IRIS

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).

Ofatumumab versus Teriflunomide in Multiple Sclerosis / Hauser, S. L.; Bar-Or, A.; Cohen, J. A.; Comi, G.; Correale, J.; Coyle, P. K.; Cross, A. H.; de Seze, J.; Leppert, D.; Montalban, X.; Selmaj, K.; Wiendl, H.; Kerloeguen, C.; Willi, R.; Li, B.; Kakarieka, A.; Tomic, D.; Goodyear, A.; Pingili, R.; Haring, D. A.; Ramanathan, K.; Merschhemke, M.; Kappos, L.; Stephen, L Hauser; Kappos, Ludwig; Bar-Or, Amit; Jeffrey, A Cohen; Comi, Giancarlo; Correale, Jorge; Patricia, K Coyle; Cross, Anne; Jerome de Seze, ; Montalban, Xavier; Selmaj, Krzysztof; Wiendl, Heinz; Stephen, C Reingold; Garry, R Cutter; Doerner, Thomas; Hartung, Hans-Peter; Per Soelberg Sørensen, ; Steiner, Israel; Jerry, S Wolinsky; Ballario, Carlos; Christian Calvo Vildoso, ; Jorge Gustavo Jose, ; Norma Haydee Deri, ; Liwacki, Susana; Lechner-Scott, Jeannette; Parratt, John; Hodgkinson, Suzanne; Maida, Eva-Maria; Leutmezer, Fritz; Willekens, Barbara; Bart Van Wijmeersch, ; Laureys, Guy; Caekebeke, Jo; Geens, Karine; Vanopdenbosch, Ludo; Deryck, Olivier; Delvaux, Valerie; Vincent Van Pesch, ; Milanov, Ivan; Tarnev, Ivaylo; Haralanov, Lyubomir; Maria Manova Slavova, ; Shotekov, Penko; Emond, Francois; Grandmaison, Francois; Jacques, Francois; Lee, Liesly; Marie Sarah Gagne Brosseau, ; Freedman, Mark; Cloutier, Martin; Carruthers, Robert; Morrow, Sarah; Lapierre, Yves; Vladic, Anton; Bokun, Hana; Antoncic, Igor; Marija Bosnjak Pasic, ; Habek, Mario; Silva Butkovic Soldo, ; Vuletic, Vladimira; Martinkova, Alena; Meluzinova, Eva; Stetkarova, Ivana; Mares, Jan; Markova, Jolana; Vachova, Marta; Valis, Martin; Tyblova, Michaela; Dufek, Michal; Skoda, Ondrej; Hradilek, Pavel; Ana Voldsgaard Jensen, ; Helle Hvilsted Nielsen, ; Svendsen, Kristina; Ravnborg, Mads; Peter Vestergaard Rasmussen, ; Gross-Paju, Katrin; Haldre, Sulev; Juha Pekka Eralinna, ; Sumelahti, Marja-Liisa; Brochet, Bruno; Louapre, Celine; Lebrun-Frenay, Christine; David Axel Laplaud, ; Edan, Gilles; Castelnovo, Giovanni; Debouverie, Marc; Vermersch, Patrick; Clavelou, Pierre; Labauge, Pierre; Berthele, Achim; Haghikia, Aiden; Kornhuber, Anselm; Bergmann, Arnfin; Frank, Benedikt; Elias-Hamp, Birte; Tackenberg, Bjoern; Wildemann, Brigitte; Strauss, Erik; Schlegel, Eugen; Florian Then Bergh, ; Nelles, Gereon; Tumani, Hayrettin; Sigel, Karl-Otto; Stangel, Martin; Boehringer, Matthias; Olaf Martin Hoffmann, ; Oschmann, Patrick; Hohlfeld, Reinhard; Walter, Silke; Menck, Sylvia; Sprenger, Till; Ziemssen, Tjalf; Veit Ulrich Becker, ; Straeten, Vera; Kilidireas, Konstantinos; Voumvourakis, Konstantinos; Fakas, Nikolaos; Grigoriadis, Nikolaos; Koves, Agnes; Rozsa, Csilla; Kovacs, Krisztina; Vecsei, Laszlo; Maria, Satori; Biro, Zita; Rohatgi, Anshu; Khurana, Dheeraj; Jeyaraj Durai Pandian, ; Joy Dev Mukherji, ; Pandit, Lekha; Meena Angamuthu Kanikannan, ; Ghosh, Pahari; Chakor, Rahul; Kulkarni, Rahul; Gursahani, Roopkumar; Ravat, Sangeeta; Rangasetty, Srinivasa; Kumar, Suresh; Shifrin, Alla; Karni, Arnon; Shahien, Radi; Milo, Ron; Uccelli, Antonio; Pozzilli, Carlo; Sacca, Francesco; Lus, Giacomo; Girolama Alessandra Marfia, ; Brambilla, Laura; Salvetti, Marco; Filippi, Massimo; Zaffaroni, Mauro; Gallo, Paolo; Rossi, Silvia; Bonavita, Simona; Studer, Valeria; Millers, Andrejs; Karelis, Guntis; Kalnina, Jolanta; Mickeviciene, Dalia; Kizlaitiene, Rasa; Angelica Carbajal Ramirez, ; Juan Jose Lopez Prieto, ; Wokke, Beatrijs; Bob, W Van Oosten; Peter Van Domburg, ; Hupperts, Raymond; Rogier, Q Hintzen; Edland, Astrid; Castaneda, Cesar; Perez, Julio; Gavidia, Martin; Wiak, Andrzej; Karaszewski, Bartosz; Jasinska, Elzbieta; Halina Bartosik Psujek, ; Jastrzebska, Iwona; Slawek, Jaroslaw; Maciejowski, Maciej; Dziki, Miroslaw; Monika Adamczyk Sowa, ; Bonek, Robert; Fryze, Waldemar; Ana Martins Da Silva, ; Timoteo, Angela; Antonio Vasco Salgado, ; Capela, Carlos; Veira, Carlos; Correia, Filipe; Cerqueira, Joao; Joao De Sa, ; Livia De Sousa, ; Gouveia, Raquel; Alina Sergeevna Agafina, ; Anna Naumovna Belova, ; Denis Viktorovich Sazonov, ; Pokhabov, Dmitry; Ekaterina Igorevna Kairbekova, ; Elena Gennadievna Arefieva, ; Farit Axatovich Khabirov, ; Igor Vyacheslavovich Litvinenko, ; Stolyarov, Igor; Irina Aleksandrovna Sokolova, ; Larisa Ivanovna Volkova, ; Maria Vafaevna Davydovskaya, ; Maria Nikolaevna Zaharova, ; Nadezhda Alekseevna Malkova, ; Natalia Agafonovna Totolyan, ; Nikolay Vasilievich Dorogov, ; Stella Anatolievna Sivertseva, ; Kurca, Egon; Krastev, Georgi; Brozman, Miroslav; Koleda, Peter; Turcani, Peter; Valkovic, Peter; Hancinova, Viera; Donath, Vladimir; Retief, Chris; Isaacs, Michael; Albert Saiz Hinarejos, ; Alfredo Rodriguez Antigüedad, ; Bonaventura Casanova Estruch, ; Oreja-Guevara, Celia; Gemma Reig Rosello, ; Jose Carlos Alvarez Cermeño, ; Jose Martinez Rodriguez, ; Jose Meca Lallana, ; Juan Antonio Garcia Merino, ; Lucia Forero Diaz, ; Lucienne Costa Frossard Franca, ; Luis Querol Gutierrez, ; Lluis Ramio Torrenta, ; Pedro Serrano Castro, ; Rafael Arroyo Gonzalez, ; Sara Eichau Madueño, ; Sergio Martinez Yelamos, ; Tamara Castillo Trivino, ; Virgina Meca Lallana, ; Xaviere Montalban Gairin, ; Piehl, Fredrik; Lycke, Jan; Zecca, Chiara; Derfuss, Tobias; Lin, Thy-Sheng; Tiamkao, Somsak; Ayse Nur Yuceyar, ; Soysal, Aysun; Belgin Petek Balci, ; Boz, Cavit; Efendi, Husnu; Terzi, Murat; Sevim, Serhan; Ozakbas, Serkan; Gale, Andrew; Turner, Ben; Barnes, David; Paling, David; Silber, Eli; Overell, James; Craner, Matthew; Carlson, Aaron; Wolff, Adam; Onuoha, Adaeze; Subei, Adnan; Ata, Ahmad; Borazanci, Aimee; Dastagir, Akram; Vasquez, Alberto; Alison Brooke Allen, ; Andrew, P Keegan; Carrasco, Angel; Angel, R Chinea Martinez; Bass, Ann; Okai, Annette; Erwin, April; Antezana-Antezana, Ariel; Green, Barbara; Bharathy, E Sundaram; Khatri, Bhupendra; Dihenia, Bhupesh; Gheorghiu, Bogdan; Costell, Brian; Steingo, Brian; Bruce, L Hughes; Carrie, M Hersh; Laganke, Christopher; Luzzio, Christopher; Ford, Corey; Craig Edward Herrman, ; Senzon, Craig; Huffman, Cynthia; Daniel, R Wynn; David D, O Bear; Lesch, David; David, H Mattson; Weisman, David; Deborah, A Burke; Dennis, W Dietrich; Huang, Deren; Robertson, Derrick; Lotfi, Djamchid; Don Joseph Alfonso, ; Stefoski, Dusan; Edward, J Fox; Pharr, Emily; Alvarez, Enrique; Bernitsas, Evanthia; Amjad, Faria; Pardo, Gabriel; Eubank, Geoffrey; Mcintosh, Gerald; Giles, F Crowell; Rao, Hemanth; J Michael Hemphill, ; Jack, H Florin; Nicholas, Jacqueline; Napier, James; Scott, James; Jason, M Silversteen; Vasallo, Javier; Schneider, Jean-Raphael; Wendt, Jeanette; Cohen, Jeffrey; Gross, Jeffrey; Groves, Jeffrey; Kaplan, Jeffrey; Stulc, Jessica; Joanna, A Cooper; Foley, John; Scagnelli, John; Jonathan, C Calkwood; Jose Pizarro Otero, ; Rafecas, Jose; Katz, Joshua; Juliette, S Saad; Standley, Katherine; Edwards, Keith; Sharlin, Kenneth; Bashir, Khurram; Wagner, Kimberly; Liow, Kore; Larry Lee Blankenship Jr, ; Mate, Laszlo; Montoya, Liliana; Lon, D Lynn; Agius, Mark; Cascione, Mark; Mark Allan Goldstein, ; Janicki, Mark; Martin, R Bialow; Mary Denise Hughes, ; Matthew, J Baker; Apperson, Michelle; Michelle, B Kuczma; M Mateo Paz Soldan, ; Cerghet, Mirela; Nathaniel Robb Whaley, ; Paul, K Winner; Repovic, Pavle; Kelkar, Praful; Romero Rekha Pillai, ; Ayala, Ricardo; Sater, Richard; Trudell, Randall; Robert Fairborn Armstrong, ; Robert Thomas Nahouraii, ; Naismith, Robert; Ronald, S Murray; Hunter, Samuel; Qureshi, Sara; Lynch, Sharon; Wray, Sibyl; Silvia, R Delgado; Donlon, Stacy; Cohan, Stanley; Smith, Stanya; Stuart James Shafer, ; Azalone, Susan; Hibbs, Susan; Tamara, A Miller; Giancarlo, Thomas; Desai, Troy; Varun, K Saxena; Simnad, Virginia; William David Honeycutt, ; Logan, William; William, E McElveen; Wagner, William. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 383:6(2020), pp. 546-557. [10.1056/NEJMoa1917246]

Ofatumumab versus Teriflunomide in Multiple Sclerosis

Francesco Sacca;
2020

Abstract

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.).
2020
Ofatumumab versus Teriflunomide in Multiple Sclerosis / Hauser, S. L.; Bar-Or, A.; Cohen, J. A.; Comi, G.; Correale, J.; Coyle, P. K.; Cross, A. H.; de Seze, J.; Leppert, D.; Montalban, X.; Selmaj, K.; Wiendl, H.; Kerloeguen, C.; Willi, R.; Li, B.; Kakarieka, A.; Tomic, D.; Goodyear, A.; Pingili, R.; Haring, D. A.; Ramanathan, K.; Merschhemke, M.; Kappos, L.; Stephen, L Hauser; Kappos, Ludwig; Bar-Or, Amit; Jeffrey, A Cohen; Comi, Giancarlo; Correale, Jorge; Patricia, K Coyle; Cross, Anne; Jerome de Seze, ; Montalban, Xavier; Selmaj, Krzysztof; Wiendl, Heinz; Stephen, C Reingold; Garry, R Cutter; Doerner, Thomas; Hartung, Hans-Peter; Per Soelberg Sørensen, ; Steiner, Israel; Jerry, S Wolinsky; Ballario, Carlos; Christian Calvo Vildoso, ; Jorge Gustavo Jose, ; Norma Haydee Deri, ; Liwacki, Susana; Lechner-Scott, Jeannette; Parratt, John; Hodgkinson, Suzanne; Maida, Eva-Maria; Leutmezer, Fritz; Willekens, Barbara; Bart Van Wijmeersch, ; Laureys, Guy; Caekebeke, Jo; Geens, Karine; Vanopdenbosch, Ludo; Deryck, Olivier; Delvaux, Valerie; Vincent Van Pesch, ; Milanov, Ivan; Tarnev, Ivaylo; Haralanov, Lyubomir; Maria Manova Slavova, ; Shotekov, Penko; Emond, Francois; Grandmaison, Francois; Jacques, Francois; Lee, Liesly; Marie Sarah Gagne Brosseau, ; Freedman, Mark; Cloutier, Martin; Carruthers, Robert; Morrow, Sarah; Lapierre, Yves; Vladic, Anton; Bokun, Hana; Antoncic, Igor; Marija Bosnjak Pasic, ; Habek, Mario; Silva Butkovic Soldo, ; Vuletic, Vladimira; Martinkova, Alena; Meluzinova, Eva; Stetkarova, Ivana; Mares, Jan; Markova, Jolana; Vachova, Marta; Valis, Martin; Tyblova, Michaela; Dufek, Michal; Skoda, Ondrej; Hradilek, Pavel; Ana Voldsgaard Jensen, ; Helle Hvilsted Nielsen, ; Svendsen, Kristina; Ravnborg, Mads; Peter Vestergaard Rasmussen, ; Gross-Paju, Katrin; Haldre, Sulev; Juha Pekka Eralinna, ; Sumelahti, Marja-Liisa; Brochet, Bruno; Louapre, Celine; Lebrun-Frenay, Christine; David Axel Laplaud, ; Edan, Gilles; Castelnovo, Giovanni; Debouverie, Marc; Vermersch, Patrick; Clavelou, Pierre; Labauge, Pierre; Berthele, Achim; Haghikia, Aiden; Kornhuber, Anselm; Bergmann, Arnfin; Frank, Benedikt; Elias-Hamp, Birte; Tackenberg, Bjoern; Wildemann, Brigitte; Strauss, Erik; Schlegel, Eugen; Florian Then Bergh, ; Nelles, Gereon; Tumani, Hayrettin; Sigel, Karl-Otto; Stangel, Martin; Boehringer, Matthias; Olaf Martin Hoffmann, ; Oschmann, Patrick; Hohlfeld, Reinhard; Walter, Silke; Menck, Sylvia; Sprenger, Till; Ziemssen, Tjalf; Veit Ulrich Becker, ; Straeten, Vera; Kilidireas, Konstantinos; Voumvourakis, Konstantinos; Fakas, Nikolaos; Grigoriadis, Nikolaos; Koves, Agnes; Rozsa, Csilla; Kovacs, Krisztina; Vecsei, Laszlo; Maria, Satori; Biro, Zita; Rohatgi, Anshu; Khurana, Dheeraj; Jeyaraj Durai Pandian, ; Joy Dev Mukherji, ; Pandit, Lekha; Meena Angamuthu Kanikannan, ; Ghosh, Pahari; Chakor, Rahul; Kulkarni, Rahul; Gursahani, Roopkumar; Ravat, Sangeeta; Rangasetty, Srinivasa; Kumar, Suresh; Shifrin, Alla; Karni, Arnon; Shahien, Radi; Milo, Ron; Uccelli, Antonio; Pozzilli, Carlo; Sacca, Francesco; Lus, Giacomo; Girolama Alessandra Marfia, ; Brambilla, Laura; Salvetti, Marco; Filippi, Massimo; Zaffaroni, Mauro; Gallo, Paolo; Rossi, Silvia; Bonavita, Simona; Studer, Valeria; Millers, Andrejs; Karelis, Guntis; Kalnina, Jolanta; Mickeviciene, Dalia; Kizlaitiene, Rasa; Angelica Carbajal Ramirez, ; Juan Jose Lopez Prieto, ; Wokke, Beatrijs; Bob, W Van Oosten; Peter Van Domburg, ; Hupperts, Raymond; Rogier, Q Hintzen; Edland, Astrid; Castaneda, Cesar; Perez, Julio; Gavidia, Martin; Wiak, Andrzej; Karaszewski, Bartosz; Jasinska, Elzbieta; Halina Bartosik Psujek, ; Jastrzebska, Iwona; Slawek, Jaroslaw; Maciejowski, Maciej; Dziki, Miroslaw; Monika Adamczyk Sowa, ; Bonek, Robert; Fryze, Waldemar; Ana Martins Da Silva, ; Timoteo, Angela; Antonio Vasco Salgado, ; Capela, Carlos; Veira, Carlos; Correia, Filipe; Cerqueira, Joao; Joao De Sa, ; Livia De Sousa, ; Gouveia, Raquel; Alina Sergeevna Agafina, ; Anna Naumovna Belova, ; Denis Viktorovich Sazonov, ; Pokhabov, Dmitry; Ekaterina Igorevna Kairbekova, ; Elena Gennadievna Arefieva, ; Farit Axatovich Khabirov, ; Igor Vyacheslavovich Litvinenko, ; Stolyarov, Igor; Irina Aleksandrovna Sokolova, ; Larisa Ivanovna Volkova, ; Maria Vafaevna Davydovskaya, ; Maria Nikolaevna Zaharova, ; Nadezhda Alekseevna Malkova, ; Natalia Agafonovna Totolyan, ; Nikolay Vasilievich Dorogov, ; Stella Anatolievna Sivertseva, ; Kurca, Egon; Krastev, Georgi; Brozman, Miroslav; Koleda, Peter; Turcani, Peter; Valkovic, Peter; Hancinova, Viera; Donath, Vladimir; Retief, Chris; Isaacs, Michael; Albert Saiz Hinarejos, ; Alfredo Rodriguez Antigüedad, ; Bonaventura Casanova Estruch, ; Oreja-Guevara, Celia; Gemma Reig Rosello, ; Jose Carlos Alvarez Cermeño, ; Jose Martinez Rodriguez, ; Jose Meca Lallana, ; Juan Antonio Garcia Merino, ; Lucia Forero Diaz, ; Lucienne Costa Frossard Franca, ; Luis Querol Gutierrez, ; Lluis Ramio Torrenta, ; Pedro Serrano Castro, ; Rafael Arroyo Gonzalez, ; Sara Eichau Madueño, ; Sergio Martinez Yelamos, ; Tamara Castillo Trivino, ; Virgina Meca Lallana, ; Xaviere Montalban Gairin, ; Piehl, Fredrik; Lycke, Jan; Zecca, Chiara; Derfuss, Tobias; Lin, Thy-Sheng; Tiamkao, Somsak; Ayse Nur Yuceyar, ; Soysal, Aysun; Belgin Petek Balci, ; Boz, Cavit; Efendi, Husnu; Terzi, Murat; Sevim, Serhan; Ozakbas, Serkan; Gale, Andrew; Turner, Ben; Barnes, David; Paling, David; Silber, Eli; Overell, James; Craner, Matthew; Carlson, Aaron; Wolff, Adam; Onuoha, Adaeze; Subei, Adnan; Ata, Ahmad; Borazanci, Aimee; Dastagir, Akram; Vasquez, Alberto; Alison Brooke Allen, ; Andrew, P Keegan; Carrasco, Angel; Angel, R Chinea Martinez; Bass, Ann; Okai, Annette; Erwin, April; Antezana-Antezana, Ariel; Green, Barbara; Bharathy, E Sundaram; Khatri, Bhupendra; Dihenia, Bhupesh; Gheorghiu, Bogdan; Costell, Brian; Steingo, Brian; Bruce, L Hughes; Carrie, M Hersh; Laganke, Christopher; Luzzio, Christopher; Ford, Corey; Craig Edward Herrman, ; Senzon, Craig; Huffman, Cynthia; Daniel, R Wynn; David D, O Bear; Lesch, David; David, H Mattson; Weisman, David; Deborah, A Burke; Dennis, W Dietrich; Huang, Deren; Robertson, Derrick; Lotfi, Djamchid; Don Joseph Alfonso, ; Stefoski, Dusan; Edward, J Fox; Pharr, Emily; Alvarez, Enrique; Bernitsas, Evanthia; Amjad, Faria; Pardo, Gabriel; Eubank, Geoffrey; Mcintosh, Gerald; Giles, F Crowell; Rao, Hemanth; J Michael Hemphill, ; Jack, H Florin; Nicholas, Jacqueline; Napier, James; Scott, James; Jason, M Silversteen; Vasallo, Javier; Schneider, Jean-Raphael; Wendt, Jeanette; Cohen, Jeffrey; Gross, Jeffrey; Groves, Jeffrey; Kaplan, Jeffrey; Stulc, Jessica; Joanna, A Cooper; Foley, John; Scagnelli, John; Jonathan, C Calkwood; Jose Pizarro Otero, ; Rafecas, Jose; Katz, Joshua; Juliette, S Saad; Standley, Katherine; Edwards, Keith; Sharlin, Kenneth; Bashir, Khurram; Wagner, Kimberly; Liow, Kore; Larry Lee Blankenship Jr, ; Mate, Laszlo; Montoya, Liliana; Lon, D Lynn; Agius, Mark; Cascione, Mark; Mark Allan Goldstein, ; Janicki, Mark; Martin, R Bialow; Mary Denise Hughes, ; Matthew, J Baker; Apperson, Michelle; Michelle, B Kuczma; M Mateo Paz Soldan, ; Cerghet, Mirela; Nathaniel Robb Whaley, ; Paul, K Winner; Repovic, Pavle; Kelkar, Praful; Romero Rekha Pillai, ; Ayala, Ricardo; Sater, Richard; Trudell, Randall; Robert Fairborn Armstrong, ; Robert Thomas Nahouraii, ; Naismith, Robert; Ronald, S Murray; Hunter, Samuel; Qureshi, Sara; Lynch, Sharon; Wray, Sibyl; Silvia, R Delgado; Donlon, Stacy; Cohan, Stanley; Smith, Stanya; Stuart James Shafer, ; Azalone, Susan; Hibbs, Susan; Tamara, A Miller; Giancarlo, Thomas; Desai, Troy; Varun, K Saxena; Simnad, Virginia; William David Honeycutt, ; Logan, William; William, E McElveen; Wagner, William. - In: THE NEW ENGLAND JOURNAL OF MEDICINE. - ISSN 0028-4793. - 383:6(2020), pp. 546-557. [10.1056/NEJMoa1917246]
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