Subcutaneous Infliximab Monotherapy Versus Combination Therapy with Immunosuppressants in Inflammatory Bowel Disease: A Post Hoc Analysis of a Randomised Clinical Trial.

Abstract

BACKGROUND AND OBJECTIVE:

Whether benefits and risks of intravenous (IV) infliximab combotherapy with immunosuppressants versus infliximab monotherapy apply to subcutaneous (SC) infliximab is unknown. This post hoc analysis of a pivotal randomised CT-P13 SC 1.6 trial aimed to compare SC infliximab monotherapy with combotherapy in inflammatory bowel disease (IBD).

METHODS:

Biologic-naïve patients with active Crohn's disease or ulcerative colitis received CT-P13 IV 5 mg/kg at Week (W) 0 and 2 (dose-loading phase). At W6, patients were randomised (1:1) to receive CT-P13 SC 120 or 240 mg (patients < 80 or ≥ 80 kg) every 2 weeks until W54 (maintenance phase), or to continue CT-P13 IV every 8 weeks until switching to CT-P13 SC from W30. The primary endpoint-non-inferiority of trough serum concentrations-was assessed at W22. We report a post hoc analysis comparing pharmacokinetic, efficacy, safety and immunogenicity outcomes up to W54 for patients randomised to CT-P13 SC, stratified by concomitant immunosuppressant use.

RESULTS:

Sixty-six patients were randomised to CT-P13 SC (37 monotherapy, 29 combotherapy). At W54, there were no significant differences in the proportions of patients achieving target exposure (5 µg/mL; 96.6% monotherapy vs 95.8% combotherapy; p > 0.999) or meeting efficacy or biomarker outcomes including clinical remission (62.9% vs 74.1%; p = 0.418). Monotherapy and combotherapy groups had comparable immunogenicity (anti-drug antibodies [ADAs]: 65.5% vs 48.0% [p = 0.271], neutralising antibodies [in ADA-positive patients]: 10.5% vs 16.7% [p = 0.630], respectively).

CONCLUSIONS:

Pharmacokinetics, efficacy and immunogenicity were potentially comparable between SC infliximab monotherapy and combotherapy in biologic-naïve IBD patients.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT02883452.

• Authors: Geert D'Haens, Walter Reinisch, Stefan Schreiber, Fraser Cummings, Peter M Irving, Byong Duk Ye, Dong-Hyeon Kim, SangWook Yoon, Shomron Ben-Horin
• Journal: Clinical drug investigation (Clin Drug Investig) Vol. 43 Issue 4 Pg. 277-288 (Apr 2023) ISSN: 1179-1918 [Electronic] New Zealand
• PMID: 37004656 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Infliximab
• Immunosuppressive Agents
• Biosimilar Pharmaceuticals
• Gastrointestinal Agents

Topics

• Humans
• Infliximab (adverse effects)
• Immunosuppressive Agents (adverse effects)
• Treatment Outcome
• Biosimilar Pharmaceuticals (therapeutic use)
• Inflammatory Bowel Diseases (drug therapy, chemically induced)
• Gastrointestinal Agents (adverse effects)