Subcutaneous Infliximab CT-P13 Superior to Placebo as Maintenance Therapy for IBD

In 2 randomized controlled trials of maintenance therapy for inflammatory bowel disease (IBD), the subcutaneous formulation of the infliximab biosimilar CT-P13 demonstrated superiority to placebo in patients with Crohn disease (CD) and ulcerative colitis (UC). Both studies met primary and key secondary endpoints, and there were no new safety signals.

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Tumor necrosis factor (TNF)-α is central to the pathology of IBD, chronic inflammatory diseases of the gastrointestinal tract. Infliximab was the first anti-TNF therapy approved for IBD, and the intravenous formulation of CT-P13 (Celltrion; Inflectra and Remsima) was the first approved infliximab biosimilar. A subcutaneous formulation of CT-P13 (Zymfentra and Remsima SC) was developed as a more convenient option for patients, allowing home self-administration. Subcutaneous CT-P13 was approved by the European Medicines Agency for IBD in 2020. According to the investigators, the subcutaneous formulation “creates a unique exposure profile,” and as a result, the FDA approved CT-P13 as a new drug in 2023.

The LIBERTY studies randomized clinical responders to intravenous CT-P13 to subcutaneous CT-P13 or placebo for maintenance therapy in CD and UC following a 10-week open-label induction phase in which all patients received intravenous CT-P13.

In the CD study, co-primary endpoints were clinical remission based on Crohn disease activity index (CDAI) and endoscopic response at week 54, and in the UC study the primary endpoint was clinical remission at week 54. In the CD study, a significantly higher proportion of patients in the CT-P13 group compared to the placebo group achieved clinical remission (62% vs 32%) and endoscopic response (51% vs 18%), the co-primary endpoints.

In the UC study, the rate of clinical remission was also significantly higher among patients receiving CT-P13 compared to placebo (43% vs 21%). In both studies, a significantly higher proportion of patients achieved key secondary efficacy endpoints in the CT-P13 group than the placebo group, including a 100-point or more decrease in CDAI, clinical remission by abdominal pain and stool frequency, and endoscopic remission in the CD study, clinical response and endoscopic-histologic mucosal improvement in the UC study, and corticosteroid-free remission in both studies.

Subcutaneous infliximab CT-P13 was well-tolerated, and there were no safety findings new to intravenous or subcutaneous CT-P13, the authors said. During the maintenance phase of the study, 72% and 62% of patients in the CD and UC studies experienced one or more treatment-emergent adverse events (TEAEs). The most common TEAE was COVID-19, followed by headache in the CD study and exacerbation of UC in the UC study. The number of patients who experienced adverse events of special interest was “generally low in both groups.”Injection-site reactions were “slightly higher” in the CT-P13 group compared to the placebo group, which the authors said was expected, and there were no delayed hypersensitivity events.

Antidrug antibodies (ADA) were detected in 65% of patients in the CT-P13 group and 76% of patients in the placebo group in the CD study, and 64% and 92% in the UC study. The proportion of patients positive for ADAs achieving clinical remission and endoscopic response “trended slightly lower” at week 54 than ADA-negative patients in the CD study and were comparable in the UC study.

The investigators concluded subcutaneous CT-P13 was more effective than placebo as maintenance therapy in patients with CD and UC who responded to CT-P13 induction and was well-tolerated. They added that their studies are the first placebo-controlled trials to evaluate subcutaneous CT-P13 as maintenance therapy in IBD.

Reference

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 (LIBERTY). Gastroenterology. 2024;167(5):919-933. doi:10.1053/j.gastro.2024.05.006