Study Details Trends in Retransition, Discontinuation of Infliximab Biosimilars

Thijs Giezen, PharmD, PhD, MSc

Credit: Biosimilars Nederland

Patients with inflammatory bowel disease who retransition to an infliximab originator after switching to a biosimilar are at an increased risk of infliximab discontinuation, according to findings from a recent matched cohort study.

Among those who retransitioned to originator infliximab during the follow-up, 25% discontinued infliximab compared to 22.8% among those who remained on biosimilar infliximab.¹

“Despite the fact that many patients in clinical practice successfully transitioned from infliximab originator to biosimilar, studies have demonstrated that on average 7% of patients with IBD who transitioned subsequently retransitioned to originator infliximab,” wrote investigators.¹

The US Centers for Disease Control and Prevention lists 5-aminosalicyclic acids, immunomodulators, corticosteroids, and biologics as common medications for the treatment of inflammatory bowel disease.² In recent years, biosimilars have gained attention as an alternative to biologic medication. In the US, the first infliximab biosimilar to receive approval was Inflectra, which received approval from the US FDA in April 2016.³

To compare the risk of and reasons for infliximab discontinuation between retransitioned patients and those remaining on biosimilar, Thijs Giezen, PharmD, PhD, MSc, hospital pharmacist at the Foundation Pharmacy for Hospitals in the Netherlands, and a team of investigators matched retransitioned patients with patients remaining on biosimilar at 2 hospitals, Spaarne Gasthuis and Medisch Spectrum Twente, in the Netherlands. Matching criteria included treatment in the same hospital, transition date in the same 6-month calendar period, and duration of biosimilar use from transition date.¹

Investigators followed patients from their index date until discontinuation of biological treatment, censoring, death, loss of follow-up, or the end of data collection. The primary outcome of interest was infliximab treatment discontinuation, defined as not receiving an infliximab administration within 16 weeks after the date of the last administration.¹

Reasons for discontinuation were categorized as unwanted response or remission. Investigators assessed age, gender, duration of use of infliximab originator prior to transitioning, and the number of other biologicals used before initiating treatment with infliximab as potential confounders.¹

In total, 198 patients transitioned from infliximab originator to the biosimilar. These patients had a median age of 39.9 years and 53.0% were female. Of these patients, 49 (24.7%) retransitioned to originator infliximab during follow-up. Retransitioning occurred after a median of 8.6 months (interquartile range [IQR], 3.7–14.0) after transitioning. The main reasons for retransition were loss of effect (36.4%), adverse events (29.5%), or both loss of effect and adverse events (22.7%).¹

After matching, there were 44 patients in the retransitioning cohort and 127 patients in the biosimilar remainder cohort. Investigators noted patients in the retransitioning cohort were younger (median 39.9 years vs 44.0 years), were more often female (65.9% vs 48.9%), and had a shorter median dosing interval (48.5 days; IQR, 42–56 days vs 56 days; IQR, 45–56) than patients in the biosimilar remainder cohort.¹

After 6 months of treatment, none of the patients in the retransitioning cohort discontinued infliximab treatment compared to 9.4% of patients in the biosimilar remainder cohort. Discontinued infliximab treatment increased to 9.1% in the retransitioning cohort and 11.8% in the biosimilar remainder cohort after 1 year. By the end of the follow-up, rate of discontinuation reached 25.0% and 22.8% of the retransitioning and biosimilar remainder cohorts, respectively.¹

Within the subgroup of patients who discontinued infliximab treatment, patients in the biosimilar remainder cohort discontinued more often due to remission (41.4%) than patients in the retransitioning cohort (9.1%). Patients who retransitioned discontinued infliximab treatment more often due to unwanted response compared to patients who remained on biosimilar (22.7% vs 13.4%, respectively).¹

Of the 44 retransitioned patients, 6 mentioned changes in objective disease markers as the reason for retransitioning. Among the other 38, only symptoms were mentioned. Investigators noted infliximab continuation rates were higher in the patients who retransitioned due to symptoms only (76.3%) compared to patients who retransitioned based on objective disease markers (33.3%).¹

In both the unadjusted and adjusted Cox proportional hazard models up to 11.2 months of follow-up, patients in the retransitioning cohort had a similar risk of overall infliximab discontinuation due to an unwanted response compared to patients in the biosimilar remainder cohort (hazard ratio [HR], 1.1; 95% CI, 0.3–4.3; adjusted hazard ratio [aHR], 1.0; 95% CI, 0.3–4.2). After 11.2 months, patients in the retransitioning cohort were at increased risk for overall infliximab discontinuation (HR, 2.1; 95% CI, 0.7–6.2; aHR, 3.7; 95% CI: 1.0–13.9).¹

“These findings indicate that retransitioning is mainly related to the patient and/or his/her disease including patients’ beliefs on the biosimilar and less likely related to the infliximab biosimilar itself. Clinicians could consider patients who opt for retransitioning to another treatment option,” investigators concluded.¹

References

1. Meijboom RW, Gardarsdottir H, Becker ML, et al. Discontinuation of infliximab treatment in patients with inflammatory bowel disease who retransitioned to originator and those who remained on biosimilar. Therap Adv Gastroenterol. 2023;16:17562848231197923. Published 2023 Sep 11. doi:10.1177/17562848231197923
2. Centers for Disease Control and Prevention. What is inflammatory bowel disease (IBD)? Inflammatory bowel disease (IBD). Accessed September 19, 2023. https://www.cdc.gov/ibd/what-is-IBD.htm
3. U.S. Food & Drug Administration. FDA approves Inflectra, a biosimilar to Remicade. Press Announcements. April 5, 2016. Accessed September 19, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-inflectra-biosimilar-remicade