Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)
Peter Collins, Francesco Baudo, Paul Knoebl, Hervé Lévesque, László Nemes, Fabio Pellegrini, Pascual Marco, Lilian Tengborn, Angela Huth-Kühne, EACH2 registry collaborators, Gerold Aspoeck, Max Heistinger, Paul Knöbl, Anne Makipernaa, Hélène André, Achille Aouba, Sylvia Bellucci, Philippe Beurrier, Jeanne Yvonne Borg, Luc Darnige, Jean Devignes, Roseline d'Oiron, Philippe Gautier, Valérie Gay, Stéphane Girault, Yves Gruel, Viviane Guerin, Nathalie Hézard, Mehdi Khellaf, Martial Koenig, Hervé Lévesque, François Lifermann, Raphael Marlu, Jacques Ninet, Jocelyne Peynet, Thomas Quéméneur, Chantal Rothschild, Nicolas Schleinitz, Marianne Sigaud, Sébastien Trouillier, Sophie Voisin, Andreas Giebl, Katharina Holstein, Angela Huth-Kühne, Ralph M Loreth, Udo Steigerwald, Andreas Tiede, George Theodossiades, László Nemes, Gaspar Radvanyi, Agota Schlammadinger, Giovanni Barillari, Samantha Pasca, Francesco Baudo, Teresa Caimi, Laura Contino, Crippa Luciano D'Angelo Armando, Annalisa Fattorini, Giovanni Di Minno, Anna Maria Cerbone, Dario Di Minno, Marco D'incà, Anna Falanga, Anna Maggioni, Teresa Lerede, Massimo Franchini, Gianluca Gaidano, Lorenzo De Paoli, Gabriella Gamba, Raffaele Ghirardi, Mauro Girotto, Delios Tasca, Elvira Grandone, Giovanni Tiscia, Davide Imberti, Alfonso Iorio, Raffaele Landolfi, Leonardo Di Gennaro, Linda Novarese, Guglielmo Mariani, Mario Lapecorella, Marco Marietta, Paola Pedrazzi, Maria Gabriella Mazzucconi, Cristina Santoro, Massimo Morfini, Silvia Linari, Stefano Moratelli, Rossella Paolini, Gavino Piseddu, Renzo Poggio, Enrico Pogliani, Monica Carpenedo, Chiara Remiddi, Elena Santagostino, Maria Elisa Mancuso, Rita Santoro, Giuseppina Papaleo, Piercarla Schinco, Alessandra Borchiellini, Federica Valeri, Anna Rita Scortechini, Sergio Siragusa, Gianluca Sottilotta, Alessandro Squizzato, Giuseppe Tagariello, Roberto Sartori, Anna Rita Tagliaferri, Caterina Di Perna, Gianna Franca Rivolta, Sophie Testa, Oriana Paoletti, Vincenzo Toschi, Ezio Zanon, Barbara Brandolin, Karly Hamulyák, Pieter Kamphuisen, Britta Laros-van Gorkom, Frank W G Leebeek, Nijziel Marten, Irena Novakova, Roger Schutgens, P W G van der Linden, Joost van Esser, J van der Meer, Paula Ypma, Manuel Campos, Carlos Aguilar, Carmen Altisent, Nuria Bermejo, Raquel Del Campo, María Ferreiro Argüelles, Rosario González Boullosa, María José Gutiérrez Pimentel, Victor Jiménez-Yuste, Lucia Jose-Felix, Pascual Marco, Maria Eva Mingot, Rosario Perez Garrido, Noelia Z Perez Gonzale, Manuel Prieto Garcia, Ana María Rodriguez-Huerta, Carmen Sedano, Alexandra Tolosa Munoz, Fariba Baghaei, Lilian Tengborn, Françoise Boehlen, Wolfgang Korte, Pratima Chowdary, Peter Collins, Gillian Evans, Suzanne Pavord, Savita Rangarajan, Jonathan Wilde, Peter Collins, Francesco Baudo, Paul Knoebl, Hervé Lévesque, László Nemes, Fabio Pellegrini, Pascual Marco, Lilian Tengborn, Angela Huth-Kühne, EACH2 registry collaborators, Gerold Aspoeck, Max Heistinger, Paul Knöbl, Anne Makipernaa, Hélène André, Achille Aouba, Sylvia Bellucci, Philippe Beurrier, Jeanne Yvonne Borg, Luc Darnige, Jean Devignes, Roseline d'Oiron, Philippe Gautier, Valérie Gay, Stéphane Girault, Yves Gruel, Viviane Guerin, Nathalie Hézard, Mehdi Khellaf, Martial Koenig, Hervé Lévesque, François Lifermann, Raphael Marlu, Jacques Ninet, Jocelyne Peynet, Thomas Quéméneur, Chantal Rothschild, Nicolas Schleinitz, Marianne Sigaud, Sébastien Trouillier, Sophie Voisin, Andreas Giebl, Katharina Holstein, Angela Huth-Kühne, Ralph M Loreth, Udo Steigerwald, Andreas Tiede, George Theodossiades, László Nemes, Gaspar Radvanyi, Agota Schlammadinger, Giovanni Barillari, Samantha Pasca, Francesco Baudo, Teresa Caimi, Laura Contino, Crippa Luciano D'Angelo Armando, Annalisa Fattorini, Giovanni Di Minno, Anna Maria Cerbone, Dario Di Minno, Marco D'incà, Anna Falanga, Anna Maggioni, Teresa Lerede, Massimo Franchini, Gianluca Gaidano, Lorenzo De Paoli, Gabriella Gamba, Raffaele Ghirardi, Mauro Girotto, Delios Tasca, Elvira Grandone, Giovanni Tiscia, Davide Imberti, Alfonso Iorio, Raffaele Landolfi, Leonardo Di Gennaro, Linda Novarese, Guglielmo Mariani, Mario Lapecorella, Marco Marietta, Paola Pedrazzi, Maria Gabriella Mazzucconi, Cristina Santoro, Massimo Morfini, Silvia Linari, Stefano Moratelli, Rossella Paolini, Gavino Piseddu, Renzo Poggio, Enrico Pogliani, Monica Carpenedo, Chiara Remiddi, Elena Santagostino, Maria Elisa Mancuso, Rita Santoro, Giuseppina Papaleo, Piercarla Schinco, Alessandra Borchiellini, Federica Valeri, Anna Rita Scortechini, Sergio Siragusa, Gianluca Sottilotta, Alessandro Squizzato, Giuseppe Tagariello, Roberto Sartori, Anna Rita Tagliaferri, Caterina Di Perna, Gianna Franca Rivolta, Sophie Testa, Oriana Paoletti, Vincenzo Toschi, Ezio Zanon, Barbara Brandolin, Karly Hamulyák, Pieter Kamphuisen, Britta Laros-van Gorkom, Frank W G Leebeek, Nijziel Marten, Irena Novakova, Roger Schutgens, P W G van der Linden, Joost van Esser, J van der Meer, Paula Ypma, Manuel Campos, Carlos Aguilar, Carmen Altisent, Nuria Bermejo, Raquel Del Campo, María Ferreiro Argüelles, Rosario González Boullosa, María José Gutiérrez Pimentel, Victor Jiménez-Yuste, Lucia Jose-Felix, Pascual Marco, Maria Eva Mingot, Rosario Perez Garrido, Noelia Z Perez Gonzale, Manuel Prieto Garcia, Ana María Rodriguez-Huerta, Carmen Sedano, Alexandra Tolosa Munoz, Fariba Baghaei, Lilian Tengborn, Françoise Boehlen, Wolfgang Korte, Pratima Chowdary, Peter Collins, Gillian Evans, Suzanne Pavord, Savita Rangarajan, Jonathan Wilde
Abstract
Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.
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Source: PubMed