Subcutaneous infliximab CT-P13 has demonstrated significant efficacy as a maintenance therapy for inflammatory bowel disease (IBD), according to results from two randomized, placebo-controlled Phase 3 trials (LIBERTY). The studies, published in Gastroenterology, evaluated the biosimilar in patients with Crohn's disease (CD) and ulcerative colitis (UC) who had previously responded to intravenous CT-P13 induction therapy.
The trials met their primary and key secondary endpoints, showing that subcutaneous CT-P13 was superior to placebo in maintaining clinical remission and endoscopic response. These findings suggest a potential new treatment option for patients seeking a more convenient administration route.
Efficacy in Crohn's Disease
The Crohn's disease study assessed clinical remission based on the Crohn's Disease Activity Index (CDAI) and endoscopic response at week 54. Results indicated that 62% of patients in the CT-P13 group achieved clinical remission compared to only 32% in the placebo group. Endoscopic response was also significantly higher in the CT-P13 group (51%) versus the placebo group (18%).
Efficacy in Ulcerative Colitis
In the ulcerative colitis study, the primary endpoint was clinical remission at week 54. The rate of clinical remission was 43% in the CT-P13 group compared to 21% in the placebo group. Key secondary endpoints, including clinical response and endoscopic-histologic mucosal improvement, were also significantly higher in the CT-P13 group.
Safety and Tolerability
Both studies reported that subcutaneous CT-P13 was well-tolerated, with a safety profile consistent with previous studies of intravenous and subcutaneous CT-P13. The most common treatment-emergent adverse event (TEAE) was COVID-19, followed by headache in the CD study and exacerbation of UC in the UC study. Injection-site reactions were slightly more frequent in the CT-P13 group, as expected, but no delayed hypersensitivity events were reported.
Impact of Anti-Drug Antibodies
Anti-drug antibodies (ADA) were detected in a significant proportion of patients in both treatment groups. In the CD study, 65% of patients in the CT-P13 group and 76% in the placebo group tested positive for ADAs. In the UC study, the rates were 64% and 92%, respectively. The investigators noted that clinical remission and endoscopic response rates tended to be slightly lower in ADA-positive patients compared to ADA-negative patients in the CD study, while rates were comparable in the UC study.
Clinical Implications
These findings support the use of subcutaneous CT-P13 as an effective and well-tolerated maintenance therapy for patients with Crohn's disease and ulcerative colitis who have responded to intravenous CT-P13 induction. The subcutaneous formulation offers a more convenient administration option, potentially improving patient adherence and quality of life. According to the investigators, these are the first placebo-controlled trials to evaluate subcutaneous CT-P13 as maintenance therapy in IBD.
