LIBERTY-UC: Maintenance subcutaneous infliximab eases moderate-to-severe UC
The subcutaneous (SC) infliximab formulation CT-P13 appears beneficial in the maintenance treatment of patients with moderately to severely active ulcerative colitis (UC), with data from the phase III study LIBERTY-UC showing that the drug outperforms placebo in multiple endpoints.
“Superiority was demonstrated for CT-P13 over placebo in patients who responded to intravenous (IV) induction with CT-P13 based on clinical remission, clinical response, endoscopic-histologic mucosal improvement, and corticosteroid-free remission at week 54,” according to one of the study authors Dr Bruce Sands of the Icahn School of Medicine at Mount Sinai in New York City, New York, US, who spoke at DDW 2023.
LIBERTY-UC included 548 UC patients with modified Mayo score of 5–9 and endoscopic subscore of ≥2 points. These patients were treated with open-label CT-P13 IV 5 mg/kg at weeks 0, 2 and 6 as induction therapy. At week 10, 438 patients (79.9 percent) responded to CT-P13 IV induction dosing and were subsequently randomly assigned to receive maintenance treatment with either CT-P13 SC 120 mg (n=294; median age 37 years, 55.4 percent men) or placebo (n=144; median age 39 years, 57.6 percent men) every 2 weeks up to week 54.
Clinical response was defined as a decrease in modified Mayo score of at least 2 points and at least 30 percent from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 point.
The rate of clinical remission at week 54, the primary endpoint, was 43.2 percent with CT-P13 SC vs 20.8 percent with placebo (p<0.0001). The corresponding rates for key secondary endpoints assessed at the same time point were as follows: 53.7 percent vs 31.3 percent for clinical response (p<0.0001), 35.7 percent vs 16.7 percent for endoscopic-histologic mucosal improvement (p<0.0001), and 36.7 percent vs 18.0 percent for corticosteroid-free remission (p=0.0127). [DDW 2023, abstract 1701]
“Trough concentration of CT-P13 SC were well sustained above the target therapeutic concentration level (5 µg/mL) up to week 54,” Sands noted.
Median concentrations of the inflammatory biomarkers C-reactive protein and faecal calprotectin were maintained at low level in the CT-P13 SC group and were consistently lower than in the placebo group, he added.
As for safety, the use of CT-P13 SC in the maintenance setting was well tolerated, with Sands pointing out a lack of clinically meaningful differences in the frequencies of treatment-emergent adverse events (TEAEs) between the investigational drug and placebo (67.6 percent and 59.3 percent, respectively).
The most common TEAE was infection, occurring in 28.0 percent of patients in the CT-P13 SC group and in 25.7 percent in the placebo group, followed by systemic injection reaction (4.1 percent and 2.9 percent, respectively) and localized injection site reaction (3.4 percent and 2.1 percent, respectively). TEAEs led to treatment discontinuation in 3.4 percent of patients on CT-P13 SC and in 2.9 percent of those on placebo. Serious adverse events were documented in 6.4 percent and 2.9 percent, respectively. No deaths were reported.
“CT-P13 subcutaneous (SC) infliximab formulation was developed to provide patients with a convenient option for treatment. Previous studies have shown efficacy and safety of CT-P13 SC comparable to CT-P13 IV in inflammatory bowel disease and rheumatoid arthritis,” Sands said. [Gastroenterology 2021;160:2340-2353; Rheumatology 2021;60:2277-2287]The results of LIBERTY-UC “demonstrate that the CT-P13 SC provides both a robust clinical benefit and the convenience of SC administration to patients with moderately to severely active UC,” he concluded.