Discontinuation of Infliximab Treatment in IBD Patients: A Comparison Between Patients Who Retransitioned to Originator and Those Who Remained on Biosimilar

Background: Many patients in clinical care with inflammatory bowel disease (IBD) transitioned from infliximab originator to a biosimilar. Studies demonstrate that on average 7% of patients who transition to biosimilar, retransition to infliximab originator (i.e. stop biosimilar, reinitiate originator), mainly due to (perceived) loss of effect or adverse events. Whether this unsatisfactory treatment response is related to the product or to the patient and his/her disease is unclear.

Objectives: To compare the risk of infliximab discontinuation between patients who retransition to originator and those who remain on biosimilar.

Methods: IBD patients who transitioned from infliximab originator to biosimilar between January 2015 and September 2019 were eligible for inclusion. Patients who retransitioned to infliximab originator (index date) were included in the retransitioning cohort and matched with up to 3 patients who remained on biosimilar (biosimilar remainder cohort). Patients were matched on: hospital, transitioning date and duration of biosimilar treatment up to index date.

Patients were followed from index date until discontinuation of infliximab (>16 weeks no administration, or switch to another biological). Risk of infliximab discontinuation (overall discontinuation, switching to another biological or discontinuation without switching) was compared using a conditional Cox proportional hazards model, adjusted for age, gender, duration of infliximab originator use prior to transitioning and the number of other biologicals used before infliximab.

Results: Baseline characteristics of the retransitioning cohort (n=42, 59.9% females, median age 45.0 years ) and the biosimilar remainder cohort (n=120,55.0% females, median age 43.0 years ) were similar, but dosing interval was shorter in the retransitioning cohort (44 versus 56 days). Infliximab treatment discontinuation after 12 months was 25.0% in the retransitioning cohort and 8.8% in the biosimilar remainder cohort. Retransitioned patients had a twofold increased risk of discontinuing infliximab (adjusted HR 2.2, 95% CI 1.1-4.3) compared with patients remaining on biosimilar. The risk of switching (adjusted HR 8.1, 95%CI 0.9-71.1) was higher than that of discontinuing without switching (adjusted HR 1.7, 95%CI 0.8-3.8).

Conclusions: Retransitioned patients have a twofold increased risk for infliximab discontinuation, including both switching to another biological or discontinuing without switching. Our results indicate that retransitioning is mainly patient or disease related and less likely to be product related.