Australian Patients With IBD Switched to Biosimilar Infliximab Maintain Long-Term Persistence

Data from the Australian real-world SAME study of nonmedical switching from the infliximab reference product to biosimilar CT‐P13 (Inflectra; Celltrion) found long-term persistence was similar between patients in the switched and non-switched cohorts after 4 years of follow-up. The investigators said the results “provide further reassurance that nonmedical switching is safe and clinically comparable to ongoing originator infliximab in clinically stable patients with IBD.”

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The SAME study had previously shown nonmedical switching to the infliximab biosimilar CT‐P13 from the originator was safe and noninferior compared to continuing the reference product in patients with inflammatory bowel disease (IBD).

Although several studies have reported cost savings associated with switching to infliximab, and several countries and regions require new prescriptions of anti-tumor necrosis factor biologics to be biosimilars, Australia does not mandate prescribing biosimilars, “and a significant portion of [IBD] patients may remain on originator infliximab owing to clinician and patient reluctance to switch.”

Randomized controlled trials and real-world studies have found infliximab biosimilars are safe and effective in IBD, for both infliximab-naive and switched patients. However, longer-term outcomes “remain less well described,” the authors said. Furthermore, they added, since some studies have suggested switching may negatively affect long-term clinical outcomes due to the nocebo effect, there is a need for longer-term studies.

The prospective parallel cohort noninferiority study enrolled 345 patients with IBD in steroid-free clinical remission across multiple centers in Australia on the originator infliximab. Patients either continued treatment with the originator (n = 141) or switched to CT‐P13(n = 204). Independent of the study, 4 hospitals had decided to switch all stable patients to the biosimilar, while 3 had decided to continue to use the originator.

At 48 weeks, treatment persistence, the primary outcome, was 92% among patients in the biosimilar group, and 94% in the originator group. Among patients who did not change from their initial treatment (n = 297) during follow-up, there was no difference in the risk of disease worsening between groups (HR, 1.08; 95% CI, 0.68-1.72).

Trough drug levels were not different between switch and non-switch over time or at any single time period throughout the follow-up. However, the authors did find that patients who were receiving dose escalation prior to the start of the study had lower drug levels than those who weren’t. Also, dose escalation of more than 5 mg/kg every 8 weeks was significantly associated with disease worsening (HR, 1.89; 95% CI, 1.13-3.17).

Rates of antidrug antibodies (ADAs) were similar between groups. Develoment of ADAs occurred in 5 patients in the switch group and 4 who remained on the originator. Overall rates of ADAs were similar between groups, at 10% in the switch group and 11% in the reference product group. The authors added that all patients who developed “clinically significant” antibodies had a change in drug therapy sometime during follow-up.

At least 1 adverse event (AE) occurred in 49% of patients in the biosimilar group and 53% of the reference product group, with no significant difference between groups. The authors said most AEs were mild and did not affect treatment persistence. In the biosimilar group, 25 patients (12%) experienced an AE leading to discontinuation of infliximab treatment, as well as 15 (11%) of patients in the reference product group. AEs leading to discontinuation included infection, vasculitis, drug‐induced lupus, and one death, which was associated with a pre‐existing malignancy.

Rates of infliximab discontinuation were also not significantly different between groups, occurring 35% in the switched group and 38% of those who stayed on the reference product (HR, 0.87; 95% CI, 0.59-1.28). One patient switched back to the originator, after a change in symptoms without objective evidence of inflammation.

Reasons for discontinuation included disease worsening (22% of those who discontinued the biosimilar and 24% of those who discontinued the reference product), dose escalation (35% and 32%), antibody development (5% and 11%), and infliximab‐related adverse events (8% and 8%), and were comparable between groups. Regardless of group, patients with UC had a higher likelihood of treatment discontinuation than those with CD.

According to the authors, this is the longest real-world study to compare switched and non-switched groups of patients with IBD on infliximab. The authors concluded their findings “provide reassurance to clinicians, patients, and healthcare payers, alike, regarding the long‐term safety, clinical effectiveness, and pharmacokinetic profile of nonmedical switching.”

Reference

Suo P, Srinivasan A, Thin L, et al. Comparing long-term infliximab persistence following a switch to a biosimilar in patients with inflammatory bowel disease: no cause for concern. J Gastroenterol Hepatol. 2025;40(5):1174-1181. doi:10.1111/jgh.16916