Patients Retransitioning from Biosimilar TNFα Inhibitor to the Corresponding Originator After Initial Transitioning to the Biosimilar: A Systematic Review

Abstract

Background Transitioning patients from an originator to a corresponding biosimilar has been extensively studied in both randomized controlled trials and observational studies. Although transitioning is considered well-tolerated, with no negative impacts on efficacy and/or safety, 2.6-25.8% of patients restart treatment with the originator (retransitioning). Retransitioning to the originator can be considered an indication of biosimilar treatment failure or dissatisfaction with biosimilar treatment. Increasing our knowledge of patients who retransition might help to reduce the number of patients retransitioning. Objective Our objective was to estimate the cumulative incidence of patients who retransitioned from a tumor necrosis factor (TNF)-α inhibitor biosimilar to originator and to explore potential patient, disease, and treatment and implementation strategy factors associated with retransitioning. Method We conducted a systematic literature search in the PubMed, EMBASE, and Cochrane Central Register of controlled trials databases until March 2021. Studies on TNFα inhibitors, biosimilar transitioning, and retransitioning were included. Transitioning was defined as switching from an originator to a biosimilar, and retransitioning was defined as switching from an originator to a biosimilar and back to the originator. Characteristics of the studies were descriptively analyzed. Studies were weighted by the number of patients transitioning, and the primary outcome was the median cumulative incidence of retransitioning. For each of the factors related to patient, disease, and treatment and implementation strategy, studies were stratified according to the categories of that factor. The weighted medians and interquartile ranges (IQRs) of the cumulative incidence of retransitioning in these studies were calculated and compared to explore whether a potential association existed between these factors and the cumulative incidence of retransitioning. Results Of 994 screened publications, 37 were included. The weighted median cumulative incidence of retransitioning was 7.6% (IQR 6.8-17.2). Studies that included only patients with inflammatory bowel disease (6.6 vs. 15.1-17.7% for other indications), included only patients with stable disease (7.0 vs. 13.7% for including all patients), and did not offer retransitioning at the introduction of the biosimilar (7.0 vs. 11.1% for studies that offered retransitioning) reported less retransitioning. In addition, the incidence of retransitioning was lower when extra laboratory monitoring was part of the implementation strategy (1.6 vs. 6.1%) and when gainsharing (patients' healthcare directly benefits from financial savings from transitioning) (1.4 vs. 7.2% for studies without gainsharing) was applied. Conclusions In studies on transitioning patients from TNFα originator to biosimilar, 8% of patients retransitioned. Retransitioning appeared to be lower in studies that included only patients with stable disease and in studies that did not offer patients the option of retransitioning at...

TNF-alpha inhibitors biosimilar use in France: a nationwide population-based study using the French National Health Data System

“…We report in this study that retransition is not an isolated fact, with respectively 22%, 37% and 32% of infliximab, etanercept and adalimumab prevalent users retransitioning during the study follow-up. This is not consistent with a systematic review 14 that calculated lower retransition rates, with an average of 8% of retransitions among patients having previously transitioned from originator to biosimilar product a year after the first transition. Nocebo effect has already been suggested to explain biosimilar discontinuation 15,16 , while previous studies did not show any adverse events profiles in transitioning patients compared to non-transitioning patients [17][18][19] .…”

Discontinuation of infliximab treatment in patients with inflammatory bowel disease who retransitioned to originator and those who remained on biosimilar

“…In total, 24.7% of patients in our study who initially transitioned from originator to biosimilar subsequently retransitioned, which is much higher than the 7% reported in an earlier systematic review. 9 Studies included in the systematic review had a median follow-up of 12 months. However, as patients in our study retransitioned after a median of 8.6 (3.7–14.0) months, the long follow-up time of our study (median 3.6–years from transitioning) allowed for more patients to retransition, which shows that retransitioning might also occur after a longer period of time.…”

“…they stopped the biosimilar and reinitiated the originator). 9 Retransitioning is mainly due to either a perceived or objective increase in disease activity or the occurrence of (subjective) adverse events after transitioning to the biosimilar. 10 – 12 However, no clear pharmacotherapeutic rationale exists for retransitioning, and furthermore, it is not recommended in clinical guidelines.…”