Rieke Alten1, Colin Markland2, Malcolm Boyce3, Kazuki Kawakami4, Rafael Muniz5, Mark C Genovese6. 1. University Medicine Berlin, Berlin, Germany. 2. NDA Group, Leatherhead, UK. 3. Hammersmith Medicines Research, London, UK. 4. Fujifilm Kyowa Kirin Biologics, Tokyo, Japan. 5. Mylan Inc, Canonsburg, PA, USA. 6. Stanford University, Palo Alto, CA, USA.
Abstract
AIM: This study, FKB327-003, is a phase 3, open-label extension (OLE) study comparing the long-term immunogenicity of an adalimumab biosimilar, FKB327 (F), with the reference product (RP). METHODS: In the OLE, patients completing 24 weeks of an initial randomized, double-blind (DB) study (Period 1) with clinical response and no safety concerns were rerandomized to F or RP, so that two-thirds of patients remained on the same treatment and one-third switched to the alternate treatment for weeks 24 through 54 (OLE weeks 0-30; Period 2), then all received F through week 100 (OLE week 76; Period 3). Treatment sequences were F-F-F (no switch), RP-F-F and RP-RP-F (single switch), and F-RP-F (double switch). Patients who entered the OLE study were evaluated for immunogenicity across switching sequences. RESULTS: The proportion of patients with positive antidrug antibody (ADA) status at the end of Period 1 was 61.7% and 60.0% for F and RP, respectively. The proportion of patients with positive ADA status did not increase throughout Period 1, and was similar for F and RP at all time points. At the end of Period 3, the proportion of patients with positive ADA status was lower in all treatment sequences, at 51.1%, 54.4%, 48.1%, and 42.5% for F-F-F, F-RP-F, RP-F-F, and RP-RP-F, respectively. CONCLUSION: The RP and F showed comparable immunogenicity characteristics after long-term administration. Development of ADAs with the RP and F was similar, and was not impacted by switching and double switching between F and RP treatment.
RCT Entities:
AIM: This study, FKB327-003, is a phase 3, open-label extension (OLE) study comparing the long-term immunogenicity of an adalimumab biosimilar, FKB327 (F), with the reference product (RP). METHODS: In the OLE, patients completing 24 weeks of an initial randomized, double-blind (DB) study (Period 1) with clinical response and no safety concerns were rerandomized to F or RP, so that two-thirds of patients remained on the same treatment and one-third switched to the alternate treatment for weeks 24 through 54 (OLE weeks 0-30; Period 2), then all received F through week 100 (OLE week 76; Period 3). Treatment sequences were F-F-F (no switch), RP-F-F and RP-RP-F (single switch), and F-RP-F (double switch). Patients who entered the OLE study were evaluated for immunogenicity across switching sequences. RESULTS: The proportion of patients with positive antidrug antibody (ADA) status at the end of Period 1 was 61.7% and 60.0% for F and RP, respectively. The proportion of patients with positive ADA status did not increase throughout Period 1, and was similar for F and RP at all time points. At the end of Period 3, the proportion of patients with positive ADA status was lower in all treatment sequences, at 51.1%, 54.4%, 48.1%, and 42.5% for F-F-F, F-RP-F, RP-F-F, and RP-RP-F, respectively. CONCLUSION: The RP and F showed comparable immunogenicity characteristics after long-term administration. Development of ADAs with the RP and F was similar, and was not impacted by switching and double switching between F and RP treatment.
Authors: Margreet H Hart; Henk de Vrieze; Diana Wouters; Gerrit-Jan Wolbink; Joep Killestein; Els R de Groot; Lucien A Aarden; Theo Rispens Journal: J Immunol Methods Date: 2011-07-29 Impact factor: 2.303
Authors: Pauline A van Schouwenburg; Lotte A van de Stadt; Rob N de Jong; Esther E L van Buren; Simone Kruithof; Els de Groot; Margreet Hart; S Marieke van Ham; Theo Rispens; Lucien Aarden; Gerrit Jan Wolbink; Diana Wouters Journal: Ann Rheum Dis Date: 2012-07-03 Impact factor: 19.103
Authors: Jeannie R Rojas; Ronald P Taylor; Mark R Cunningham; Thomas J Rutkoski; Joseph Vennarini; Haishan Jang; Martin A Graham; Karel Geboes; Serge D Rousselle; Carrie L Wagner Journal: J Pharmacol Exp Ther Date: 2005-01-12 Impact factor: 4.030
Authors: A Vultaggio; A Matucci; F Nencini; S Pratesi; P Parronchi; O Rossi; S Romagnani; E Maggi Journal: Allergy Date: 2009-11-27 Impact factor: 13.146
Authors: Mark C Genovese; Josephine Glover; Maria Greenwald; Wieslawa Porawska; Elias Chalouhi El Khouri; Eva Dokoupilova; Juan Ignacio Vargas; Mykola Stanislavchuk; Herbert Kellner; Elena Baranova; Nobuhito Matsunaga; Rieke Alten Journal: Arthritis Res Ther Date: 2019-12-12 Impact factor: 5.156
Authors: Rieke Alten; Colin Markland; Malcolm Boyce; Kazuki Kawakami; Rafael Muniz; Mark C Genovese Journal: Int J Rheum Dis Date: 2020-08-27 Impact factor: 2.454
Authors: Rieke Alten; Colin Markland; Malcolm Boyce; Kazuki Kawakami; Rafael Muniz; Mark C Genovese Journal: Int J Rheum Dis Date: 2020-08-27 Impact factor: 2.454