Switching Back to Originator From Biosimilar Infliximab Results in Higher Discontinue Rates

Patients who went back to originator infliximab (Remicade) after switching a biosimilar were at greater risk of discontinuing treatment due to an unwanted response compared with patients who remained on the biosimilar, according to a study published in Therapeutic Advances in Gastroenterology.

While transitioning from the originator to a biosimilar has been proven safe and effective, it is not uncommon for patients to retransition to the originator product and discontinue use of the biosimilar.

The authors explained that there is “no clear pharmacotherapeutic rationale exists for retransitioning,” and that patients who regained efficacy or who saw adverse events (AEs) resolve after retransitioning to the originator product were likely experiencing the nocebo effect on the biosimilar.

The matched cohort study included 198 patients with at least 1 year of follow-up who had transitioned from the reference product to an infliximab biosimilar. The median total follow-up time was 3.6 years after transitioning.

The median age was 39.9 years, and the majority (53.0%) were female. One-fourth (24.7%) of patients retransitioned to the originator, which occurred a median (IQR) of 8.6 (3.7-14.0) months after the initial transition.

Patients who retransition from a biosimilar back to the originator product who regain efficacy or saw adverse events resolve as a result of switching back were likely experiencing the nocebo effect, the researchers write.

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After matching, there were 44 patients in the retransition cohort and 127 patients who remained on the biosimilar. More than half (58.4%) of patients had Crohn disease and 26.9% had ulcerative colitis, while 14.6% were listed as unknown due to an inability to retrieve disease information from the archives of an old electronic health record (EHR).

Patients who retransitioned tended to be younger (median, 39.9 vs 44.0 years) and were more likely to be female (65.9% vs 48.9%). Patients who retransitioned also had a shorter median dosing interval compared with the patients on a biosimilar (48.5 days vs 56 days).

The reasons given for retransition included loss of effect (36.4%), AE (29.5%), or both (22.7%). For 9% of patients, no reason for the retransition was listed in their EHR. Fatigue, skin complaints, and joint complaints were the most reported AEs.

Early on in the follow-up, 9.4% patients in the biosimilar cohort compared with none in the retransition cohort. However, by the end of the follow-up, 25.0% of patients in the retransition cohort had discontinued infliximab use compared with 22.8% of patients in the biosimilar cohort.

Patients in the retransition cohort were more likely to have discontinued due to unwanted response by the end of the follow up (22.7% vs 13.4%). Patients on the biosimilar were more likely to have discontinued due to remission (9.4%) vs 2.3%).

Half of the patients who retransitioned and discontinued switched to another biologic, while 17.6% of patients on a biosimilar switched to another biologic.

The 24.7% of patients who retransitioned is much higher than the 7% reported in an earlier study, the authors noted. However, this study had a much longer follow-up time, “which shows that retransitioning might also occur after a longer period of time,” they wrote.

The small number of patients in the study was one key limitation, and this small number meant they could not perform subgroup analyses. However, the main drivers for retransitioning were patient-related, which means the study results could be generalizable to other indications and biosimilars.

“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,” the authors concluded. “Clinicians could consider patients who opt for retransitioning to another treatment option.”

Reference

Meijboom RW, Gardarsdottir H, Becker ML, Movig KLL, 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. doi:10.1177/17562848231197923