1. Tapering Canakinumab Monotherapy in Patients with Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results from an Open‐label, Randomized Phase IIIb/IV Study
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Quartier, P, Alexeeva, E, Tamàs, C, Chasnyk, V, Wulffraat, N, Palmblad, K, Wouters, C, Brunner, H, Marzan, K, Schneider, R, Horneff, G, Martini, A, Anton, J, Wei, X, Slade, A, Ruperto, N, Abrams, K, Emminger, W, Ulbrich, A, Fodor, S, Desomer, L, Lauwerys, B, Brichard, B, Boulanger, C, Levy, G, Goffin, L, Quoc Le, P, Bandeira, M, Feitosa Pelajo, C, Knupp Feitosa, S, Costa, C, Cristine Felix Rodrigues, M, Artur Almeida da Silva, C, Maria Mattei de, L, Kozu, K, Laxer, R, Houghton, K, Tucker, L, Morishita, K, Mogenet, A, Mouy, R, Bader Meunier, B, Meyzer, C, Semeraro, M, Ben‐brahim, O, Kone‐paut, I, Galeotti, C, Rossi, L, Dusser, P, Cherquaoui, B, Belot, A, Duquesne, A, Caroline, F, Audrey, L, Desjonqueres, M, Foeldvari, I, Kienast, A, Willig, B, Barthel, D, Peitz, J, Wintrich, S, Felix Geikowski, T, Carina Schulz, A, Hufnagel, M, Hirdes, M, Kubicki, R, Kirschner, J, Janda, A, Jacob, A, Emerich, C, Raab, A, Ngoumou, G, Minden, K, Lieber, M, von Stuckrad, S, Kuemmerle Deschner, J, Hansmann, S, Schleich, T, Maria Magunia, I, Riethmuller, J, Anders, N, Lehmann, H, de Laffolie, J, Lutz, T, Grulich‐henn, J, Pfeil, J, Helling‐bakki, A, Trauzeddel, R, Haselbusch, D, Kolbeck, H, Weissbarth‐riedel, E, Froehlich, A, Ponyi, A, Garan, D, Orban, I, Sevcic, K, Butbul, Y, Brik, R, Hashkes, P, Toker, O, Haviv, R, Uziel, Y, Moshe, V, Rothschild, M, Harel, L, Amarilyo, G, Tal, R, Hamad Said, M, Tirosh, I, Spielman, S, Gerstein, M, Ravelli, A, Schiappapietra, B, Camilla Varnier, G, Finetti, M, Marasini, M, Caorsi, R, Rosina, S, Federici, S, Pontikaki, I, Luigi Meroni, P, Gerloni, V, Ughi, N, Ubiali, T, Alessio, M, Della Casa, R, Jozef Vastert, S, Frans Swart, J, van Royen‐Kerhof, A, Schatorje, E, Van Iperen‐Schutte, G, Rutkowska‐sak, L, Szczygielska, I, Kwiatkowska, M, Marusak‐banacka, M, Gietka, P, Isaeva, K, Denisova, R, Snegireva, L, Dubko, M, Kostik, M, Buchinskaia, N, Kalashnikova, O, Avrusin, S, Masalova, V, Nunez Cuadros, E, Diez, G, Galindo Zavala, R, Bou Torrent, R, Iglesias, E, Calzada, J, Bittermann, V, Lucica Boteanu, A, Luz Gamir, M, Calvo, I, Lopez, B, Gonzalez, I, Fernandez, L, Clemente Garulo, D, Carlos Lopez Robledillo, J, Merino, R, Alcobendas, R, Remesal, A, Murias, S, Magnusson, B, Kasapcopur, O, Barut, K, Adrovic, A, Sahin, S, Erguven, M, Gozdenur Savci, R, Ozen, S, Demir, S, Bilginer, Y, Serap Avci, Z, Deriz Batu, E, Reiff, A, Ramanatham, A, Brown, D, Shaham, B, Parks, S, Cidon, M, Higgins, G, Spencer, C, Rossette, J, Jones, K, Bout Tabaku, S, Farley, S, Akoghlanian, S, Pierre Quartier, Ekaterina Alexeeva, Constantin Tamàs, Vyacheslav Chasnyk, Nico Wulffraat, Karin Palmblad, Carine Wouters, Hermine Brunner, Katherine Marzan, Rayfel Schneider, Gerd Horneff, Alberto Martini, Jordi Anton, Xiaoling Wei, Alan Slade, Nicolino Ruperto, Ken Abrams, Wolfgang Emminger, Andrea Ulbrich, Sugarka Fodor, Lien Desomer, Bernard Lauwerys, Bénédicte Brichard, Cécile Boulanger, Gabriel Levy, Laurence Goffin, Phu Quoc Le, Marcia Bandeira, Christina Feitosa Pelajo, Sheila Knupp Feitosa, Christianne Costa, Marta Cristine Felix Rodrigues, Clovis Artur Almeida da Silva, Lucia Maria Mattei de, Katia Kozu, Ronald Laxer, Kristin Houghton, Lori Tucker, Kimberly Morishita, Agnes Mogenet, Richard Mouy, Brigitte Bader Meunier, Candice Meyzer, Michaela Semeraro, Ouafa Ben‐Brahim, Isabelle Kone‐Paut, Caroline Galeotti, Linda Rossi, Perrine Dusser, Bilade Cherquaoui, Alexandre Belot, Agnes Duquesne, Freychet Caroline, Laurent Audrey, Marine Desjonqueres, Ivan Foeldvari, Antonia Kienast, Barbara Willig, Deborah Barthel, Joachim Peitz, Stefanie Wintrich, Tilman Felix Geikowski, Anna Carina Schulz, Markus Hufnagel, Marc Hirdes, Rouven Kubicki, Janbernd Kirschner, Ales Janda, Andre Jacob, Cornelia Emerich, Anna Raab, Gonza Ngoumou, Kirsten Minden, Mareike Lieber, Sae‐Lim von Stuckrad, Jasmin Kuemmerle Deschner, Sandra Hansmann, Tom Schleich, Ines Maria Magunia, Joachim Riethmuller, Nicole Anders, Hartwig Lehmann, Jan de Laffolie, Thomas Lutz, Juergen Grulich‐Henn, Johannes Pfeil, Astrid Helling‐Bakki, Ralf Trauzeddel, Daniel Haselbusch, Henryk Kolbeck, Elisabeth Weissbarth‐Riedel, Anja Froehlich, Andrea Ponyi, Diana Garan, Ilonka Orban, Krisztina Sevcic, Yonatan Butbul, Riva Brik, Philip Hashkes, Ori Toker, Ruby Haviv, Yosef Uziel, Rubi Haviv, Veronica Moshe, Michal Rothschild, Liora Harel, Gil Amarilyo, Rotem Tal, Mohamad Hamad Said, Irit Tirosh, Shiri Spielman, Maya Gerstein, Angelo Ravelli, Benedetta Schiappapietra, Giulia Camilla Varnier, Martina Finetti, Maurizio Marasini, Roberta Caorsi, Silvia Rosina, Silvia Federici, Irene Pontikaki, Pier Luigi Meroni, Valeri Gerloni, Nicola Ughi, Tania Ubiali, Maria Alessio, Roberto Della Casa, Sebastiaan Jozef Vastert, Joost Frans Swart, A. van Royen‐Kerhof, Ellen Schatorje, G. Van Iperen‐Schutte, Lidia Rutkowska‐Sak, Izabela Szczygielska, Malgorzata Kwiatkowska, Maria Marusak‐Banacka, Piotr Gietka, Kseniya Isaeva, Rina Denisova, Ludmila Snegireva, Margarita Dubko, Mikhail Kostik, Natalia Buchinskaia, Olga Kalashnikova, Sergey Avrusin, Vera Masalova, Esmeralda Nunez Cuadros, Gisela Diez, Rocio Galindo Zavala, Rosa Bou Torrent, Estibaliz Iglesias, Joan Calzada, Violeta Bittermann, Alina Lucica Boteanu, Maria Luz Gamir, Inmaculada Calvo, Berta Lopez, Isabel Gonzalez, Laura Fernandez, Daniel Clemente Garulo, Juan Carlos Lopez Robledillo, Rosa Merino, Rosa Alcobendas, Agustin Remesal, Sara Murias, Bo Magnusson, Ozgur Kasapcopur, Kenan Barut, Amra Adrovic, Sezgin Sahin, Muferet Erguven, Refia Gozdenur Savci, Seza Ozen, Selcan Demir, Yelda Bilginer, Zehra Serap Avci, Ezgi Deriz Batu, Andreas Reiff, Anusha Ramanatham, Diana Brown, Bracha Shaham, Shirley Parks, Michal Cidon, Gloria Higgins, Charles Spencer, Jenny Rossette, Karla Jones, Sharon Bout Tabaku, Shelli Farley, Shoghik Akoghlanian, Quartier, P, Alexeeva, E, Tamàs, C, Chasnyk, V, Wulffraat, N, Palmblad, K, Wouters, C, Brunner, H, Marzan, K, Schneider, R, Horneff, G, Martini, A, Anton, J, Wei, X, Slade, A, Ruperto, N, Abrams, K, Emminger, W, Ulbrich, A, Fodor, S, Desomer, L, Lauwerys, B, Brichard, B, Boulanger, C, Levy, G, Goffin, L, Quoc Le, P, Bandeira, M, Feitosa Pelajo, C, Knupp Feitosa, S, Costa, C, Cristine Felix Rodrigues, M, Artur Almeida da Silva, C, Maria Mattei de, L, Kozu, K, Laxer, R, Houghton, K, Tucker, L, Morishita, K, Mogenet, A, Mouy, R, Bader Meunier, B, Meyzer, C, Semeraro, M, Ben‐brahim, O, Kone‐paut, I, Galeotti, C, Rossi, L, Dusser, P, Cherquaoui, B, Belot, A, Duquesne, A, Caroline, F, Audrey, L, Desjonqueres, M, Foeldvari, I, Kienast, A, Willig, B, Barthel, D, Peitz, J, Wintrich, S, Felix Geikowski, T, Carina Schulz, A, Hufnagel, M, Hirdes, M, Kubicki, R, Kirschner, J, Janda, A, Jacob, A, Emerich, C, Raab, A, Ngoumou, G, Minden, K, Lieber, M, von Stuckrad, S, Kuemmerle Deschner, J, Hansmann, S, Schleich, T, Maria Magunia, I, Riethmuller, J, Anders, N, Lehmann, H, de Laffolie, J, Lutz, T, Grulich‐henn, J, Pfeil, J, Helling‐bakki, A, Trauzeddel, R, Haselbusch, D, Kolbeck, H, Weissbarth‐riedel, E, Froehlich, A, Ponyi, A, Garan, D, Orban, I, Sevcic, K, Butbul, Y, Brik, R, Hashkes, P, Toker, O, Haviv, R, Uziel, Y, Moshe, V, Rothschild, M, Harel, L, Amarilyo, G, Tal, R, Hamad Said, M, Tirosh, I, Spielman, S, Gerstein, M, Ravelli, A, Schiappapietra, B, Camilla Varnier, G, Finetti, M, Marasini, M, Caorsi, R, Rosina, S, Federici, S, Pontikaki, I, Luigi Meroni, P, Gerloni, V, Ughi, N, Ubiali, T, Alessio, M, Della Casa, R, Jozef Vastert, S, Frans Swart, J, van Royen‐Kerhof, A, Schatorje, E, Van Iperen‐Schutte, G, Rutkowska‐sak, L, Szczygielska, I, Kwiatkowska, M, Marusak‐banacka, M, Gietka, P, Isaeva, K, Denisova, R, Snegireva, L, Dubko, M, Kostik, M, Buchinskaia, N, Kalashnikova, O, Avrusin, S, Masalova, V, Nunez Cuadros, E, Diez, G, Galindo Zavala, R, Bou Torrent, R, Iglesias, E, Calzada, J, Bittermann, V, Lucica Boteanu, A, Luz Gamir, M, Calvo, I, Lopez, B, Gonzalez, I, Fernandez, L, Clemente Garulo, D, Carlos Lopez Robledillo, J, Merino, R, Alcobendas, R, Remesal, A, Murias, S, Magnusson, B, Kasapcopur, O, Barut, K, Adrovic, A, Sahin, S, Erguven, M, Gozdenur Savci, R, Ozen, S, Demir, S, Bilginer, Y, Serap Avci, Z, Deriz Batu, E, Reiff, A, Ramanatham, A, Brown, D, Shaham, B, Parks, S, Cidon, M, Higgins, G, Spencer, C, Rossette, J, Jones, K, Bout Tabaku, S, Farley, S, Akoghlanian, S, Pierre Quartier, Ekaterina Alexeeva, Constantin Tamàs, Vyacheslav Chasnyk, Nico Wulffraat, Karin Palmblad, Carine Wouters, Hermine Brunner, Katherine Marzan, Rayfel Schneider, Gerd Horneff, Alberto Martini, Jordi Anton, Xiaoling Wei, Alan Slade, Nicolino Ruperto, Ken Abrams, Wolfgang Emminger, Andrea Ulbrich, Sugarka Fodor, Lien Desomer, Bernard Lauwerys, Bénédicte Brichard, Cécile Boulanger, Gabriel Levy, Laurence Goffin, Phu Quoc Le, Marcia Bandeira, Christina Feitosa Pelajo, Sheila Knupp Feitosa, Christianne Costa, Marta Cristine Felix Rodrigues, Clovis Artur Almeida da Silva, Lucia Maria Mattei de, Katia Kozu, Ronald Laxer, Kristin Houghton, Lori Tucker, Kimberly Morishita, Agnes Mogenet, Richard Mouy, Brigitte Bader Meunier, Candice Meyzer, Michaela Semeraro, Ouafa Ben‐Brahim, Isabelle Kone‐Paut, Caroline Galeotti, Linda Rossi, Perrine Dusser, Bilade Cherquaoui, Alexandre Belot, Agnes Duquesne, Freychet Caroline, Laurent Audrey, Marine Desjonqueres, Ivan Foeldvari, Antonia Kienast, Barbara Willig, Deborah Barthel, Joachim Peitz, Stefanie Wintrich, Tilman Felix Geikowski, Anna Carina Schulz, Markus Hufnagel, Marc Hirdes, Rouven Kubicki, Janbernd Kirschner, Ales Janda, Andre Jacob, Cornelia Emerich, Anna Raab, Gonza Ngoumou, Kirsten Minden, Mareike Lieber, Sae‐Lim von Stuckrad, Jasmin Kuemmerle Deschner, Sandra Hansmann, Tom Schleich, Ines Maria Magunia, Joachim Riethmuller, Nicole Anders, Hartwig Lehmann, Jan de Laffolie, Thomas Lutz, Juergen Grulich‐Henn, Johannes Pfeil, Astrid Helling‐Bakki, Ralf Trauzeddel, Daniel Haselbusch, Henryk Kolbeck, Elisabeth Weissbarth‐Riedel, Anja Froehlich, Andrea Ponyi, Diana Garan, Ilonka Orban, Krisztina Sevcic, Yonatan Butbul, Riva Brik, Philip Hashkes, Ori Toker, Ruby Haviv, Yosef Uziel, Rubi Haviv, Veronica Moshe, Michal Rothschild, Liora Harel, Gil Amarilyo, Rotem Tal, Mohamad Hamad Said, Irit Tirosh, Shiri Spielman, Maya Gerstein, Angelo Ravelli, Benedetta Schiappapietra, Giulia Camilla Varnier, Martina Finetti, Maurizio Marasini, Roberta Caorsi, Silvia Rosina, Silvia Federici, Irene Pontikaki, Pier Luigi Meroni, Valeri Gerloni, Nicola Ughi, Tania Ubiali, Maria Alessio, Roberto Della Casa, Sebastiaan Jozef Vastert, Joost Frans Swart, A. van Royen‐Kerhof, Ellen Schatorje, G. Van Iperen‐Schutte, Lidia Rutkowska‐Sak, Izabela Szczygielska, Malgorzata Kwiatkowska, Maria Marusak‐Banacka, Piotr Gietka, Kseniya Isaeva, Rina Denisova, Ludmila Snegireva, Margarita Dubko, Mikhail Kostik, Natalia Buchinskaia, Olga Kalashnikova, Sergey Avrusin, Vera Masalova, Esmeralda Nunez Cuadros, Gisela Diez, Rocio Galindo Zavala, Rosa Bou Torrent, Estibaliz Iglesias, Joan Calzada, Violeta Bittermann, Alina Lucica Boteanu, Maria Luz Gamir, Inmaculada Calvo, Berta Lopez, Isabel Gonzalez, Laura Fernandez, Daniel Clemente Garulo, Juan Carlos Lopez Robledillo, Rosa Merino, Rosa Alcobendas, Agustin Remesal, Sara Murias, Bo Magnusson, Ozgur Kasapcopur, Kenan Barut, Amra Adrovic, Sezgin Sahin, Muferet Erguven, Refia Gozdenur Savci, Seza Ozen, Selcan Demir, Yelda Bilginer, Zehra Serap Avci, Ezgi Deriz Batu, Andreas Reiff, Anusha Ramanatham, Diana Brown, Bracha Shaham, Shirley Parks, Michal Cidon, Gloria Higgins, Charles Spencer, Jenny Rossette, Karla Jones, Sharon Bout Tabaku, Shelli Farley, and Shoghik Akoghlanian
- Abstract
Objective: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA). Methods: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study. Results: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified. Conclusion: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consisten
- Published
- 2021