title: Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation.
abstract: Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD.
authors.affiliation: Gastroenterology Department, Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Tel Hashomer, Israel. Electronic address: shomron.benhorin@gmail.com.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; Division of Gastroenterology, University of California San Diego, La Jolla, California.
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.affiliation: Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.affiliation: First Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
mesh_terms: D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use*; D017277:Drug Approval; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*
chemical_list: D059451:Biosimilar Pharmaceuticals; D005765:Gastrointestinal Agents; D007155:Immunologic Factors
keywords: Biosimilar; CT-P13; Extrapolation; Inflammatory Bowel Disease; Infliximab; Infliximab-dyyb