TY - JOUR
T1 - Subcutaneous Infliximab Monotherapy Versus Combination Therapy with Immunosuppressants in Inflammatory Bowel Disease
T2 - A Post Hoc Analysis of a Randomised Clinical Trial
AU - D’Haens, Geert
AU - Reinisch, Walter
AU - Schreiber, Stefan
AU - Cummings, Fraser
AU - Irving, Peter M.
AU - Ye, Byong Duk
AU - Kim, Dong-Hyeon
AU - Yoon, SangWook
AU - Ben-Horin, Shomron
N1 - Funding Information: Medical writing support, including development of article drafts in consultation with the authors, collating author comments, copyediting, fact checking, and referencing, was provided by Beatrice Tyrrell, DPhil, CMPP, at Aspire Scientific Limited (Bollington, UK). Funding Information: This post hoc analysis was funded in full by Celltrion Healthcare Co., Ltd (Incheon, Republic of Korea). Medical writing support for this article was funded by Celltrion Healthcare Co., Ltd. Open access funding was provided by Celltrion Healthcare Co., Ltd. Publisher Copyright: © 2023, The Author(s).
PY - 2023/4
Y1 - 2023/4
N2 - 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.]
AB - 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.]
UR - http://www.scopus.com/inward/record.url?scp=85151457824&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s40261-023-01252-z
DO - https://doi.org/10.1007/s40261-023-01252-z
M3 - Article
C2 - 37004656
SN - 1173-2563
VL - 43
SP - 277
EP - 288
JO - Clinical drug investigation
JF - Clinical drug investigation
IS - 4
ER -