Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease.

Abstract

BACKGROUND & AIMS:

This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD).

METHODS:

This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore ≥2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (Ctrough,W22), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%.

RESULTS:

Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for Ctrough,W22 of 1154.17% (90% CI 786.37-1694.00; n = 59 [CT-P13 SC]; n = 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy, safety, and immunogenicity assessments were also broadly comparable between arms, including after switching.

CONCLUSIONS:

The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles, support the potential suitability of CT-P13 SC treatment in IBD. ClinicalTrials.gov ID: NCT02883452.

• Authors: Stefan Schreiber, Shomron Ben-Horin, Jaroslaw Leszczyszyn, Robert Dudkowiak, Adi Lahat, Beata Gawdis-Wojnarska, Aldis Pukitis, Marek Horynski, Katalin Farkas, Jaroslaw Kierkus, Maciej Kowalski, Sang Joon Lee, Sung Hyun Kim, Jee Hye Suh, Mi Rim Kim, Seul Gi Lee, Byong Duk Ye, Walter Reinisch
• Journal: Gastroenterology (Gastroenterology) Vol. 160 Issue 7 Pg. 2340-2353 (06 2021) ISSN: 1528-0012 [Electronic] United States
• PMID: 33676969 (Publication Type: Clinical Trial, Phase I, Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Biosimilar Pharmaceuticals
• CT-P13
• Gastrointestinal Agents
• Leukocyte L1 Antigen Complex
• C-Reactive Protein
• Infliximab

Topics

• Administration, Intravenous
• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage)
• Biosimilar Pharmaceuticals (administration & dosage)
• C-Reactive Protein (drug effects)
• Colitis, Ulcerative (drug therapy, metabolism)
• Crohn Disease (drug therapy, metabolism)
• Drug Substitution
• Feces (chemistry)
• Female
• Gastrointestinal Agents (administration & dosage)
• Humans
• Infliximab (administration & dosage, blood)
• Injections, Subcutaneous
• Leukocyte L1 Antigen Complex (drug effects)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Severity of Illness Index
• Treatment Outcome
• Young Adult