Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases

Abstract

Summary Background Anti‐tumour necrosis factor (anti‐TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT‐P13; however, some uncertainty exists regarding their pharmacology in IBD. Aim To review the literature on anti‐TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. Methods A PubMed literature search was performed using the following terms individually or in combination: ‘biosimilars,’ ‘CT‐P13,’ ‘Crohn's disease,’ ‘inflammatory bowel disease,’ ‘ulcerative colitis,’ ‘anti‐TNFα therapy,’ ‘infliximab,’ ‘adalimumab,’ ‘pharmacokinetics,’ ‘immunogenicity.’ Results Bioequivalence of CT‐P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT‐P13 in IBD come from small post‐marketing registries and case series with a relatively short‐term follow‐up period and suggest comparable efficacy and safety to infliximab. Inter‐ and intra‐individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross‐reactivity of anti‐drug antibodies and whether similar exposure–response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. Conclusions It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post‐marketing studies and pharmacovigilance are warranted in the coming years.

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…This is because biologics are large and structurally complex, meaning that, unlike the characterisation of generics, current analytical methodology may not be able to detect or characterise all relevant structural and functional differences between biologics, a distinction that is also noted in the FDA guidance on demonstrating biosimilarity and the Australian Therapeutic Goods Administration (TGA) biologic nomenclature consultation [3, 11]. Data on the efficacy and safety of initiating therapy with a biosimilar versus with an originator biologic, generated as part of regulatory approval and post-approval phases, have been widely reviewed [12–14] and are not the focus of the current article.…”

Mesenchymal Stromal Cell Therapy in Crohn's Disease

“…Internationally, clinicians and authorities are presently grappling with the concept of using 'biosimilars' for patients with inflammatory bowel disease; biosimilars are molecules that are similar but not identical to the original biologic agent used [30] . Concern has been expressed about the possibility that slight molecular conformational change could have significant implications both for efficacy and for safety [31] .…”

Policy Practices to Maximise Social Benefit from Biosimilars

“…Additionally, debate on immunogenicity has been fuelled by manufacturers of original biologic medicines [29]. Recently, however, several systematic reviews evaluated the clinical consequences of switching to biosimilar medicines, but none of them concluded increased risk of adverse events or efficacy loss [30][31][32][33]. These reviews, along with evidence generated from recent clinical trials indicate that significant and quantifiable economic benefits from switching patients on maintenance biologic medicines to their biosimilar alternatives under medical supervision should not be sacrificed for non-quantifiable and fairly low risks of immunogenicity.…”

“…Overall, the opportunity cost of not switching patients to biosimilar medicines is greater in lower income than higher income countries, as health care budgets are more limited. Current evidence suggests that a single switch of patients treated with original biologic to biosimilar products after patent expiry is not associated with increased risk of adverse reactions or loss of efficacy [30][31][32][33]. When there is clinical trial or registry based evidence about continued efficacy and nonincreased adverse event rate after switching of a biological medicine to its biosimilar alternative, expedited review with CMA is sufficient to select the most cost-effective treatment strategy.…”