title: The scientific and regulatory rationale for indication extrapolation: a case study based on the infliximab biosimilar CT-P13.
abstract: Extrapolation of clinical data from other indications is an important concept in the development of biosimilars. This process depends on strict comparability exercises to establish similarity to the reference medicinal product. However, the extrapolation paradigm has prompted a fierce scientific debate. CT-P13 (Remsima(®), Inflectra(®)), an infliximab biosimilar, is a TNF antagonist used to treat immune-mediated inflammatory diseases. On the basis of totality of similarity data, the EMA approved CT-P13 for all indications held by its reference medicinal product (Remicade(®)) including inflammatory bowel disease. This article reviews the mechanisms of action of TNF antagonists in immune-mediated inflammatory diseases and illustrates the comparable profiles of CT-P13 and reference medicinal product on which the extrapolation of indications including inflammatory bowel disease is based.
authors.affiliation: a 1 Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: b 2 Department of Gastroenterology, University Hospital CHU of Liege, Liege, Belgium.
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.affiliation: c 3 Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017277:Drug Approval; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000069285:Infliximab / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D014018:Tissue Distribution; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D059451:Biosimilar Pharmaceuticals; C000591237:CT-P13; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: CT-P13; biosimilar; extrapolation; inflammatory bowel disease; infliximab; mechanism of action; pharmacokinetics