Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease

Abstract

Background and Aims Biosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn's disease (CD), has reduced direct drug costs. Though clinicians are comfortable with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13. Methods A literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance. Results A total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects. Conclusions The majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.

Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective

“…However, immunogenicity is often presented as the main and unpredictable risk of biosimilars in spite of the questionable theoretical basis and lack of any supporting clinical evidence for this hypothesis [13,38,41]. Furthermore, much of the discussion on interchangeability has been focused on the requirement for extensive studies with multiple switches, as well as switches between biosimilars of the same reference product [39][40][41][42][43][44][45][46][47][48][49][50][51]. Such studies would require hundreds of patients per study, which will discourage the development of biosimilars [32,41].…”

Potential Cost Implications of Mandatory Non‐Medical Switching Policies for Biologics for Rheumatic Conditions and Inflammatory Bowel Disease in Canada

“…The evidence to support the appropriateness of nonmedical switching is growing. Although the approval of infliximab, etanercept, and adalimumab biosimilars in Canada was based on clinical trials in patients with rheumatic or dermatologic conditions, postmarket switching studies suggest that patients using infliximab or adalimumab for IBD can also be switched to currently marketed biosimilars without causing harm related to efficacy, safety, or immunogenicity 16–22 . Although the majority of IBD‐specific studies were observational, health authorities and medical associations in other jurisdictions now support switching practices for all indications 23–26 .…”

“…Although the approval of infliximab, etanercept, and adalimumab biosimilars in Canada was based on clinical trials in patients with rheumatic or dermatologic conditions, postmarket switching studies suggest that patients using infliximab or adalimumab for IBD can also be switched to currently marketed biosimilars without causing harm related to efficacy, safety, or immunogenicity. [16][17][18][19][20][21][22] Although the majority of IBD-specific studies were observational, health authorities and medical associations in other jurisdictions now support switching practices for all indications. [23][24][25][26] However, there are also important logistical implications of switching patients on innovator biologics to biosimilars, as many patient support programs and infusion clinics are exclusive to patients on specific biologics and funded by the manufacturer.…”

Biosimilar Interchangeability and Emerging Treatment Strategies for Inflammatory Bowel Diseases: A Commentary

“…The nocebo effect may have an important impact on an increased discontinuation rate after switching in the absence of patient symptomatology [73,75]. Real-world studies of anti-TNF-α agents show higher discontinuation rates in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators [8,71,76]. In addition, there is evidence that the naming convention for biosimilars affects patients' perception of interchangeability.…”