Study: Multiple Switches Between Infliximab Products May Lead to Higher Rates of Treatment Discontinuation

Patients with inflammatory bowel disease (IBD) who underwent multiple switches between infliximab products (originator to biosimilar to originator) were more likely to discontinue their treatment compared with patients who only switched once, according to a study published in Therapeutic Advances in Gastroenterology.

Inflammatory bowel disease (IBD) is an umbrella term for Crohn disease and ulcerative colitis, which are both characterized by chronic inflammation of the gastrointestinal tract.

Transitioning between reference agents and biosimilars has proven to be safe and effective in double-blind studies, including the NOR-SWITCH study, which assessed patients with IBD who transitioned once between Remicade (reference infliximab) and a biosimilar version. However, this study and others like it have found that, on average, 7% of the patients retransition back to Remcade, likely due to either an observed increase in disease activity or the occurrence of adverse events after transitioning to the biosimilar.

Alas, there is no clear pharmacotherapeutic reason for retransition, and it is not recommended in clinical guidelines. The authors noted that a resolution of adverse events or reduced efficacy after retransitioning to the originator could indicate that the patient experienced the nocebo effect, which occurs when patients negative perceptions about a medication result in negative clinical outcomes after experiencing a nonmedical switch between clinically equivalent therapies. Retransitioning can also be caused by a general lack in confidence in biosimilars by providers as well as patients; thus, it’s still unclear whether retransitioning is related to the drug itself or to the patients and their disease.

The analysis aimed to compare the risk of and reasons for treatment discontinuation between patients with IBD who remained on a biosimilar and those who retransitioned to the originator.

In the present analysis, the researchers collected data from 2 large teaching hospitals in the Netherlands. Patients with IBD who transitioned from Remicade to an infliximab biosimilar between January 2015 and September 2019 were eligible for enrollment.

Overall, 171 patients were included in the analysis, and 24.7% of the patients retransitioned to the originator, which is much higher than the 7% reported in previous reviews. Those who were retransitioned to the originator (n = 44) were matched with patients remaining on the biosimilar (n = 127). The median time from first transition to retransition was 8.6 months (range, 3.7-14.0).

The retransitioning cohort included more women (65.9% vs 48.9%) and had shorter dosing intervals (median, 48.5 vs 56.0 days) compared with the biosimilar remainder cohort. Discontinuation due to an unwanted response occurred in 22.7% of the retransitioning cohort and 13.4% of the biosimilar remainder cohort. Treatment discontinuation was attributed to remission 2.3% and 9.4% of the time in the retransitioning and biosimilar remainder cohorts, respectively.

Patients who retransitioned after 11.2 months of treatment had over a 3-fold increased risk for discontinuing infliximab due to unwanted response compared with patients who remained on the biosimilar (adjusted HR, 3.7; 95% CI, 1.0-13.9). Additionally, patients who retransitioned due to an increase in objective disease markers experienced higher discontinuation rates than patients who retransitioned due to a change in disease symptoms only (66.7% vs 23.7%).

The authors noted that because the route of administration and excipients between Remicade and the infliximab biosimilars used for the study are identical, the risk a discontinuation occurring because of allergy or difficulties with administration devices is low.

“As patients do not seem to benefit from retransitioning, clinicians might – after a thorough investigation to confirm active disease – consider switching patients who opt for retransitioning to another treatment regimen. However, in clinical practice, classifying certain subjective complaints, for example, joint pains, as an adverse event or as a nocebo effect can be difficult as these are often not objectively measurable,” the authors recommended.

The study had some limitations, including the small cohort sizes, lack of subgroup analyses by indication (Crohn disease vs ulcerative colitis), lack of data on disease activity, and some missing data from the hospitals’ new electronic health record.

The authors said that despite only including patients with IBD, they believed that since the nocebo and attribution effects, which are patient-related instead of indication-related, were the main drivers of retransitioning, their results should be generalizable to other indications. “Furthermore, biosimilars for other biologicals for long-term use are and will become available. We believe that the results from this study will be applicable to those biosimilars as well.”

Reference

Meijboom RW, Garsardottir 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. Published online September 11, 2023. doi:10.1177/17562848231197923