Discontinuation Rates Following a Switch From a Reference to a Biosimilar Biologic in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Abstract

BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

Biosimilar knowledge and viewpoints among Brazilian inflammatory bowel disease patients

“…The most common causes of discontinuation were loss of response (5%) and adverse events (7%). 13 …”

“…The most common causes of discontinuation were loss of response (5%) and adverse events (7%). 13 This survey had several limitations. It was selfselective, only available online in a European website in eight languages (including Portuguese), which may have contributed to the low access of Brazilians to the questionnaire.…”

Prescriber Perspectives on Biosimilar Adoption and Potential Role of Clinical Pharmacology: A Workshop Summary

“… 52 Queiroz et al . 53 conducted a meta‐analysis of 30 observational studies involving a total of 3,594 patients with IBD to examine the impact of an innovator to biosimilar switch on discontinuation rates over time. All studies in the dataset included a minimum post‐switch follow‐up of > 6 months or 3 infusions.…”

“…As such, the nocebo effect may play an important role in the higher‐than expected discontinuation rates reported in patients with immune‐mediated disease who switched to the biosimilar CT‐P13 after being stabilized on an innovator treatment 52 . Queiroz et al 53 . conducted a meta‐analysis of 30 observational studies involving a total of 3,594 patients with IBD to examine the impact of an innovator to biosimilar switch on discontinuation rates over time.…”

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].…”