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a hepatologie

Gastroenterology and Hepatology

Gastroent Hepatol 2023; 77(5): 419–426. doi: 10.48095/ccgh2023419.

Subcutaneous infliximab in the treatment of refractory Crohn‘s disease patients – a pilot study of drug immunogenicity

Karin Černá 1, Dana Ďuricová1, Martin Lukáš1, Naděžda Machková1, Veronika Hrubá1, Kristýna Kaštylová1, Katarína Mitrová1, Marta Kostrejová1, Kristýna Kubíčková1, Štěpán Peterka1, Martin Kolář1, Jakub Jirsa1, Gabriela Vojtěchová1, Milan Lukáš1

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Introduction: Despite infliximab (IFX) still being the “gold standard” of biological therapy for Crohn’s disease (CD), its effectiveness may vary depending on many factors. One of these factors is the individual patient’s reaction to the drug. A significant clinical problem is the immunogenicity of IFX, where up to 60% of treated patients may develop antibodies against the drug, leading to a loss of response to treatment and/or adverse reactions to therapy. Since 2020, subcutaneous infliximab (IFX-SC) has been available for treating CD patients, characterized by its stable and high trough level (TL) concentration in blood. It is possible that one consequence of this property of IFX-SC is its lower rate of immunogenicity. We present a prospective study of patients diagnosed with CD with severe to refractory courses, treated with IFX-SC. The aim of the study was to monitor the immunogenicity of IFX-SC, including the dynamics of TL and anti-drug antibodies (anti-IFX). The dynamics of clinical, imaging, and laboratory markers of CD over one year of monitoring and treatment are described. Materials and methods: The study included 23 patients diagnosed with CD who had failed 2 to 6 previous lines of biological therapy, one of which was intravenous infliximab (IFX-IV). Patients were divided into two arms of induction therapy based on the presence of anti-IFX. Maintenance therapy consisted of 120 mg s.c. every 14 days, and intensification was 240 mg s.c. every 14 days if necessary. Patients were monitored at weeks W0, W4, W14, W30, and W52, recording Harvey-Bradshaw Index (HBI), serum C-reactive protein (CRP), fecal calprotectin (FC) concentrations, drug trough levels (TL IFX) and serum anti-drug antibodies (anti-IFX). Endoscopic and ultrasonographic disease scores (SES-CD and IUS) were determined, and HLA DQA1*05 haplotype was examined in all patients. Data were analyzed using MedCalc® Statistical Software with non-parametric statistical methods and binary logistic regression. Results: 52-week persistence on IFX-SC treatment was recorded in 13 out of 23 patients (56.5%), with a significant decrease in all monitored clinical, imaging, and laboratory markers of CD activity. During the therapy, 8 out of 16 initially anti-IFX positive individuals seroconverted to negative anti-IFX (50%). None of the patients treated with IFX-SC in W52 needed concomitant immunomodulator treatment. No new sensitization to infliximab was recorded in the cohort during the 52-week therapy. Conclusion: The subcutaneous route of infliximab administration may be a suitable and successful solution in situations where reinduction of infliximab therapy is desired, including patients with the presence of neutralizing antibodies against the drug.


infliximab, subcutaneous infliximab, Crohn’s disease, anti-infliximab antibodies, immunogenicity, trough infliximab levels, biologic therapy, inflammatory bowel disease

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1. Knight DM, Trinh H, Le J et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993; 30(16): 1443–1453. doi: 10.1016/ 0161-5890(93)90106- l.
2. Schnitzler F, Fidder H, Ferrante M et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut 2009; 58(4): 492–450. doi: 10.1136/gut.2008.155812.
3. Assa A, Hartman C, Weiss B et al. Long-term outcome of tumor necrosis factor alpha antagonist’s treatment in pediatric Crohn’s disease. J Crohns Colitis 2013; 7(5): 369–376. doi: 10.1016/j.crohns.2012.03.006.
4. Tighe D, McNamara D. Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease. World J Gastroenterol 2017; 23(3): 414–425: doi: 10.3748/wjg.v23.i3. 414.
5. Albshesh A, Taylor J, Savarino EV et al. Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study. J Clin Med 2021; 10(13): 2914. doi: 10.3390/jcm10132914.
6. Little RD, Ward MG, Wright E et al. Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics. J Clin Med 2022; 11(20): 6173. doi: 10.3390/jcm11206173.
7. Kucharzik T, Wilkens R, D‘Agostino MA et al. STARDUST Intestinal Ultrasound study group. Early Ultrasound Response and Progressive Transmural Remission After Treatment with Ustekinumab in Crohn’s Disease. Clin Gastroenterol Hepatol 2023; 21(1): 153–163.e12. doi: 10.1016/j.cgh.2022.05.055.
8. Daperno M, D’Haens G, Van Assche G et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc 2004; 60(4): 505–512. doi: 10.1016/s0016-5107(04)01878-4.
9. Malissen B, Tamoutounour S, Henri S. The origins and functions of dendritic cells and macrophages in the skin. Nat Rev Immunol 2014; 14(6): 417–428. doi: 10.1038/nri3683.
10. Kim H, Alten R, Cummings F et al. Innovative approaches to biologic development on the trail of CT-P13: Biosimilars, value-added medicines, and biobetters. MAbs 2021; 13(1): 1868078. doi: 10.1080/19420862.2020.1868078.
11. Bar-Yoseph H, Pressman S, Blatt A et al. Infliximab-Tumor Necrosis Factor Complexes Elicit Formation of Anti-Drug Antibodies. Gastroenterology 2019; 157(5): 1338–1351.e8. doi: 10.1053/j.gastro.2019.08.009.
12. Schreiber S, Jang BI, Borzan V et al. Novel Formulation of CT-P13 (Infliximab Biosimilar) for Subcutaneous Administration: Initial Results from a Phase I Open-Label Randomized Controlled Trial in Patients with Active Crohn’s Disease. Gastroenterology 2018; 154: 1371. doi: 10.1016/S0016-5085(18)34477-9.
13. Smith PJ, Critchley L, Storey D et al. Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab (Ct-P13): A Multi-Centre Cohort Study. J Crohn’s Colitis 2022; 16(9): 1436–1446. doi: 10.1093/ecco-jcc/jjac053.
14. Husman J, Matthes K, Gilger M et al. Subcutaneous infliximab in IBD patients with previous immunogenic failure of intravenous infliximab. J Crohns Colitis 2023; 17(Suppl): i920.
15. D‘Haens G, Reinisch W, Schreiber S et al. Comparison of combination subcutaneous infliximab and an immunomodulator versus subcutaneous infliximab monotherapy: post-hoc analysis of a randomised clinical trial (UEG Week 2021). 2021 [online]. Dostupné z: https: // tions/1284.
16. Kennedy NA, Heap GA, Green HD et al. UK Inflammatory Bowel Disease Pharmacogenetics Study Group. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: a prospective, multicentre, cohort study. Lancet Gastroenterol Hepatol 2019; 4(5): 341–353. doi: 10.1016/S2468-1253(19)30012-3.
17. Lionetti P, Bronzini F, Salvestrini C et al. Response to infliximab is related to disease duration in paediatric Crohn‘s disease. Aliment Pharmacol Ther 2003; 18(4): 425–431. doi: 10.1046/j.1365-2036.2003.01672.x.
18. Juillerat P, Sokol H, Froehlich F et al. Factors associated with durable response to infliximab in Crohn’s disease 5 years and beyond: a multicenter international cohort. Inflamm Bowel Dis 2015; 21(1): 60–70. doi: 10.1097/MIB. 0000000000000225.

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