One-year results after transitioning from etanercept originator to biosimilar in a setting promoting shared decision-making in rheumatology

Abstract

Objective Study the effect of non-mandatory transitioning from etanercept originator to etanercept biosimilar on retention rates in a shared decision making-promoting setting. Methods In 2016 all patients treated with etanercept originator and stable disease at the Rheumatology department in Bernhoven were offered transitioning to etanercept biosimilar by opt-in approach. A historical cohort of patients treated with etanercept originator in 2015 was identified as control group. Etanercept discontinuation was compared between the cohorts using Cox-regression. To study the nocebo-effect reasons for discontinuation were categorized into objective reasons (e.g., laboratory abnormalities, increase in swollen joint count, allergic reaction) and "subjective health complaints" (symptoms only perceptible to the patient, e.g., tiredness, arthralgia). An adjusted Kaplan-Meier curve for retention of the etanercept biosimilar was made, censoring subjective health complaints as reason for discontinuation. Results 70 of the 79 patients eligible for transitioning agreed to transition (89%). The one year crude retention rate of etanercept in the transition cohort was 73% (95% CI 0.62-0.83), compared to a retention rate of 89% (95% CI 0.81-0.95) in the historical cohort, p-value= 0.013. This resulted in a higher risk of treatment discontinuation in the transition cohort (adjusted hazard ratio=2.73; 95%CI 1.23-6.05, p-value= 0.01). After adjusting for the nocebo-effect, the cohorts had comparable retention rates (86% vs. 89%, p-value= 0.51). Conclusion Non-mandatory transition from etanercept originator to its biosimilar using an opt-in approach in a shared decision-making promoting setting resulted in a higher discontinuation of etanercept compared to the historical cohort. This could largely be attributed to the nocebo-effect.

Incidence of and Reasons and Determinants Associated with Retransitioning from Biosimilar Etanercept to Originator Etanercept

“…In the present study, the majority of patients (82.4%) continued to use biosimilar etanercept 6 months after transitioning from originator etanercept to biosimilar etanercept; this proportion decreased to 69.7% at 1 year after transitioning. Previous studies on transitioning to biosimilar etanercept in patients with RD, also performed in 2016, reported higher rates of persistence, varying from a 6-month persistence of 90% [8,13] to a 1-year persistence of 73-83% [7,10]. Political factors such as the availability of the originator, regional/ national policies, and pricing and reimbursement of the originator and the biosimilar are likely to affect the persistent use of the biosimilar and therefore the proportion of patients retransitioning.…”

“…Moreover, in the aforementioned observational studies and others, 2.7-17.2% of patients who transitioned from originator etanercept to the etanercept biosimilar retransitioned to originator etanercept within 6-12 months [7][8][9][10]. The most important reasons for retransitioning were adverse events caused by the etanercept biosimilar, including subjective adverse events such as arthralgia and fatigue, or (perceived) loss of effect.…”

Biologic Drugs for Rheumatoid Arthritis in the Context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment

“…Only proven similar efficacy and safety in short- and long-term trials allow switching between original drug and biosimilar [ 37 , 46 , 47 ]. However, such drug change was burdened with strong nocebo effect, thus lowering biosimilar’s efficacy [ 48 , 49 ].…”

Biosimilar Uptake: The Importance of Healthcare Provider Education

“…This effect is believed to be responsible for negative treatment outcomes that arise because of a patient's negative perceptions (or expectations) of the treatment and not because of the action of the treatment itself. The magnitude of this effect is not fully understood and could vary with disease state, but several recent studies on infliximab and etanercept biosimilars suggest an effect on the magnitude of 1 in 8 patients [26][27][28].…”