The principal results of the International Immune Tolerance Study: a randomized dose comparison
Charles R M Hay, Donna M DiMichele, International Immune Tolerance Study, Thomas C Abshire, Geoff Allen, Irmel Ayala, José Antonio Aznar, Dorothy Barnard, Carolyn Bennett, Manuel Carcao, Alice J Cohen, Peter Collins, Christine Demers, Amy Dunn, Miguel Escobar, Nadia Ewing, Brian Feldman, Frances Flug, Joan Gill, Anders Glomstein, Jenny Goudemand, Gunwant Guron, John Hanley, Margaret Heisel, Keith Hoots, Jeffrey Hord, Anne Hurlet, Eisaburo Ishii, David Keeling, Gili Kenet, Bryce Kerlin, Robert Klaassen, Maseo Kobayashi, Ryokji Kobayashi, Roshi Kulkarni, Cindy A Leissinger, Lianne Lockwood, Marilyn Manco-Johnson, Catherine Manno, Prasad Mathew, Tadashi Matsushita, Evelien Mauser-Bunschotten, Paul E Monahan, Massimo Morfini, Anne Neff, Ellis Neufeld, Diane Nugent, Chiai Oi, Yuri Okimoto, Rafael Parra, Kathelijne Peerlinck, Steven Pipe, Man-Chiu Poon, Leslie Raffini, Margaret Ragni, Michael Recht, Ulrike Reiss, Bruce Ritchie, Georges-Etienne Rivard, Vilamarie Rodriguez, Cathy Rosenfield, Anne Rossi, Elena Santagostino, Frank Shafer, Amy Shapiro, Midori Shima, Akira Shimada, Akira Shirahata, Takashi Suzuki, Kyoko Takeichi, Michael Tarantino, A E Thomas, Alexis Thompson, Ikuya Usami, Tamaki Ueno, Leonard A Valentino, Mareike van den Berg, Raymond Watts, Eric J Werner, Brian Wicklund, Charles R M Hay, Donna M DiMichele, International Immune Tolerance Study, Thomas C Abshire, Geoff Allen, Irmel Ayala, José Antonio Aznar, Dorothy Barnard, Carolyn Bennett, Manuel Carcao, Alice J Cohen, Peter Collins, Christine Demers, Amy Dunn, Miguel Escobar, Nadia Ewing, Brian Feldman, Frances Flug, Joan Gill, Anders Glomstein, Jenny Goudemand, Gunwant Guron, John Hanley, Margaret Heisel, Keith Hoots, Jeffrey Hord, Anne Hurlet, Eisaburo Ishii, David Keeling, Gili Kenet, Bryce Kerlin, Robert Klaassen, Maseo Kobayashi, Ryokji Kobayashi, Roshi Kulkarni, Cindy A Leissinger, Lianne Lockwood, Marilyn Manco-Johnson, Catherine Manno, Prasad Mathew, Tadashi Matsushita, Evelien Mauser-Bunschotten, Paul E Monahan, Massimo Morfini, Anne Neff, Ellis Neufeld, Diane Nugent, Chiai Oi, Yuri Okimoto, Rafael Parra, Kathelijne Peerlinck, Steven Pipe, Man-Chiu Poon, Leslie Raffini, Margaret Ragni, Michael Recht, Ulrike Reiss, Bruce Ritchie, Georges-Etienne Rivard, Vilamarie Rodriguez, Cathy Rosenfield, Anne Rossi, Elena Santagostino, Frank Shafer, Amy Shapiro, Midori Shima, Akira Shimada, Akira Shirahata, Takashi Suzuki, Kyoko Takeichi, Michael Tarantino, A E Thomas, Alexis Thompson, Ikuya Usami, Tamaki Ueno, Leonard A Valentino, Mareike van den Berg, Raymond Watts, Eric J Werner, Brian Wicklund
Abstract
The International Immune Tolerance Study was a multicenter, prospective, randomized comparison of high-dose (HD; 200 IU/kg/d) and low-dose (LD; 50 IU/kg 3 times/week) factor VIII regimens in 115 "good-risk," severe high-titer inhibitor hemophilia A subjects. Sixty-six of 115 subjects reached the defined study end points: success, n = 46 (69.7%); partial response, n = 3 (4.5%); and failure, n = 17 (25.8%). Successes did not differ between treatment arms (24 of 58 LD vs 22/57 HD, P = .909). The times taken to achieve a negative titer (P = .027), a normal recovery (P = .002), and tolerance (P = .116, nonsignificant) were shorter with the HD immune tolerance induction (ITI). Peak historical (P = .026) and on-ITI (P = .002) titers were correlated inversely with success, but only peak titer on ITI predicted outcome in a multivariate analysis (P = .002). LD subjects bled more often (odds ratio, 2.2; P = .0019). The early bleed rate/month was 0.62 (LD) and 0.28 (HD; P = .000 24), decreasing by 90% once negative titers were achieved. Bleeding was absent in 8 of 58 LD versus 21 of 57 HD subjects (P = .0085). One hundred twenty-four central catheter infections were reported in 41 subjects (19 LD); infection frequency did not differ between the treatment arms. Neither bleeding nor infection influenced outcome. Although it was stopped early for futility and safety considerations, this trial contributed valuable data toward evidence-based ITI practice.
Source: PubMed