ubiquitin activating enzyme, X-linked, autoinflammatory manifestations and somatic) is an autoinflammatory condition caused by somatically acquired UBA1 mutations. Heiblig et al report on an international retrospective analysis of 30 patients with VEXAS syndrome treated with different Janus kinase (JAK) inhibitors, finding encouraging evidence supporting the use of the JAK1/2 inhibitor ruxolitinib with clinical remissions and reductions in steroid use seen in the majority of patients.

Published
2022

21. Performances de l’IRM musculaire pour le diagnostic des myopathies auto-immunes : étude prospective multicentrique (DARWIM)

Author

L.S. Léonard, B. Brihaye, Yoland Schoindre, D. Seilhean, G. Guy, Pascale Ghillani-Dalbin, Thierry Maisonobe, Olivier Lucidarme, Hendy Abdoul, J.L. Charuel, F. Foissac, J.F. Deux, Olivier Benveniste, G. Mercy, Y. Allenbach, Boris Bienvenu, Divi Cornec, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie Polyvalente et Oncologique = Service d'Imagerie Spécialisées et des Urgences [CHU Pitié-Salpêtrière] (SISU), Thérapeutiques substitutives du coeur et des vaisseaux (TSCV), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hôpital Foch [Suresnes], Service de Neuropathologie [CHU Pitié Salpêtrière], Service de Neurophysiologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU), Service d'Immunologie [CHU Pitié-Salpétrière], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), and Hôpital Saint-Joseph [Marseille]

Subjects
[SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine
Abstract

International audience

Published
2021

22. Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial

Author

Alexandra Audemard-Verger, Amélie Le Gouge, Vincent Pestre, Johan Courjon, Vincent Langlois, Marc-Olivier Vareil, Mathilde Devaux, Boris Bienvenu, Vincent Leroy, Radjiv Goulabchand, Léa Colombain, Adrien Bigot, Thomas Guimard, Youcef Douadi, Geoffrey Urbanski, Jean François Faucher, Laurence Maulin, Bertrand Lioger, Jean-Philippe Talarmin, Matthieu Groh, Joseph Emmerich, Sophie Deriaz, Nicole Ferreira-Maldent, Ann-Rose Cook, Céline Lengellé, Hélène Bourgoin, Arsène Mekinian, Achille Aouba, François Maillot, and Agnès Caille

Subjects
Adult, Interleukin 1 Receptor Antagonist Protein, Multidisciplinary, Treatment Outcome, SARS-CoV-2, Humans, Respiration, Artificial, COVID-19 Drug Treatment
Abstract

Objective We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. Methods In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Results Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference—21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). Conclusion This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Published
2021

23. Tocilizumab plus dexamethasone versus dexamethasone in patients with moderate-to-severe COVID-19 pneumonia: A randomised clinical trial from the CORIMUNO-19 study group

Author

Olivier Hermine, Xavier Mariette, Raphael Porcher, Felix Djossou, Yann Nguyen, Jean-Benoît Arlet, Laurent Savale, Jean Luc Diehl, Sophie Georgin-Lavialle, Jacques Cadranel, Gilles Pialoux, Karine Lacombe, Arsène Mekinian, Hélène Gros, Xavier Lescure, Jade Ghosn, Elisabeth Coupez, Kevin Grapin, Christophe Rapp, Marc Michel, Anne Lise Lecapitaine, Jean Marie Michot, Nathalie Costedoat-Chalumeau, Liem Binh Luong Nguyen, Luca Semerano, François Raffi, Claire Aguillar, Claire Rouzaud, Jacques Eric Gottenberg, Yves Hansmann, Boris Bienvenu, Jonathan London, Franklin Samou Fantchou, Felix Ackermann, Antoine Gros, Alexandre Morel, Nicolas Gambier, Damien Sène, Bruno Mégarbane, Elie Azoulay, Serge Bureau, Maxime Dougados, Joseph Emmerich, Muriel Fartoukh, Bertrand Guidet, Marc Humbert, Mathieu Mahevas, Frédéric Pène, Frédéric Schlemmer, Valérie Pourcher-Martinez, Annick Tibi, Gabriel Baron, Elodie Perrodeau, Stéphanie Baron, Gabriel Steg, Yazdan Yazdapanah, Tabassome Simon, Matthieu Resche-Rigon, Pierre-Louis Tharaux, Philippe Ravaud, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bicêtre, Université Paris-Saclay, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Hôtel-Dieu [Paris], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital Beaujon [AP-HP], Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), Université Sorbonne Paris Nord, CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Robert Ballanger [Aulnay-sous-Bois], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Américain de Paris, Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Compiègne-Noyon (CHCN), Centre Hospitalier Compiègne-Noyon, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Hôpital Cochin [AP-HP], Sorbonne Université (SU), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Avicenne [AP-HP], Hôtel-Dieu de Nantes, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Centre hospitalier Saint-Joseph [Paris], Les Hôpitaux Universitaires de Strasbourg (HUS), Université de Strasbourg (UNISTRA), Hôpital Saint-Joseph [Marseille], Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre Hospitalier de l'Ouest Guyanais Franck Joly [Saint-Laurent-du-Maroni, Guyane Française], Hôpital Foch [Suresnes], Centre Hospitalier de Versailles André Mignot (CHV), Hôpital privé d'Antony - Ramsay Santé (HPA-RS), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris Diderot - Paris 7 (UPD7), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Hopital Saint-Louis [AP-HP] (AP-HP), Université Paris-Est (UPE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], Agence Générale des Equipements et Produits de Santé [Paris] (AGEPS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Service de médecine interne [CHU Saint-Antoine], and Tharaux, Pierre-Louis

Subjects
[SDV] Life Sciences [q-bio], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], COVID-19, General Medicine, Randomized clinical trial, Tocilizumab+Dexamethasone, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial.Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979.Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively.Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn.Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

Published
2021

24. Valeur pronostique de la TEP-TDM au diagnostic et lors du suivi au cours de l’artérite à cellules géantes

Author

B. Durand-Bailloud, Sabine Mainbourg, Aurélie Daumas, Bernard Bonnotte, Laurent Perard, C. Bachmeyer, J.L. Alberini, C.A. Durel, Sébastien Humbert, Maxime Samson, H. De Boysson, Boris Bienvenu, Thomas Sené, A.C. Billet, and Eric Liozon

Subjects
Gastroenterology, Internal Medicine
Abstract

Introduction La TEP-TDM est de plus en plus utile pour faire le diagnostic d’arterite a cellules geantes (ACG), en particulier en cas de forme extra-cephalique. Sa performance diagnostique est excellente avec une sensibilite de 82 % et une specificite proche de 100 % [1] . Au cours du suivi, la place et les modalites d’interpretation de la TEP-TDM sont moins bien definis. L’objectif de notre travail etait de determiner si le degre d’hypermetabolisme vasculaire a la TEP-TDM, au diagnostic d’ACG et apres 3 a 12 mois de suivi, etait predictif de la survenue de rechute d’ACG. Patients et methodes Nous avons mene une etude retrospective multicentrique portant sur 53 patients atteints d’ACG avec atteinte des gros vaisseaux au diagnostic. Chaque patient avait eu une TEP-TDM au diagnostic (TEP no 1), et un controle dans les 3 a 12 mois suivant le diagnostic (TEP no 2). Pour chacun des 14 segments arteriels, le niveau d’hypermetabolisme vasculaire etait cote de facon semi-quantitative selon les recommandations internationales [2] : grade 0 en l’absence d’hypermetabolisme, grade 1 (SUV max arteriel SUV max hepatique). Le grade de fixation de chaque segment arteriel etait additionne pour obtenir un score nomme Total Vascular Score (TVS) qui variait de 0 a 42 points. Nous avons etudie le risque de survenue de rechute en fonction des TVS de la TEP no 1 et de la TEP no 2. La rechute etait definie comme la reapparition, apres une periode de remission d’au moins 3 mois, d’au moins un signe clinique d’ACG ou de PPR, ou d’un syndrome inflammatoire (CRP > 10 mg/L) pendant plus de 2 semaines consecutives sans autre cause que l’ACG et ayant conduit a majorer le traitement de l’ACG. Les resultats sont exprimes en mediane (espace interquartile) ou nombre (%) et compares par des tests de Mann–Whitney, Wilcoxon, Chi2 ou Fisher. Le risque de rechute a ete evalue par des courbes de Kaplan–Meier et les facteurs associes au risque de rechute ont ete analyses a l’aide de tests de log-rank. Resultats Cinquante-trois patients ont ete inclus dans cette etude, âges de 70 (63–75) ans, dans 79 % des cas de sexe feminin. La BAT etait positive dans 51 % des cas. Le TVS variait de 24 (18–32) points lors la TEP no 1 a 6,5 (0–14) points lors de la TEP no 2 (p 14 (p = 0,067). Pour la TEP no 2, nous avons analyse les 44 patients pour lesquels la TEP avait ete realisee en dehors d’un episode de rechute. Lors du suivi, un TVS superieur a 14 points ou 23 points etait associe a un risque de rechute de 50 % ou 67 % a 12 mois, et 67 % ou 100 % a 24 mois respectivement (p = 0,019 vs TVS ≤ 14 et p = 0,001 vs TVS ≤ 23 points respectivement). Discussion Nos donnees suggerent que la TEP realisee au cours du suivi de l’ACG est plus discriminante que celle realisee au diagnostic pour predire le risque de rechute. De plus, l’utilisation d’un score semi-quantitatif (TVS) permet d’en standardiser l’analyse et de determiner des seuils (≤ 14, 14 a 20, et > 20 points) pour predire le risque de rechute. Ces resultats sont concordants avec ceux de l’etude de Grayson et al. [3] qui rapportaient qu’un score vasculaire (PETVAS) superieur a 20 points etait predictif de la survenue de rechute au cours du suivi. Conclusion Un TVS > 14 points et a fortiori > 20 points lors d’une TEP de suivi realisee apres 3 a 12 mois de traitement est predictif de rechute au cours de l’ACG avec atteinte des gros troncs.

Published
2021

25. L’atteinte aortique au cours de la polychondrite chronique atrophiante

Author

Isabelle Marie, Jonathan Boutemy, Zahir Amoura, Laurent Arnaud, Boris Bienvenu, Hervé Levesque, and Maelle Le Besnerais

Subjects
030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, 030204 cardiovascular system & hematology
Abstract

Resume Objectif Evaluer la prevalence de l’atteinte aortique dans la polychondrite atrophiante (PCA) ; determiner les caracteristiques cliniques et evolutives des patients qui presentent une aortite, une ectasie et/ou un anevrisme aortique au cours de la PCA. Methodes Un angioscanner aortique a ete realise chez 172 patients atteints de PCA et suivis dans 3 centres medicaux. Resultats Une atteinte aortique a ete rapportee chez 11 patients (6,4 %) avec un delai median de survenue de 2 ans apres le diagnostic de PCA. L’angioscanner a mis en evidence la presence d’une aortite isolee (n = 2) ; il a ete retrouve chez les 9 autres patients une aortite et un anevrisme (n = 2) ou une ectasie aortique (n = 1), un anevrisme aortique (n = 4) ou une ectasie aortique (n = 2) isoles ; les lesions aortiques etaient localisees au niveau de l’aorte thoracique (n = 6), abdominale (n = 2) et thoraco-abdominale (n = 4). L’evolution chez ces patients a ete comme suit : resolution (n = 3), amelioration (n = 3), stabilisation (n = 4) ou degradation (n = 1) de la localisation aortique. Cinq patients ont rapporte une rechute de la localisation aortique ; un patient est decede des suites d’une rupture de l’anevrisme aortique abdominal. Les facteurs predictifs de deces lie aux complications aortiques etaient la presence d’une aortite a l’angioscanner et la vitesse de sedimentation plus elevee. Les parametres predictifs de rechute aortique etaient la presence d’une aortite a l’angioscanner et la localisation aortique abdominale. Conclusions Cette etude souligne la gravite des localisations aortiques au cours de la PCA. Par ailleurs, la mise en evidence de facteurs predictifs d’un pronostic pejoratif de l’atteinte aortique, incluant la panaortite et l’elevation de la VS, pourrait justifier l’instauration d’un traitement plus agressif chez ces patients.

Published
2018

26. Fourteen-day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study

Author

Laure Gallay, Viet-Thi Tran, Elodie Perrodeau, Nicolas Vignier, Matthieu Mahevas, Francesca Bisio, Emmanuel Forestier, Francois-Xavier Lescure, François-Xavier Lescure, Thibaut Fraisse, Diane Sanderink, Bertrand Lioger, Camille Boutrou, Anne - Laure Destrem, Pascal Gicquel, Martin Martinot, Jérémie Pasquier, Jean Reuter, Helene Desmurs-Clavel, Nicolas Benech, Boris Bienvenu, Guillemette Frémont, François Goehringer, Guillaume Chapelet, Olivier Grossi, Didier Laureillard, Cyrille Gourjault, Alexandre Lahens, Célia Azoulay, Nicolas Carlier, Gianpiero Tebano, Jérôme Pacanowski, Simone Tunesi, Nadège Lemaire, Laurent Bellec, Firouze Bani-Sadr, Marie Pichenot, Kevin Alexandre, Laurie Masse, Olivier Robineau, Camille Thorey, Sophie Deriaz, Julien Saison, Marie Gousseff, Laura Goehrs, Fanny Pommeret, and Université de Paris, Centre de Recherche Epidémiologie et Statistiques (CRESS UMR 1153) (CRESS UMR 1153)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, Pneumonia, Infectious Diseases, Relative risk, Corticosteroid, business, medicine.drug, Cohort study
Abstract

Objective To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. Methods We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. Results Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83–90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46–0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68–1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. Conclusions Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.

Published
2021

27. Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data

Author

Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, Sophie Ismaël, Cédric Laouénan, Jennifer Soulier, Oriane Puéchal, Eric D’Ortenzio, Yazdan Yazdanpanah, Laurence Maulin, Stéphanie Martinez, Diane Sanderink, Pascale Fialaire, Séverine Ansart, Lucas Perez, Anne - Laure Destrem, Chloé Moulin, Pascal Gicquel, Frédéric Rivière, Martin Martinot, Mahsa Mohseni Zadeh, Tomasz Chroboczek, Thibaut Challan Belval, Lionel Piroth, Thibault Sixt, Florian Moretto, André Cabié, Jérémie Pasquier, Ornella Cabras, Marine Morrier, Jean Reuter, Thomas Henin, Pierre Braquet, Helene Desmurs-Clavel, Arnaud Hot, Boris Bienvenu, Belkacem Asselate, Nicolas Vignier, Steve Nguala, Sylvain Diamantis, Guillemette Frémont, Pierre Louis Nivose, Mathilde Thiébaut, Benjamin Lefevre, Hélène Auge, Paul le Turnier, Naila Benkalfate, Olivier Grossi, Samuel Pineau, Elisa Demonchy, Julie Merindol, Claire Durand, Nathalie Tieulié, Viviane Queyrel, Didier Laureillard, Paul Loubet, Ségolène Greffe, Nathalie Dournon, Youssouf Mohamed Kassim, Cyrille Gourjault, Alexandre Lahens, Paul Legendre, Caroline Morbieu, Matthieu Mahevas, Giovanna Melica, Jean-Daniel Levièvre, Frédéric Schlemmer, Simone Tunesi, Claire Leblanc, Anne Bourgarit-Durand, Alexandre Bleibtreu, Gianpiero Tebano, Jérôme Pacanowski, Jean-Benoit Zabbe, Mathilde Devaux, Laurent Bellec, Marine Gosset-Woimant, Céleste Lambert, Maxime Hentzien, Amélie Servettaz, Kevin Alexandre, Manuel Etienne, Romain Leguillon, Marion Dollat, Rémi Lefrancois, Anne Pouvaret, Yvon Ruch, Yannick Dieudonné, Guillaume Martin-Blondel, Xavier Boumaza, Margaux Lafaurie, Macha Tetart, Adrien Lemaignen, Nicole Ferreira-Maldent, Amélie Duréault, Marie Gousseff, Claire Chantepie, Francesca Bisio, Fanny Pommeret, Emeline Colomba Blamble, and Claire Ara Somohano

Subjects
0301 basic medicine, Adult, Male, Microbiology (medical), medicine.medical_specialty, Adolescent, medicine.medical_treatment, Therapeutic evaluation, 030106 microbiology, Population, Severity of Illness Index, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Prednisone, Adrenal Cortex Hormones, Internal medicine, Observational study, Severity of illness, Medicine, Intubation, Corticosteroids, Humans, 030212 general & internal medicine, education, Aged, Mechanical ventilation, Aged, 80 and over, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Oxygen Inhalation Therapy, COVID-19, General Medicine, Middle Aged, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Pneumonia, C-Reactive Protein, Infectious Diseases, Original Article, Female, business, medicine.drug
Abstract

OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.

Published
2021
Full Text
View/download PDF

28. Thoracic involvement and imaging patterns in IgG4-related disease

Author

Boris Bienvenu, Antoinette Perlat, Mathieu Groh, Fleur Cohen, Paul Habert, Nicolas Schleinitz, Mikael Ebbo, Sylvain Audia, David Launay, Lea Gaigne, Romain Muller, Jean Gaubert, Julie Graveleau, Audrey Benyamine, Pascal Chanez, Grégory Pugnet, Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre hospitalier de Saint-Nazaire, Hôpital Foch [Suresnes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital Saint-Joseph [Marseille], Service de Pneumologie et Allergie - Hôpital Nord [Marseille], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Gestionnaire, HAL Sorbonne Université 5

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Diseases of the respiratory system, 03 medical and health sciences, Pleural disease, 0302 clinical medicine, medicine, Pericardium, Humans, Lymph node, Lung, Retrospective Studies, 030203 arthritis & rheumatology, RC705-779, business.industry, Mediastinum, Thorax, medicine.disease, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, IgG4-related disease, Radiology, Immunoglobulin G4-Related Disease, business, Tomography, X-Ray Computed, Interstitial Disease, Rheumatism
Abstract

ObjectiveImmunoglobulin G4-related disease (IgG4-RD) is a rare orphan disease. Lung, pleura, pericardium, mediastinum, aorta and lymph node involvement has been reported with variable frequency and mostly in Asian studies. The objective of this study was to describe thoracic involvement assessed by high-resolution thoracic computed tomography (CT) in Caucasian patients with IgG4-RD.MethodsThoracic CT scans before treatment were retrospectively collected through the French case registry of IgG4-RD and a single tertiary referral centre. CT scans were reviewed by two experts in thoracic imagery blinded from clinical data.Results48 IgG4-RD patients with thoracic involvement were analysed. All had American College of Rheumatology/European League Against Rheumatism classification scores ≥20 and comprehensive diagnostic criteria for IgG4-RD. CT scan findings showed heterogeneous lesions. Seven patterns were observed: peribronchovascular involvement (56%), lymph node enlargement (31%), nodular disease (25%), interstitial disease (25%), ground-glass opacities (10%), pleural disease (8%) and retromediastinal fibrosis (4%). In 37% of cases two or more patterns were associated. Asthma was significantly associated with peribronchovascular involvement (p=0.04). Among eight patients evaluated by CT scan before and after treatments, only two patients with interstitial disease displayed no improvement.ConclusionThoracic involvement of IgG4-RD is heterogeneous and likely underestimated. The main thoracic CT scan patterns are peribronchovascular thickening and thoracic lymph nodes.

Published
2021

29. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author

Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

Published
2021
Full Text
View/download PDF

30. Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis

Author

Philippe Saas, Boris Bienvenu, Sylvain Audia, Georges Tarris, François Maurier, T. Ghesquiere, Malika Trad, Benjamin Terrier, Claire Gerard, Marc Corbera-Bellalta, Marion Ciudad, Bernard Bonnotte, Hervé Devilliers, Pierre Charles, Coraline Genet, Maria C. Cid, Marine Thébault, Loïc Guillevin, Pierre-Henry Gabrielle, Maxime Samson, Eric Liozon, Kim Heang Ly, Hélène Greigert, Catherine Creuzot-Garcher, Valérie Quipourt, Claudie Cladière, Sethi Ouandji, Laurent Martin, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hospital Clínic de Barcelona, University of Barcelona, CHU Limoges, Hôpitaux Privés de Metz (HPMetz), Hôpital Saint-Joseph [Marseille], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mutualiste de Montsouris (IMM), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Julien, Sabine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, chemical and pharmacologic phenomena, 030204 cardiovascular system & hematology, Flow cytometry, tocilizumab, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Immune system, Immunology and Allergy, Medicine, skin and connective tissue diseases, Interleukin 6, General Nursing, 030203 arthritis & rheumatology, biology, medicine.diagnostic_test, giant cell arteritis, business.industry, FOXP3, hemic and immune systems, RC581-607, medicine.disease, 3. Good health, Blockade, Treg, Giant cell arteritis, chemistry, interleukin‐6, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Original Article, Immunologic diseases. Allergy, business, After treatment
Abstract

Objectives To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab. Methods Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab (n = 20) or glucocorticoids (n = 23). Treg percentage and phenotype were assessed by flow cytometry. Suppressive function of Treg was assessed by measuring their ability to inhibit effector T‐cell (Teff) proliferation and polarisation into Th1 and Th17 cells. Results Treg (CD4+CD25highFoxP3+) frequency in total CD4+ T cells was decreased in active GCA patients when compared to controls (2.5% vs. 4.7%, P, In this study, we demonstrated quantitative and functional disruptions in the regulatory immune response of patients with giant cell arteritis, resulting in increased proliferation and Th17 polarization of effector T cells. In addition, our results suggest that, through a specific blockade of the IL‐6 pathway, tocilizumab associated with glucocorticoids restores a better quantitative and qualitative Treg immune response than glucocorticoids alone. GCA, giant cell arteritis. Teff, effector T‐cells; Th17, T helper‐17 cells; Treg, regulatory T‐cells.

Published
2021

31. Immunogenicity and Reactogenicity of Heterologous and Homologous mRNA-1273 and BNT162b2 Vaccination: A Multicenter Non-Inferiority Randomized Trial

Author

Cécile Janssen, Marine Cachanado, Laetitia Ninove, Marie Lachatre, Jocelyn Michon, Olivier Epaulard, Zoha Maakaroun-Vermesse, Christian Chidiac, Bruno Laviolle, Hugues Aumaitre, Ady Assaf, Karine Lacombe, Catherine Schmidt-Mutter, Elisabeth Botelho-Nevers, Magali Briere, Thomas Boisson, Paul Loubet, Boris Bienvenu, Olivier Bouchaud, Amel Touati, Christine Pereira, Alexandra Rousseau, Laurence Berard, Melissa Montil, Xavier de Lamballerie, Tabassome Simon, Odile Launay, and The ARNCOMBI Study Group

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2021

32. Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial

Author

Vincent Dubée, Pierre-Marie Roy, Bruno Vielle, Elsa Parot-Schinkel, Odile Blanchet, Astrid Darsonval, Caroline Lefeuvre, Chadi Abbara, Sophie Boucher, Edouard Devaud, Olivier Robineau, Patrick Rispal, Thomas Guimard, Emma d’Anglejean, Sylvain Diamantis, Marc-Antoine Custaud, Isabelle Pellier, Alain Mercat, Antoine Brangier, Philippe Codron, Jean Michel Lemée, Virginie Pichon, Robin Dhersin, Geoffrey Urbanski, Christian Lavigne, Roxane Courtois, Hélène Danielou, Jonathan Lebreton, Rémi Vatan, Nicolas Crochette, Jean-Baptiste Lainé, Lucia Perez, Sophie Blanchi, Hikombo Hitoto, Louis Bernard, François Maillot, Sylvain Marchand Adam, Jean-Philippe Talarmin, Emeline Gaigneux, Pauline Motte-Vincent, Marine Morrier, Dominique Merrien, Yves Bleher, Maxime Flori, Amélie Ducet-Boiffard, Orane Colin, Ronan Février, Pauline Thill, Macha Tetart, François Demaeght, Barthelemy Lafond-Desmurs, Maxime Pradier, Agnes Meybeck, Marjorie Picaud, Thierry Prazuck, Guillaume Chapelet, Agnès Rouaud, Paul Le Turnier, Simon Sunder, Aurélien Lorleac'h, Christophe Dollon, Antoine Jacquet, Francois Le Vely, Pierre Gazeau, Séverine Ansart, Hélène Roger, François Laterza, Rodolphe Buzelé, Fella Tahmi, Raphael Lepeule, Karine Lacombe, Bénédicte Lefebvre, Thomas Célarier, Amandine Gagneux-Brunon, Elisabeth Botelho-Nevers, Marc Bernard, Camille Garnier, Morgane Mourguet, Gregory Pugnet, Sara Vienne-Noyes, Guillaume Martin-Blondel, Pierre Delobel, Gaspard Grouteau, Alexa Debard, Laurent Guilleminault, Pauline Arias, Catherine Chakvetadze, Clara Flateau, Aude Kopp, Alain Putot, Jeremy Barben, Suzanne Mouries Martin, Valentine Nuss, Lionel Piroth, Yann-Erick Claessens, Veronique Hentgen, Martin Martinot, Maxime Bach-Bunner, Thomas Bonijoly, Simon Gravier, Jean-Marc Michel, Mathilde Andreu, Mélanie Roriz, Aurélie Baldolli, Julia Brochard, Olivier Grossi, Samuel Pineau, Josselin Brisset, Edouard Desvaux, Guillaume Gondran, Jean-François Faucher, Paul-Antoine Quesnel, Holy Bezanahary, Clément Danthu, Blandine Gutierrez, Kim Ly, Yannick Simonneau, Anne Cypierre, Pauline Pinet, Hélène Durox, Sophie Ducroix-Roubertou, Claire Genet, Guillaume Beraud, Gwenael Le Moal, Blandine Rammaert, Jean-Philippe Lanoix, Claire Andrejak, Cédric Joseph, Sandrine Soriot-Thomas, Robin Dhote, Sébastien Abad, Ruben Benainous, Jean-François Boitiaux, Guillaume Briend, Celine Gonfroy, Stanislas Harent, Aurore Lagrange, Alina Tone, Laura Wayenberg, Sophie Desoutter, Nicolas Ettahar, Thomas Gey, Vincent Leroy, Sacha Gaillard, Andrea Toma, Amaury Broussier, Sandrine Etienne, Yann Spivac, Benoit Martha, Nathalie Roch, Pierre Diaz, Danièle N’guyen Baranoff, Stanislas Rebaudet, François Jourda, Valérie Zeller, Boris Bienvenu, Arnaud Boyer, Marie Briet, Bertrand Guidet, Patrick Mismetti, Eric Vicaut, Olivier Sanchez, Philippe Girard, Antoine Elias, Francis Couturaud, Béatrice Gable, Sybille Lazareff, Loïc Carballido, Catherine Hue, Jean-Marie Chrétien, Adrien Goraguer, Lucie van Eeckhoutte, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Pharmacie [CHU d'Angers], Laboratoire de virologie [CHU Angers], Département de Pharmacologie-Toxicologie [CHU Angers], Centre Hospitalier René Dubos [Pontoise], Centre Hospitalier Tourcoing, Service de Médecine Interne [Agen], Centre Hospitalier d'Agen, Centre Hospitalier Départemental Vendée (CHDV), Centre Hospitalier de Versailles André Mignot (CHV), Groupe Hospitalier Sud, Université d'Angers (UA), HYCOVID study group, HYCOVID investigators, Angers University Hospital, Cholet Hospital, Laval Hospital, Le Mans Hospital, Tours University Hospital, Quimper Hospital, La Roche sur Yon Hospital, Tourcoing Hospital, Orléans Hospital, Nantes University Hospital, Niort Hospital, Lorient Hospital, Brest University Hospital, Cherbourg Hospital, Saint-Brieuc Hospital, Créteil – APHP University Hospital, Saint-Antoine – APHP University Hospital, Saint-Etienne University Hospital, Toulouse University Hospital, Melun Hospital, Dijon University Hospital, Princesse Grace – Monaco Hospital, Versailles Hospital, Colmar Hospital, Agen-Nerac Hospital, Caen University Hospital, Saint-Nazaire Hospital, Nantes – Confluent Hospital, Limoges University Hospital, Poitiers University Hospital, Amiens University Hospital, Bobigny – APHP University Hospital, Cergy-Pontoise Hospital, Valencienne Hospital, Valencienne – Clinique Tessier Hospital, Henri-Mondor – APHP University Hospital, Chalon-sur-Saône Hospital, Marseille European Hospital, Auxerre Hospital, Diaconnesses Croix-Saint-Simon Hospital, Marseille – Saint Joseph Hospital, Composition of the HYCOVID management team, Steering committee, Independant data safety and monitoring board, Independent adjudication of clinical events committee, Study management Coordination, Data management., Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service des maladies infectieuses et tropicales [CHU Angers], and Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Interquartile range, Intensive care, Internal medicine, medicine, Clinical endpoint, 030212 general & internal medicine, education, Severe acute respiratory syndrome coronavirus 2, education.field_of_study, Coronavirus disease 2019, business.industry, Hydroxychloroquine, General Medicine, Placebo-controlled, 3. Good health, Infectious Diseases, Relative risk, business, medicine.drug
Abstract

Objectives To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. Trial registration ClinicalTrials.gov Identifier: NCT04325893 ( https://clinicaltrials.gov/ct2/show/NCT04325893 ).

Published
2020

33. Aortic involvement in relapsing polychondritis

Author

Maelle Le Besnerais, Jonathan Boutemy, Laurent Arnaud, Hervé Levesque, Zahir Amoura, Isabelle Marie, Boris Bienvenu, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire Géomatériaux (DGCB-LGM), École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Computed Tomography Angiography, [SDV]Life Sciences [q-bio], Comorbidity, 030204 cardiovascular system & hematology, Risk Assessment, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, Aortic aneurysm, 0302 clinical medicine, Aneurysm, Rheumatology, Predictive Value of Tests, medicine.artery, Ectasia, Prevalence, medicine, Humans, Polychondritis, Relapsing, ComputingMilieux_MISCELLANEOUS, Aortitis, Relapsing polychondritis, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Academic Medical Centers, Aorta, medicine.diagnostic_test, business.industry, Abdominal aorta, Middle Aged, Prognosis, medicine.disease, 3. Good health, Surgery, Survival Rate, Erythrocyte sedimentation rate, cardiovascular system, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, business, Aortic Aneurysm, Abdominal, Dilatation, Pathologic
Abstract

Objective To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm. Methods One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers. Results Eleven patients (6.4%) had aortic involvement, occurring within a median time of 2 years after RP diagnosis. CT-scan showed isolated aortitis ( n = 2); the 9 other patients exhibited: aortitis and aortic aneurysm ( n = 2) or ectasia ( n = 1), isolated aortic aneurysm ( n = 4) or ectasia ( n = 2); aortic localizations were as follows: thoracic ( n = 6), abdominal ( n = 2), thoracic and abdominal ( n = 4) aorta. Patients exhibited: resolution ( n = 3) improvement ( n = 3), stabilization ( n = 4) or deterioration ( n = 1) of aortic localization. Five patients experienced recurrence of aortic localization; one patient died of aortic abdominal aneurysm rupture. Predictive factors of death related to aortic complications were: aortitis on CT-scan, higher median levels of erythrocyte sedimentation rate. Predictive parameters of aortic relapses were: aortitis on CT-scan and involvement of the abdominal aorta. Conclusions This study underlines that aortic involvement is severe in RP. Furthermore, we suggest that RP patients exhibiting poor prognostic factors, including panaortitis and higher values of ESR, may require more aggressive therapy.

Published
2018

34. Rapid Push vs Pump-Infused Subcutaneous Immunoglobulin Treatment: a Randomized Crossover Study of Quality of Life in Primary Immunodeficiency Patients

Author

Sylvie Brice, Dominique Lachaud, Anne-Laure Fauchais, Pierre Miossec, Jean-Charles Crave, Pierre Clerson, Grégoire Cozon, Françoise Renon-Carron, Jean-François Viallard, Cyrille Hoarau, Yann Fardini, Boris Bienvenu, Daniel Antier, Yves Mataix, Eric Hachulla, Antoine Alix, and Stéphanie Tamisier

Subjects
0301 basic medicine, Adult, Male, Every other day, home treatment, Immunology, Immunoglobulins, Subcutaneous immunoglobulin, Infusions, Subcutaneous, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Quality of life, medicine, Clinical endpoint, Immunology and Allergy, Humans, Syringe, Infusion Pumps, Aged, Subcutaneous Infusions, Primary immunodeficiency, Cross-Over Studies, business.industry, Immunologic Deficiency Syndromes, rapid push, Middle Aged, medicine.disease, Crossover study, PID immunoglobulin replacement therapy, 030104 developmental biology, Treatment Outcome, Anesthesia, Immunoglobulin G, Quality of Life, Original Article, Female, business, 030215 immunology
Abstract

Purpose Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient’s life quality index (LQI). Methods This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%. Results Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p = 0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump. Conclusions Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician’s armamentarium which is preferred by some patients and is cost-effective. ClinicalTrials.gov Identifier NCT02180763 Clinical Implications Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week. Capsule Summary This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician’s armamentarium.

Published
2018

35. Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis)

Author

Pascal Cathébras, Stéphanie Baillif, Laurent Kodjikian, Laurent Perard, Pierre-Loïc Cornut, Pierre Manoli, Sylvie Bin, Frédéric Mouriaux, Bahram Bodaghi, Sophie Rivière, Emmanuel Héron, Frédéric Chiambaretta, Neila Sedira, Christelle Schneider, Priscille Ollé, Pierre Grumet, David Saadoun, Marc André, Nathalie Tieulie, Marc Labetoulle, Audrey de Parisot, Yvan Jamilloux, Alain M. Bron, Pascal Sève, Philip Bielefeld, Evelyne Decullier, Christiane Broussolle, Stéphanie Vicente, Nicolas Bonin, Grégory Pugnet, Marie-Hélène Errera, Boris Bienvenu, Hospices Civils de Lyon (HCL), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Hôpital Saint Joseph, Clinique du Val d'Ouest, Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Pierre-Paul Riquet Hospital, Centre Hospitalier Universitaire de Purpan (CHU Purpan), North Hospital, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital l'Archet, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Department of Ophthalmology, CHU Pontchaillou [Rennes], and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)

Subjects
Adult, Male, medicine.medical_specialty, Tuberculosis, diagnosis, etiology, Immunology, Tuberculin, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Humans, Immunology and Allergy, Prospective Studies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030203 arthritis & rheumatology, medicine.diagnostic_test, Diagnostic Tests, Routine, business.industry, Lumbar puncture, Complete blood count, Middle Aged, standardized strategy, medicine.disease, 3. Good health, recommendations, uveitis, 030221 ophthalmology & optometry, Etiology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, epidemiology, Sarcoidosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Uveitis
Abstract

International audience; [u]PURPOSE:[/u] ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. [u]METHODS:[/u] ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. [u]RESULTS:[/u] Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon(R) (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. [u]CONCLUSION:[/u] Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.

Published
2018

36. Diagnostic value of quantitative assessment of cardiac 18F-fluoro-2-deoxyglucose uptake in suspected cardiac sarcoidosis

Author

Cédric Desmonts, Alain Manrique, Damien Legallois, Denis Agostini, Gérard Zalcman, Emmanuel Bergot, Adrien Lebasnier, and Boris Bienvenu

Subjects
medicine.diagnostic_test, business.industry, Deoxyglucose, Coefficient of variation, Curve analysis, General Medicine, Gold standard (test), Cardiac sarcoidosis, 030204 cardiovascular system & hematology, medicine.disease, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Positron emission tomography, cardiovascular system, medicine, Quantitative assessment, Radiology, Nuclear Medicine and imaging, Sarcoidosis, business, Nuclear medicine
Abstract

The identification of cardiac sarcoidosis is challenging as there is no gold standard consensually admitted for its diagnosis. The aim of this study was to evaluate the diagnostic value of the assessment of cardiac dynamic 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET/CT) and net influx constant (Ki) in patients suspected of cardiac sarcoidosis. Data obtained from 30 biopsy-proven sarcoidosis patients suspected of cardiac sarcoidosis who underwent a 50-min list-mode cardiac dynamic 18F-FDG PET/CT after a 24 h high-fat and low-carbohydrate diet were analyzed. A normalized coefficient of variation of quantitative glucose influx constant, calculated as the ratio: standard deviation of the segmental Ki (min−1)/global Ki (min−1) was determined using a validated software (Carimas® 2.4, Turku PET Centre). Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare criteria. Receiving operating curve analysis was performed to determine sensitivity and specificity of cardiac dynamic 18F-FDG PET/CT analysis to diagnose cardiac sarcoidosis. Six out of 30 patients (20%) were diagnosed as having cardiac sarcoidosis. Myocardial glucose metabolism was significantly heterogeneous in patients with cardiac sarcoidosis who showed significantly higher normalized coefficient of variation values compared to patients without cardiac sarcoidosis (0.513 ± 0.175 vs. 0.205 ± 0.081; p = 0.0007). Using ROC curve analysis, we found a cut-off value of 0.38 for the diagnosis of cardiac sarcoidosis with a sensitivity of 100% and a specificity of 91%. Our results suggest that quantitative analysis of cardiac dynamic 18F-FDG PET/CT could be a useful tool for the diagnosis of cardiac sarcoidosis.

Published
2018

37. Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A Multicenter Retrospective Study in 13 Adult Patients and Literature Review

Author

A. Hot, Gilles Grateau, Cécile-Audrey Durel, Hubert de Boysson, Boris Bienvenu, Achille Aouba, Sophie Georgin-Lavialle, Geoffrey Urbanski, Laurent Messer, Eric Hachulla, Pierre Quartier, Nicolas Rouanes, Samuel Deshayes, Stéphane Klein, Thomas Le Gallou, and Sylvain Audia

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Adolescent, Interleukin-1beta, Immunology, Antibodies, Monoclonal, Humanized, Infections, Weight Gain, 03 medical and health sciences, 0302 clinical medicine, Text mining, Rheumatology, Internal medicine, Genotype, medicine, Humans, Immunology and Allergy, Precision Medicine, Child, Retrospective Studies, 030203 arthritis & rheumatology, Anakinra, Mevalonate kinase deficiency, business.industry, Remission Induction, Antibodies, Monoclonal, Interleukin, Retrospective cohort study, Drug Tolerance, medicine.disease, Injection Site Reaction, Blockade, Interleukin 1 Receptor Antagonist Protein, Canakinumab, Treatment Outcome, 030104 developmental biology, Antirheumatic Agents, Child, Preschool, Female, France, Chemical and Drug Induced Liver Injury, Mevalonate Kinase Deficiency, business, medicine.drug
Abstract

Objective.To report efficacy and tolerance of interleukin 1 blockade in adult patients with mevalonate kinase deficiency (MKD).Methods.We retrospectively collected data on 13 patients with MKD who had received anakinra (n = 10) and canakinumab (n = 7).Results.Anakinra resulted in complete or partial remission in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to canakinumab led to partial remission. Canakinumab resulted in complete or partial remission in 3/7 and 4/7 patients, respectively.Conclusion.These data support frequent partial responses, showing a better response with canakinumab. The genotype and therapeutic outcomes correlation should help in the personalization of treatment.

Published
2018

38. Tolérance et efficacité des thérapies ciblées prescrites hors AMM au cours des maladies auto-immunes systémiques réfractaires : données des 100 premiers patients inclus dans le registre TATA (TArgeted Therapy in Autoimmune Diseases)

Author

J.F. Kleinmann, Renaud Felten, Marie-Elise Truchetet, G. Vial, Christophe Richez, V. Devauchelle Pensec, Zahir Amoura, Aurélien Guffroy, A. Chaudier, L. Bouillet, Benjamin Terrier, R. Seror, E. Hachulla, J.-E. Gottenberg, Alain Meyer, A. Leurs, M. Jouvray, Sébastien Ottaviani, Vincent André, D. Cornec, E. Gaigneux, A. Saunier, Christelle Sordet, Julien Henry, M. Gatfosse, Claire Larroche, Emmanuel Chatelus, Arsène Mekinian, H. Nielly, M. Ete, Xavier Mariette, Pierre Quartier, Martin Michaud, S. Ahmed Yahia, A. Poulet, G. Baulier, R. Jaussaud, T. Moulinet, Y. Allenbach, Boris Bienvenu, A. Dellal, Patrice Cacoub, M. Desmurs, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Oust de France (CeRAINO), F-59000, Lille, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Estación Biológica de Doñana (EBD), and Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)

Subjects
Rheumatology, [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2021

39. Clinical Efficacy of JAK Inhibitors in Patients with Vexas Syndrome: A Multicenter Retrospective Study

Author

Pierre Fenaux, Marcela A. Ferrada, Fiorenza Barraco, Kenneth J. Warrington, Mathieu Gerfaud-Valentin, Pierre Sujobert, Pierre Hirsch, Lionel Galicier, Maël Heiblig, Guillaume Le Guenno, Bhavisha A Patel, Matthew J. Koster, Thomas Barba, Gaelle Fossard, Henrique Coelho, Peter C. Grayson, Anne Blandine Boutin, Adrien Bigot, David B. Beck, Arsène Mekinian, Tanaz A. Kermani, Guillaume Vial, Yvan Jamilloux, and Boris Bienvenu

Subjects
medicine.medical_specialty, business.industry, Internal medicine, Immunology, medicine, Retrospective cohort study, In patient, Cell Biology, Hematology, Clinical efficacy, business, Biochemistry
Abstract

Background VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is due to a somatically acquired mutation of the E1-ubiquitin ligase UBA1, leading to the expression of a catalytically impaired isoform in myeloid cells. VEXAS syndrome combines severe auto-inflammatory manifestations and is frequently associated with myeloid neoplasia (MN). The outcome of VEXAS is poor, and most patients require high dose corticosteroids to reduce inflammation (Bourbon et al. Blood 2021). Therapeutic options besides steroids are currently limited in those patients. In this multicenter retrospective study, we report some clinical efficacy of JAK inhibitors (JAKi) in VEXAS patients. Patients We analyzed retrospectively 24 UBA1 mutated patients (Met41 or previously reported alternative splicing site) treated with JAKi (11 with ruxolitinib (RUXO), 11 with tofacitinib (TOFA), 1 with baricitinib, 1 with upadicitinib) in 7 French, 1 Portugese and 2 US centers. Complete clinical (CCR) and complete biological response (CBR) were defined as complete resolution of clinical symptoms and normalization of inflammation markers (C reactive protein, CRP) respectively. Partial clinical (PCR) and biological (PBR) response were defined by reduction of at least 50% of clinical or inflammation markers, respectively. Results All 24 patients were males with a median age at VEXAS diagnosis of 72 years [range 54-89]. Thirteen had documented myeloid neoplasia (MN) (1 CMML-0, 1 other MDS/MPN, 10 MDS). Clinical manifestations at VEXAS diagnosis include skin involvement (87.5%), arthritis or arthralgia (83.3%), vasculitis (37.5%), fever (75%), ocular manifestations (29.2%) and pulmonary infiltrates (41.6%). IPSS-R was very low/low/intermediate in 8/3/2 cases respectively. Median time between first VEXAS related clinical manifestations and JAKi onset was 2.45 years [0.15-5.45]. Prior to JAKi onset, patients had received a median of 2.5 immunosuppressive/immunomodulatory treatments [range 0-9]. After 1 month, 12/24 (50%) patients had achieved clinical and/or biological response. CCR and CBR was achieved in 7/11 (64%) and 6/11 (54%) patients treated with RUXO, and in 3/13 (23%) and 2/13 (15%) patients treated with other JAKi (figure A). After 3 months, CCR and CBR was 100% and 80% (10 evaluable patients) in the RUXO group as compared to 25% and 25 % in patients treated with other JAKi (8 evaluable patients) (p=0.0036 et 0.0055 respectively, figure B). RUXO efficacy was similar in patients with (n=9) or without (n=2) associated MN. In RUXO treated patients, median CRP and steroid dose reduction was 72.5% [range 21.5- 99.5] and 66.25% [range 0-75] respectively at 3 months. With a median follow-up of 4 months [range 1.4-12], only 1 RUXO treated patient had lost response, whereas median time to next of treatment was 3.4 months with other JAKi (figure C). Of the 13 patients with MN, 7 were RBC transfusion dependent at JAKi onset (6 with RUXO, 1 with other JAKi). Four of 6 patients treated with RUXO achieved RBC transfusion independence at 3 months, but not the patient treated with other JAKi. Regarding safety, severe adverse events were reported in 6 patients: 3 deep vein thrombosis, (2 with TOFA/1 with RUXO), 1 pneumonia (RUXO), 1 enterohemorrhagic E. Coli infection (RUXO), and 1 lethal legionellosis (TOFA)). Conclusion Ruxolitinib (and less often other JAK inhibitors used in this study) provides rapid response in most VEXAS patients, allowing in two third of the cases corticosteroid dose reduction/withdrawal and RBC transfusion independence in 4/6 patients with MN who were initially transfusion dependent. Those retrospective preliminary results, with limited follow up, must be interpreted with caution and will be updated at the meeting. The effect of RUXO on VEXAS patients with concomitant MN will soon be studied prospectively in a Groupe Francophone des Myélodysplasies (GFM) clinical study. Figure 1 Figure 1. Disclosures Galicier: Novartis Pharma Sas, Sanofi Aventis France: Consultancy; Lilly France, Baxalta France, Sanofi Aventis France Sas: Other: Payments as Speaker for Educational Program; Shire France SA, Janssen-Cilag, Pfizer Sas: Other: Invitation to Congress. Hirsch: Novartis Pharma: Consultancy; Daiichi Sankyo Oncology: Consultancy. Warrington: Eli Lilly: Research Funding; Kiniksa: Research Funding. Fenaux: Novartis: Honoraria, Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene/BMS: Honoraria, Research Funding; Syros Pharmaceuticals: Honoraria.

Published
2021

40. Restauration de la réponse T régulatrice après traitement par tocilizumab au cours de l’artérite à cellules géantes

Author

Bernard Bonnotte, L. Guillevin, H. Greigert, François Maurier, Maxime Samson, Boris Bienvenu, Benjamin Terrier, K.H. Ly, Marion Ciudad, Hervé Devilliers, Pierre-Emmanuel Charles, and Sylvain Audia

Subjects
030203 arthritis & rheumatology, 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Gastroenterology, Internal Medicine
Abstract

Introduction La reponse lymphocytaire T est perturbee au cours de l’arterite a cellules geantes (ACG). Les lymphocytes T (LT) recrutes au sein de la paroi arterielle se polarisent en LT helper (Th)-1 et Th17 produisant respectivement de l’IFN-γ et de l’IL-17. Contrastant avec cet exces de LT pro-inflammatoires, il existe au cours de l’ACG un deficit quantitatif en lymphocytes T regulateurs (Treg) [1] , [2] . Cependant, peu de donnees sont disponibles concernant les caracteristiques fonctionnelles des Treg au cours de l’ACG et leur evolution apres traitement par corticoides ou tocilizumab (TCZ). Patients et methodes Des prelevements sanguins ont ete obtenus chez 43 patients au moment du diagnostic d’ACG et apres 3 mois de traitement par prednisone (n = 23) ou prednisone + TCZ (n = 20). Des prelevements identiques ont ete realises chez 40 sujets controles apparies pour l’âge, ne recevant aucun traitement anti-inflammatoire ou immunosuppresseur, etant indemnes de pathologie infectieuse, auto-immune ou neoplasique connue et ayant une CRP Resultats L’etude quantitative a confirme, qu’avant traitement, le pourcentage de Treg (CD4 + CD25highFoxP3 + ) etait diminue chez les patients atteints d’ACG comparativement aux controles (2,5 % vs 4,7 %; p [2] . Le pourcentage de cette sous-population de Treg etait augmente au cours de l’ACG comparativement aux controles (23 % vs 10 % ; p = 0,0096) et se corrigeait apres traitement par prednisone et TCZ (p = 0,049) mais pas apres traitement par prednisone seule (p = 0,788). L’etude fonctionnelle des Treg a montre qu’en comparaison aux Treg de sujets sains, les Treg des patients atteints d’ACG active inhibaient significativement moins la proliferation des LT effecteurs. En presence de TCZ, les Treg des patients ACG retrouvaient le meme pouvoir immunosuppressif que les Treg temoins. Afin d’eliminer l’hypothese d’une resistance des T effecteurs des patients ACG aux Treg et non d’une perte de capacite suppressive par les Treg, nous avons montre que les LT effecteurs des patients ACG restaient sensibles a l’action des Treg. En effet, les Treg temoins inhibaient la proliferation des LT effecteurs des patients ACG. Les Treg ont une capacite suppressive mais sont aussi capables de modifier la differenciation des LT helpers. Alors que les Treg des sujets controles n’avaient pas d’effet significatif sur la polarisation des LT effecteurs en Th17, les Treg des patients atteints d’ACG induisaient une augmentation de 50 % des LTh17 qui disparaissait apres ajout de TCZ dans les cultures. De plus, la production d’IL-17 par les Treg des patients atteints d’ACG etait plus elevee par rapport a celle des Treg des sujets sains (16,8 % vs 4,6 % ; P = 0,048). Le traitement par dexamethasone d’arteres temporales atteintes d’ACG cultivees ex vivo pendant 5 jours induisait une diminution de la transcription des genes de l’IL-6 et de FoxP3, ce qui explique probablement la diminution de Treg chez les patients ACG sous corticotherapie. A l’inverse, le TCZ, qui bloque le recepteur de l’IL-6, ne modifiait pas le niveau d’expression des genes de l’IL-6 et de FoxP3, probablement car la perte d’expression de l’exon-2 est liee a un epissage alternatif et non pas a des modifications transcriptionnelles. Conclusion Les resultats de cette etude montrent qu’il existe d’importantes perturbations de la fonction T regulatrice au cours de l’ACG : la quantite de Treg est diminuee et leurs capacites fonctionnelles sont alterees. Ce deficit quantitatif et fonctionnel en Treg est corrige apres blocage de la signalisation de l’IL-6 par le TCZ, ce qui n’est pas le cas apres corticotherapie seule. Cette derniere aggrave meme le deficit quantitatif en Treg, ce qui pourrait expliquer la survenue de rechutes lors du sevrage de la corticotherapie.

Published
2020

41. Adding Azathioprine to Remission-Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors

Author

Xavier, Puéchal, Christian, Pagnoux, Gabriel, Baron, Thomas, Quémeneur, Antoine, Néel, Christian, Agard, François, Lifermann, Eric, Liozon, Marc, Ruivard, Pascal, Godmer, Nicolas, Limal, Arsène, Mékinian, Thomas, Papo, Anne-Marie, Ruppert, Anne, Bourgarit, Boris, Bienvenu, Loïck, Geffray, Jean-Luc, Saraux, Elisabeth, Diot, Bruno, Crestani, Xavier, Delbrel, Laurent, Sailler, Pascal, Cohen, Véronique, Le Guern, Benjamin, Terrier, Matthieu, Groh, Claire, Le Jeunne, Luc, Mouthon, Philippe, Ravaud, Loïc, Guillevin, and R, Meckenstock

Subjects
Adult, Male, medicine.medical_specialty, Exacerbation, Immunology, Microscopic Polyangiitis, Azathioprine, Churg-Strauss Syndrome, Placebo, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Rheumatology, Recurrence, Internal medicine, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Sinusitis, 10. No inequality, Adverse effect, Glucocorticoids, Aged, Rhinitis, Asthma, 030203 arthritis & rheumatology, business.industry, Polyarteritis nodosa, Remission Induction, Middle Aged, medicine.disease, Polyarteritis Nodosa, 3. Good health, Disease Progression, Drug Therapy, Combination, Female, business, Granulomatosis with polyangiitis, Microscopic polyangiitis, Immunosuppressive Agents, medicine.drug
Abstract

Objective In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). Methods All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. Results Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. Conclusion Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.

Published
2017

42. Characteristics and Management of IgA Vasculitis (Henoch-Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey

Author

Loic Raffray, Noémie Jourde-Chiche, Benjamin Terrier, Julie Goutte, Alice Bérezné, Boris Bienvenu, Marc André, Aurélie Hummel, Jean-François Augusto, Geoffrey Urbanski, Agnès Dechartres, Nathalie Costedoat-Chalumeau, Christian Lavigne, Xavier Puéchal, Elie Zagdoun, Charlotte Girard, Eric Thervet, Bertrand Lioger, Mélanie Roriz, Patrice Cacoub, Arsène Mekinian, Alexandra Audemard-Verger, Stanislas Faguer, Johan Chanal, Guillaume Moulis, A. Baldolli, Noémie Le Gouellec, Nihal Martis, Evangeline Pillebout, Etienne Rivière, Loïc Guillevin, Sébastien Sanges, Zahir Amoura, Alban Deroux, François Maurier, and Mélanie Catroux

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Univariate analysis, Henoch-Schonlein purpura, business.industry, Immunology, Retrospective cohort study, Odds ratio, medicine.disease, Logistic regression, Confidence interval, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, IgA vasculitis, Rheumatology, Internal medicine, Propensity score matching, medicine, Immunology and Allergy, 030212 general & internal medicine, business
Abstract

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models. Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10–12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28–10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29–2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00–3.20; P = 0.049). Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first‐line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.

Published
2017

43. Concordance of Time-of-Flight MRA and Digital Subtraction Angiography in Adult Primary Central Nervous System Vasculitis

Author

H. de Boysson, Christian Pagnoux, Emmanuel Touzé, M. Zuber, Caroline Arquizan, Gregoire Boulouis, Olivier Naggara, Loïc Guillevin, Boris Bienvenu, N. Dequatre, Achille Aouba, Olivier Detante, and Jean-Jacques Parienti

Subjects
Adult, Male, medicine.medical_specialty, Concordance, Magnetic resonance angiography, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Vasculitis, Central Nervous System, Aged, Retrospective Studies, medicine.diagnostic_test, Arterial stenosis, business.industry, Adult Brain, Angiography, Digital Subtraction, Retrospective cohort study, Digital subtraction angiography, Middle Aged, Neurovascular bundle, medicine.disease, eye diseases, body regions, cardiovascular system, Female, Neurology (clinical), Radiology, business, Vasculitis, Magnetic Resonance Angiography, 030217 neurology & neurosurgery, circulatory and respiratory physiology, Cohort study
Abstract

BACKGROUND AND PURPOSE: 3D-TOF-MRA and DSA are 2 available tools to demonstrate neurovascular involvement in primary central nervous system vasculitis. We aimed to compare the diagnostic concordance of vessel imaging using 3D-TOF-MRA and DSA in patients with primary central nervous system vasculitis. MATERIALS AND METHODS: We retrospectively identified all patients included in the French primary central nervous system vasculitis cohort of 85 patients who underwent, at baseline, both intracranial 3D-TOF-MRA and DSA in an interval of no more than 2 weeks and before treatment initiation. Two neuroradiologists independently reviewed all 3D-TOF-MRA and DSA imaging. Brain vasculature was divided into 25 arterial segments. Concordance between 3D-TOF-MRA and DSA for the identification of arterial stenosis was assessed by the Cohen κ Index. RESULTS: Thirty-one patients met the inclusion criteria, including 20 imaged with a 1.5T MR unit and 11 with a 3T MR unit. Among the 25 patients (81%) with abnormal DSA findings, 24 demonstrated abnormal 3D-TOF-MRA findings, whereas all 6 remaining patients with normal DSA findings had normal 3D-TOF-MRA findings. In the per-segment analysis, concordance between 1.5T 3D-TOF-MRA and DSA was 0.82 (95% CI, 0.75–0.93), and between 3T 3D-TOF-MRA and DSA, it was 0.87 (95% CI, 0.78–0.91). CONCLUSIONS: 3D-TOF-MRA shows a high concordance with DSA in diagnostic performance when analyzing brain vasculature in patients with primary central nervous system vasculitis. In patients with negative 3T 3D-TOF-MRA findings, the added diagnostic value of DSA is limited.

Published
2017

44. Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system

Author

Alexis Régent, Hubert de Boysson, Nicolas Gaillard, Christian Pagnoux, Mathieu Zuber, Loïc Guillevin, Caroline Arquizan, Olivier Naggara, Emanuel Touzé, Jean-Jacques Parienti, Achille Aouba, Antoine Néel, Gregoire Boulouis, Boris Bienvenu, and Olivier Detante

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Multivariate analysis, medicine.diagnostic_test, business.industry, Odds ratio, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Maintenance therapy, Modified Rankin Scale, Internal medicine, Immunology, Cohort, Biopsy, medicine, Pharmacology (medical), Vasculitis, business, 030217 neurology & neurosurgery, Glucocorticoid, medicine.drug
Abstract

Objective We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). Methods We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Results Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001]. Conclusion The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings.

Published
2017

45. Treatment of giant-cell arteritis, a literature review

Author

Hubert de Boysson, Bénédicte Watelet, Boris Bienvenu, and Maxime Samson

Subjects
medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Cyclophosphamide, Medication Therapy Management, Giant Cell Arteritis, Osteoporosis, Azathioprine, Disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, medicine, Humans, Arteritis, Intensive care medicine, Glucocorticoids, 030203 arthritis & rheumatology, Tumor Necrosis Factor-alpha, business.industry, medicine.disease, Surgery, Giant cell arteritis, Methotrexate, chemistry, Antirheumatic Agents, Drug Therapy, Combination, business, Vasculitis, 030217 neurology & neurosurgery, medicine.drug
Abstract

Giant-cell arteritis (GCA) is the most common vasculitis in people aged more than 50 years. Despite the frequency of this disease, there is currently no international consensus on its therapeutic modalities. The aim of this study was to conduct a review on an international literature about the treatment of GCA, whatever the clinical pattern might be. Oral corticosteroids remain the cornerstone treatment, possibly preceded by intravenous bolus in complicated forms. In cases of glucocorticoid (GC) dependence or GC-related side effects, a GC-sparing agent may be necessary. Methotrexate is one of the most used treatments despite its low level of evidence and mild efficacy. Cyclophosphamide and tocilizumab look promising but require validation in further studies. The results for TNF-α blockers and azathioprine are disappointing. Preventing complications of prolonged corticosteroid therapy is a world challenge and the management of GC-induced osteoporosis is not the same from one country to another. There is a significant risk of arterial thrombosis, mainly at treatment onset, which may encourage to associate an antiplatelet therapy, especially in patients with other cardiovascular risk factors. Place of statins in the treatment of the disease is uncertain.

Published
2017

47. Efficacité et bonne tolérance du rituximab sur un purpura thrombopénique immunologique chronique révélant un syndrome de délétion 22q11

Author

M. Gerard, Boris Bienvenu, Achille Aouba, Mathieu Vautier, Olivier Hermine, Sophie Georgin-Lavialle, and E. Lacaze

Subjects
Gynecology, medicine.medical_specialty, business.industry, Treatment outcome, Gastroenterology, 030204 cardiovascular system & hematology, Auto immunite, 03 medical and health sciences, 0302 clinical medicine, 22q11 Deletion Syndrome, 030220 oncology & carcinogenesis, Internal Medicine, medicine, Rituximab, 22q11 deletion, business, medicine.drug
Abstract

Resume Introduction La microdeletion 22q11 est une affection genetique associant un syndrome poly-malformatif et une dysimmunite. L’association de manifestations auto-immunes au deficit immunitaire constitue l’enjeu therapeutique de cette affection. Observation Nous rapportons l’observation d’un patient de 28 ans consultant pour des manifestations hemorragiques revelant une thrombocytopenie (numeration plaquettaire : 15 000/mm3) de mecanisme mixte, immunologique et central. Les antecedents du patient, l’existence d’un syndrome malformatif cardio-facial, d’une hypoparathyroidie et d’un deficit immunitaire modere conduisaient au diagnostic moleculaire de syndrome de deletion 22q11. Apres echec des immunoglobulines polyvalentes, un traitement par rituximab seul permettait une re-ascension du taux de plaquettes a ses valeurs usuelles de 100–120 000/mm3 en 4 semaines et une remission complete du tableau hemorragique sans complication infectieuse associee apres 4 ans de suivi. Conclusion Le rituximab peut etre une alternative therapeutique a la corticotherapie au cours des manifestations auto-immunes associees aux formes moderees de syndrome 22q11, sans en aggraver le deficit immunitaire.

Published
2016

48. Évaluation médico-économique d’une stratégie standardisée pour le diagnostic étiologique des uvéites : résultats de l’étude ULISSE

Author

Pascal Sève, A. De Parisot, Grégory Pugnet, Sophie Rivière, Boris Bienvenu, L. Kodjikian, Neila Sedira, Philip Bielefeld, M. André, Nathalie Tieulie, Bahram Bodaghi, Yvan Jamilloux, Emmanuel Héron, Pascal Cathébras, P. Guerre, Ulisse, and S. David

Subjects
Gastroenterology, Internal Medicine
Abstract

Introduction L’objectif de cette etude etait d’evaluer de maniere prospective les consequences financieres d’une approche diagnostique standardisee par rapport a une strategie ouverte pour le diagnostic etiologique des uveites. Patients et methodes L’etude ULISSE (PHRC 2009) etait un essai comparatif randomise, de non-inferiorite, prospectif et multicentrique. Les patients consecutifs atteints d’uveite, suivis ou consultant dans l’un des departements d’ophtalmologie des centres participants, ont ete inclus. Dans le groupe standardise, tous les patients presentaient un bilan minimal, quel que soit le type d’uveite (numeration globulaire complete, taux de sedimentation erythrocytaire, proteine C reactive, test cutane a la tuberculine, serologie de la syphilis et radiographie pulmonaire), suivis d’investigations complementaires plus complexes en fonction des constatations ophtalmologiques (type anatomique, lateralite, caractere granulomateux, evolution, presence de signes specifiques). Dans le groupe ouvert, l’ophtalmologiste pouvait ordonner n’importe quel type d’examens complementaires. Le resultat principal etait le cout moyen par patient de chaque strategie. Resultats Neuf cent trois patients ont ete inclus entre janvier 2010 et mai 2013. Le cout moyen par patient de la strategie standardisee etait de 182,97 euros [IC95 % (173,14 ; 192,80)] et le cout moyen par patient de la strategie ouverte etait de 251,75 euros [IC95 % (229,24 ; 274,25)]. Par consequent, le cout moyen par patient de la strategie standardisee etait significativement inferieur au cout moyen par patient de la strategie ouverte (p Conclusion La strategie standardisee, bien que non-inferieure a la strategie ouverte en termes de rentabilite diagnostique, permet des economies significatives pour le diagnostic etiologique des uveites.

Published
2019

50. Effectiveness and tolerance of off-label use of tocilizumab in autoimmune diseases: A Multicenter Study

Author

Geoffrey Urbanski, Laurent Chiche, Boris Bienvenu, Martin Michaud, and Olivier Lidove

Subjects
Adult-onset Still's disease, medicine.medical_specialty, business.industry, Off-Label Use, Off-label use, medicine.disease, Antibodies, Monoclonal, Humanized, Autoimmune Diseases, Polymyalgia rheumatica, chemistry.chemical_compound, Tocilizumab, Rheumatology, chemistry, Multicenter study, Internal medicine, medicine, Humans, business
Published
2019

Catalog

Books, media, physical & digital resources
See catalog results