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

Geert D’Haens, Walter Reinisch, Stefan Schreiber, Fraser Cummings, Peter M. Irving, Byong Duk Ye, Dong Hyeon Kim, Sang Wook Yoon, Shomron Ben-Horin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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. Graphical Abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)277-288
Number of pages12
JournalClinical Drug Investigation
Volume43
Issue number4
DOIs
StatePublished - Apr 2023

Funding

FundersFunder number
Aspire Scientific Limited
Beatrice Tyrrell
Celltrion Healthcare Co., Ltd

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