Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

B Rup; M Pallardy; D Sikkema; T Albert; M Allez; P Broet; C Carini; P Creeke; J Davidson; N De Vries; D Finco; A Fogdell-Hahn; E Havrdova; A Hincelin-Mery; M C Holland; P E H Jensen; E C Jury; H Kirby; D Kramer; S Lacroix-Desmazes; J Legrand; E Maggi; B Maillère; X Mariette; C Mauri; V Mikol; D Mulleman; J Oldenburg; G Paintaud; C R Pedersen; N Ruperto; R Seitz; S Spindeldreher; F Deisenhammer; ABIRISK Consortium

doi:10.1111/cei.12652

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Clin Exp Immunol. 2015 Sep;181(3):385-400. doi: 10.1111/cei.12652. Epub 2015 Jul 2.

Authors

B Rup¹, M Pallardy², D Sikkema³, T Albert⁴, M Allez⁵, P Broet⁶, C Carini⁷, P Creeke⁸, J Davidson⁹, N De Vries¹⁰, D Finco¹¹, A Fogdell-Hahn¹², E Havrdova¹³, A Hincelin-Mery¹⁴, M C Holland¹⁵, P E H Jensen¹⁶, E C Jury¹⁷, H Kirby¹⁸, D Kramer¹⁹, S Lacroix-Desmazes²⁰, J Legrand²¹, E Maggi²², B Maillère²³, X Mariette²⁴, C Mauri²⁵, V Mikol²⁶, D Mulleman²⁷, J Oldenburg⁴, G Paintaud²⁸, C R Pedersen²⁹, N Ruperto³⁰, R Seitz³¹, S Spindeldreher³², F Deisenhammer³³; ABIRISK Consortium

Affiliations

¹ Pfizer, Immunogenicity Sciences Disciple, Pharmacokinetics, Dynamics and Metabolism.
² INSERM, UMR996, Faculté Pharmacie, Université Paris Sud, France.
³ GlaxoSmithKline, Clinical Immunology-Biopharm, King of Prussia, PA, USA.
⁴ Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
⁵ Hôpital Saint-Louis, Department of Gastroenterology, GETAID, Paris, France.
⁶ INSERM, UMR669, University of Paris Sud, France.
⁷ Pfizer, Early Biotech Clinical Development, Cambridge, MA, USA.
⁸ Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK.
⁹ GlaxoSmithKline, Worldwide Epidemiology, Southall, UK.
¹⁰ Clinical Immunology and Rheumatology, University of Amsterdam, Amsterdam, the Netherlands.
¹¹ Pfizer, Drug Safety R&D, Groton, CT, USA.
¹² Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹³ Department of Neurology and Center for Clinical Neuroscience, MS Center, Charles University in Prague, Prague, Czech Republic.
¹⁴ Sanofi-Aventis, Clinical Exploratory and Pharmacology, Chilly-Mazerin, FR.
¹⁵ GlaxoSmithKline, Clinical Immunology-Biopharm R&D, King of Prussia, PA, USA.
¹⁶ Department of Neurology, University of Copenhagen, Copenhagen, Denmark.
¹⁷ Centre for Rheumatology, University College London, London, UK.
¹⁸ UCB Pharma, Bioanalytical R&D, Slough, UK.
¹⁹ Merck-Serono, Institute of Drug Metabolism and Pharmacokinetics, Grafing, Germany.
²⁰ INSERM, UMR S 1138, Université Pierre et Marie Curie, Paris, France.
²¹ Ipsen Innovation, Pharmacokinetics Drug Metabolism Department, Les Ulis, France.
²² Dipartimento di Medicina Sperimentale e Clinica, Universita di Firenze, Firenze, Italy.
²³ CEA-Saclay Institute of Biology and Technologies, Gif sur Yvette, France.
²⁴ INSERM, U1012, Hôpitaux Universitaires Paris Sud, Rhumatologie, Paris, France.
²⁵ Centre for Rheumatology Research, University College London, London, UK.
²⁶ Sanofi Aventis, Structural Biology, Paris, France.
²⁷ University of Tours Francois Rabelais, CNRS UMR 7292, Tours, France.
²⁸ CNRS UMR 7292 'GICC', Faculty of Medicine, Tours, France.
²⁹ Novo Nordisk, Immunogenicity, Måløv, Denmark.
³⁰ Istituto Giannina Gaslini, Pediatria II, Rheumatology, Genova, Italy.
³¹ Division of Haematology/Transfusion Medicine, Paul-Ehrlich-Institut, Langen, Germany.
³² Drug Metabolism Pharmacokinetics-Biologics, Novartis Institutes for Biomedical Research, Basel, Switzerland.
³³ Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

Abstract

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti-Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

Keywords: ABIRISK consortium; anti-drug antibodies; biopharmaceuticals; immunogenicity.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Allergy and Immunology / standards
Drug Hypersensitivity / immunology
Drug Hypersensitivity / prevention & control*
Drug Industry / organization & administration
Drug Industry / standards
Drugs, Investigational / adverse effects
Drugs, Investigational / standards*
Drugs, Investigational / therapeutic use
Guidelines as Topic / standards*
Humans
Organizational Innovation
Organizational Policy
Reference Standards
Terminology as Topic*

Substances

Drugs, Investigational

Abstract

Publication types

MeSH terms

Substances

Grants and funding