The efficacy of maintenance with a modified biosimilar of infliximab in promoting healing of inflamed mucosa in Crohn’s disease (CD) is observed along all intestinal segments assessed during colonoscopy, a post hoc analysis of the LIBERTY-CD trial has shown.

In patients who had endoscopic abnormalities in any of the five evaluated ileocolonic segments (rectum, left colon, transverse colon, right colon, and terminal ileum) at screening, those randomized to receive infliximab biosimilar in a subcutaneous (SC) formulation as maintenance treatment had higher rates of endoscopic healing (EH) upon re-evaluation at week 54 vs those who received placebo maintenance (p≤0.01 across all five segments).

EH was defined as a Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) of zero.

“SC infliximab 120 mg Q2W led to high and consistent endoscopic mucosal healing rates across all segments, including the terminal ileum,” said lead author Professor Bruce Sands from the Icahn School of Medicine at Mount Sinai, New York City, New York, US, at AIBD 2024.

Clinical trial findings have established that endoscopic improvement is less readily achieved in ileal inflammation in CD following biological treatments. [Nat Rev Gastroenterol Hepatol 2021;18:544-558] In the current analysis, a higher proportion of patients treated with SC infliximab achieved EH in the terminal ileum than those treated with placebo (56.8 percent vs 23.3 percent; p<0.01). [AIBD 2024, abstract S49]

IV induction followed by SC maintenance

CT-P13 was the infliximab biosimilar employed in LIBERTY-CD, with both its IV and SC formulations selected as study treatments.

The phase III trial consisted of a 6-week open-label induction phase, during which all enrolled patients (n=396) received an IV infusion of CT-P13 at weeks 0, 2, and 6. Clinical responders to CT-P13 IV at week 10 were then randomized 2:1 to receive maintenance treatment with either CT-P13 SC 120 mg (n=231) or placebo (n=112) Q2W. [Gastroenterology 2024;167:919-933]

The Q2W injection intervals (vs IV infusion of ≥1 hour Q8W with originator infliximab or other infliximab biosimilars) were derived from pharmacokinetic models to provide consistent drug levels.

From week 22 onwards, treatment escalation to CT-P13 SC 240 mg Q2W was permitted for patients in either arm who lost their response, albeit being considered nonresponders in the analysis.

At screening, the left colon was the most frequently affected segment (54.5 percent), followed by the right colon (53.9 percent), rectum (47.5 percent), terminal ileum (45.5 percent), and transverse colon (39.1 percent).

The five evaluated segments corresponded to how the bowel is divided to calculate the total SES-CD.

Endoscopic response

Endoscopic response (ER) was another outcome derived from centrally reviewed endoscopies, defined as ≥50 percent decrease in the SES-CD from the score at screening.

At week 54, patients maintained on SC infliximab achieved significantly higher ER rates across all segments than those on placebo (all p≤0.01).

Week 54 also saw a higher proportion of patients on SC infliximab vs placebo having an ER in the terminal ileum (69.3 percent vs 30.2 percent; p<0.001).

Among patients in the SC infliximab maintenance arm, the rate of ER in the terminal ileum was higher in those with a disease duration of <2 years vs ≥2 years (85.1 percent vs 65 percent; p=0.0435).

“Early treatment with SC infliximab may lead to higher rates of ER in patients with active ileal lesions,” concluded Sands.