Infliximab Biosimilar CT-P13 Superior to Placebo for IBD Maintenance

Stephen B Hanauer, MD

Credit: Northwestern Medicine

A subcutaneous (SC) injection of infliximab biosimilar CT-P13 was proven to be a more effective maintenance therapy than placebo in patients with moderate to severe active Crohn’s disease or ulcerative colitis who initially responded to CT-P13 intravenous (IV) induction, according to a study published in Gastroenterology.¹

Investigators noted patients and providers often prefer a SC route over IV treatment for inflammatory bowel disease (IBD) as the self-administration strategy is a more convenient and flexible approach to management, exposure to nosocomial infection is reduced, and there is a different exposure profile with high steady-state levels. Given these advantages, the SC formulation of CT-P13 was introduced and approved by the European Medicines Agency (EMA) in 2019 and the US Food and Drug Administration (FDA) in 2023.²

Two randomized, placebo-controlled, double-blind, multicenter, parallel-group phase 3 studies enrolled patients with active, moderate to severe Crohn’s disease or ulcerative colitis who had inadequate response or intolerance to corticosteroids and immunomodulators.

At week 0, 2, and 6, all patients received open-label CT-P13 IV 5 mg/kg. At week 10, clinical responders were randomized 2:1 to receive either CT-P13 SC 120 mg or placebo every 2 weeks until week 54. The primary endpoints were clinical remission (per modified Mayo score) for the ulcerative colitis group and clinical remission (absolute Crohn’s Disease Activity Index [CDAI] score of <150 points) and endoscopic response (≥50% decrease in Simplified Endoscopic Activity Score for Crohn’s Disease [SES-CD] score from baseline) for the Crohn’s disease group at the end of the maintenance phase (week 54).

“These trials provide not only an assessment of the efficacy and safety of a novel exposure profile with infliximab in IBD but also benchmark the efficacy of CTP13 SC using endpoints incorporated into the pivotal program of IBD since the initial approvals of infliximab,” wrote a team of investigators led by Stephen B Hanauer, MD, professor in the Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Feinberg School of Medicine.

In total, 396 patients with Crohn’s disease and 548 patients with ulcerative colitis received induction treatment. In the Crohn’s disease study, statistically significant higher proportions of patients receiving CT-P13 SC achieved clinical remission (62.3% vs 32.1%, respectively; P <.0001) and endoscopic response (51.1% vs 17.9%, respectively; P <.0001). In the ulcerative colitis study, remission rates at the end of week 54 were statistically significant in the CT-P13 SC group compared with placebo (43.2% vs 20.8%, respectively; P <.0001).

Key secondary endpoint achievement was also significantly higher in those receiving CT-P13 SC compared with placebo in both studies. These included CDAI-100 response and endoscopic remission in the Crohn’s disease trial, and clinical response plus endoscopic-histologic mucosal improvement and corticosteroid-free remission in the ulcerative colitis trial.

The biosimilar was well-tolerated and no new safety signals were identified. The most common treatment-emergent adverse event (TEAE) during the maintenance phase for those receiving the biosimilar was COVID-19. In the placebo group, the most common TEAE was aggravation of the patient’s Crohn’s disease or ulcerative colitis.

Investigators mentioned the lack of a direct comparison between CT-P13 SC and CT-P13 IV as maintenance therapy may have limited the study, although previous research has evaluated this. Additionally, both trials enrolled patients with prior immunomodulatory use and allowed patients to receive concomitant immunomodulatory agents. Therefore, the results may not be generalizable to those with a differing treatment history, such as immunomodulatory-naïve patients.

“The findings confirm that CT-P13 SC is well tolerated in this population, with no clinically meaningful 32 differences in safety profile compared with placebo,” investigators concluded. “Overall, the results support CT-P13 SC as a treatment option for maintenance therapy in patients with IBD.”

References

1. ^{Hanauer SB, Sands BE, Schreiber S, et al. Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials. Gastroenterology. Published online May 22, 2024. doi:10.1053/j.gastro.2024.05.006}
2. ^{Alten R, An Y, Kim DH, et al. Re-routing infliximab therapy: subcutaneous infliximab opens a path towards greater convenience and clinical benefit. Clin Drug Investig 2022;42:477–489.}