Does the Introduction of Biosimilars Change Our Understanding about Treatment Modalities for Inflammatory Bowel Disease?

Abstract

Background: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use. Conclusions: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics.

Use of Biosimilars in Pediatric Inflammatory Bowel Disease

“…In clinical practice, extrapolation of molecules in the same class sharing the same mechanism of action from adult to pediatric (6,7) or across indications (8,9) is common in case there are not enough data available or when clinical trials are ongoing. Extrapolation allows keeping the cost of BioS competitive with subsequent greater market availability (4,10,11). On the other hand, proven mechanism of action (eg, TNF blocking) in different diseases may not result in same clinical efficacy (9,12,13).…”

“…As IBD is a complex disease with differences between pediatric-onset and adult-onset disease, the decisions of regulatory agencies on extrapolation of indications to IBD were challenged by both adult (ECCO) and pediatric (ESPGHAN) gastroenterology societies (14,15). In 2014, Health Canada did not approve IFX BioS for IBD due to lack of clinical data, molecular glycosylation differences and uncertainty resulting from small differences in antibody-dependent cell-mediated cytotoxicity (9,10,(16)(17)(18). However, in view of the emerging data, Health Canada has now recommended BioS IFX for all the indications of originator IFX by extrapolation (19).…”

“…Performing RCTs with BioS in all extrapolated indications is very costly and time consuming, thus available evidence will mainly accumulate post-market, non-controlled, observational trials. Since BioS approval by regulatory agencies, a number of clinical data reports were published on BioS in both adult and paediatric IBD (10,(25)(26)(27)(28)(29)(30)(31)(32)(33) but no major clinical trials have compared the efficacy of IFX originator and its BioS specifically in patients with IBD (10). The NOR-SWITCH RCT trial (34) found comparable safety and efficacy in patients with various diagnoses (including IBD) switching from IFX to CT-P13.…”

Characteristics of biological therapy in pediatric patients with Crohn’s disease

“…The patent for the IFX originator administration of these agents vary substantially between countries. For example, Health Canada (2014) did not approve IFX BS for IBD due to insufficient amount of clinical data, molecular glycosylation differences and uncertainty resulting from small differences in antibody-dependent cell-mediated cytotoxicity [92][93][94][95][96]. Nevertheless, in view of the emerging data, Health Canada has now recommended BS IFX for all the indications of originator IFX by extrapolation [97].…”

“…Nevertheless, in view of the emerging data, Health Canada has now recommended BS IFX for all the indications of originator IFX by extrapolation [97]. In other countries, BS approval by regulatory agencies, a number of clinical data reports were published on BS in both adult and pediatric IBD [93,[98][99][100][101][102][103][104][105][106]. The NOR-SWITCH RCT trial [107] found comparable safety and efficacy in patients including IBD switching from IFX to CT-P13.…”