Clin Drug Investig. 2023 Apr;43(4):277-288.doi: 10.1007/s40261-023-01252-z. Epub 2023 Apr 1

Geert D'Haens ¹, Walter Reinisch ², Stefan Schreiber ³, Fraser Cummings ⁴, Peter M Irving ^5 6, Byong Duk Ye ⁷, Dong-Hyeon Kim ⁸, SangWook Yoon ⁸, Shomron Ben-Horin ⁹

Author information

¹Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

²Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.

³Department for Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.

⁴Department of Gastroenterology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

⁵Department of Gastroenterology, Guy's and St Thomas' Hospital, London, UK.

⁶School of Immunology and Microbial Sciences, King's College London, London, UK.

⁷Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

⁸Medical Department, Celltrion Healthcare Co., Ltd, Incheon, Republic of Korea.

⁹Gastroenterology Department, Chaim Sheba Medical Center, Tel Aviv University, Ramat Gan, Tel-Hashomer, Israel. shomron.benhorin@gmail.com.

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.