Grzegorz Kijanka1, Wim Jiskoot, Huub Schellekens, Vera Brinks. 1. Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences-UIPS, Utrecht University, David de Wied Building, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. g.m.kijanka@uu.nl
Abstract
PURPOSE: Interferon beta is commonly used as therapeutic in the first line of therapy for multiple sclerosis. However, depending on the product, it induces an antibody response in up to 60% of patients. This study evaluated the impact of therapy related factors like dose, route of administration and administration frequency on the immunogenicity of one of the originator interferon beta drugs (Betaferon®) in an immune tolerant transgenic mouse model. METHODS: Immune tolerant transgenic mice received injections with Betaferon® via different routes, doses and injection frequencies. Anti-drug antibody (ADA) production was measured by ELISA to assess immunogenicity. RESULTS: A single injection of Betaferon® was found to be sufficient for the induction of ADAs. The antibody titer was enhanced with increasing dose and treatment frequency. Among the tested administration routes, the intravenous route was the most immunogenic one, which is in contradiction with one of the dogma in immunogenicity research according to which subcutaneous administration is the most immunogenic route. Intramuscular, intraperitoneal and subcutaneous injections resulted in comparable immunogenicity. CONCLUSION: This study shows that treatment related factors affect significantly immunogenicity of Betaseron® and therefore substantiate the need for further studies on these factors in patients.
PURPOSE:Interferon beta is commonly used as therapeutic in the first line of therapy for multiple sclerosis. However, depending on the product, it induces an antibody response in up to 60% of patients. This study evaluated the impact of therapy related factors like dose, route of administration and administration frequency on the immunogenicity of one of the originator interferon beta drugs (Betaferon®) in an immune tolerant transgenicmouse model. METHODS: Immune tolerant transgenic mice received injections with Betaferon® via different routes, doses and injection frequencies. Anti-drug antibody (ADA) production was measured by ELISA to assess immunogenicity. RESULTS: A single injection of Betaferon® was found to be sufficient for the induction of ADAs. The antibody titer was enhanced with increasing dose and treatment frequency. Among the tested administration routes, the intravenous route was the most immunogenic one, which is in contradiction with one of the dogma in immunogenicity research according to which subcutaneous administration is the most immunogenic route. Intramuscular, intraperitoneal and subcutaneous injections resulted in comparable immunogenicity. CONCLUSION: This study shows that treatment related factors affect significantly immunogenicity of Betaseron® and therefore substantiate the need for further studies on these factors in patients.
Authors: L Runkel; W Meier; R B Pepinsky; M Karpusas; A Whitty; K Kimball; M Brickelmaier; C Muldowney; W Jones; S E Goelz Journal: Pharm Res Date: 1998-04 Impact factor: 4.200
Authors: M S Freedman; G S Francis; E A C M Sanders; G P A Rice; P O'Connor; G Comi; P Duquette; L Metz; T J Murray; J-P Bouchard; O Abramsky; J Pelletier; F O'Brien Journal: Mult Scler Date: 2005-02 Impact factor: 6.312
Authors: C Ross; K M Clemmesen; M Svenson; P S Sørensen; N Koch-Henriksen; G L Skovgaard; K Bendtzen Journal: Ann Neurol Date: 2000-11 Impact factor: 10.422
Authors: A Bertolotto; F Gilli; A Sala; M Capobianco; S Malucchi; E Milano; F Melis; F Marnetto; R L P Lindberg; R Bottero; A Di Sapio; M T Giordana Journal: Neurology Date: 2003-02-25 Impact factor: 9.910
Authors: P Perini; A Facchinetti; P Bulian; A R Massaro; D D Pascalis; A Bertolotto; G Biasi; P Gallo Journal: Eur Cytokine Netw Date: 2001-03 Impact factor: 2.737
Authors: Diane R Mould; Richard N Upton; Jessica Wojciechowski; Becky L Phan; Stacy Tse; Marla C Dubinsky Journal: AAPS J Date: 2018-06-14 Impact factor: 4.009
Authors: Carly Fleagle Chisholm; Abby E Baker; Kaitlin R Soucie; Raul M Torres; John F Carpenter; Theodore W Randolph Journal: J Pharm Sci Date: 2016-03-25 Impact factor: 3.534
Authors: Wim Jiskoot; Grzegorz Kijanka; Theodore W Randolph; John F Carpenter; Atanas V Koulov; Hanns-Christian Mahler; Marisa K Joubert; Vibha Jawa; Linda O Narhi Journal: J Pharm Sci Date: 2016-04-01 Impact factor: 3.534