Monitoring of infliximab treatment in inflammatory bowel diseases – basic knowledge and current data based on clinical trials in a population of Polish patients
DOI:
https://doi.org/10.15584/ejcem.2022.3.1Keywords:
infliximab, Crohn’s disease, therapeutic drug monitoring, ulcerative colitisAbstract
Introduction and aim. Infliximab is the oldest biological drug belonging to the group of tumor necrosis factor antagonists. Despite the availability of many new biological therapies, this drug still plays an important role in the treatment of inflammatory bowel diseases. However, a significant problem related to pharmacotherapy is the high inter-individual variability of the response.
Material and methods. This study presents results of the research on the treatment with infliximab in the inflammatory bowel disease (IBD) patients including our own experience in Polish IBD patients.
Analysis of the literature. Therapeutic failure while using infliximab can be attributed partly to inadequate serum concentrations of the drug and the development of anti-drug antibodies. Many studies have attempted to find a relationship between the specific level of infliximab and the achieved healing effect. These analyses show that the optimal level of the drug differs depending on the type of disease, its phenotype, and therapeutic goal and that the optimization of infliximab therapy remains an open topic. Two studies involving the population of Polish IBD patients examined the level of infliximab during and after induction, as well as the frequency of anti-drug antibodies. Two studies involving a population of Polish IBD patients examined the level of infliximab during and after induction, as well as the frequency of anti-drug antibodies. These studies demonstrated the need for monitoring infliximab treatment at weeks 6 and 14.
Conclusion. Reactive monitoring is believed to enable the most rational treatment decisions; however, experts also recommend that proactive monitoring should measure infliximab concentrations at the end of induction and at least once during maintenance treatment.
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References
Pasternak G, Aebisher D, Filip R, Bartusik-Aebisher D. Inflammatory bowel disease: clinical aspects. Eur J Clin Exp Med. 2018;16(4):341–345.
Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307–317.
Queiroz NSF, Regueiro M. Safety considerations with biologics and new inflammatory bowel disease therapies. Curr Opin Gastroenterol. 2020;36(4):257–264.
Hemperly A, Vande Casteele N. Clinical Pharmacokinetics and Pharmacodynamics of Infliximab in the Treatment of Inflammatory Bowel Disease. Clin Pharmacokinet. 2018;57(8):929–942.
Baert FJ, Rutgeerts PR. Anti-TNF strategies in Crohn’s disease: mechanisms, clinical effects, indications. Int J Colorectal Dis. 1999;14(1):47–51.
Ngo B, Farrell CP, Barr M. Tumor necrosis factor blockade for treatment of inflammatory bowel disease: efficacy and safety. Curr Mol Pharmacol. 2010;3(3):145–152.
Pękala A, Aebisher D, Pardak P, Filip R. Efficacy and safety of biosimilar IFX (CT-P13) and adalimumab in patients with active fistulizing perianal Crohn’s disease naïve to anti-TNF therapy: preliminary results from the POLIBD study. Eur J Clin Exp Med. 2019;17(1):12–15.
Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease. A review. Am J Gastroenterol. 2009;104:760–777.
Sandborn WJ. Tailoring treatment to the individual patient: drug monitoring. Dig Dis. 2014;32(Suppl 1):88–91.
Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997;337:1029–1035.
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.
Kamm MA. Review article: biological drugs in Crohn's disease. Food Pharmacy. 2006;24(Suppl 3):80–89.
Adedokun O, Sandborn W, Feagan GB, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(6):1296–1307.
Vande Casteele N, Jeyarajah J, Jairath V, Feagan BG, Sandborn WJ. Infliximab Exposure-Response Relationship and Thresholds Associated With Endoscopic Healing in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019;17:1814–1821.
Guberna L, Nyssen O, Chaparro M, Gisbert J. Frequency and Effectiveness of Empirical Anti-TNF Dose Intensification in Inflammatory Bowel Disease: Systematic Review with Meta-Analysis. J Clin Med. 2021;10(10):2132.
Gibson DJ, Heetun ZS, Redmond CE, et al. An Accelerated Infliximab Induction Regimen Reduces the Need for Early Colectomy in Patients with Acute Severe Ulcerative Colitis. Clin Gastroenterol Hepatol. 2015;13:330–335.
Nalagatla H, Falloon K, Tran G, et al. Effect of Accelerated Infliximab Induction on Short -and Long- term Outcomes of Acute Severe Ulcerative Colitis: A Retrospective Multicenter Study and Meta-analysis. Clin Gastroenterol Hepatol. 2019;17(3):502–509.
Chao C, Al Khoury A, Aruljothy A, et al. High-Dose Infliximab Rescue Therapy for Hospitalized Acute Severe Ulcerative Colitis Does Not Improve Colectomy-Free Survival. Dig Dis Sci. 2019;64(2):518–523.
Moore C, Corbett G, Moss AC. Systematic review and meta-analysis: serum infliximab levels during maintenance therapy and outcomes in inflammatory bowel disease. J Crohns Colitis. 2016;10:619–625.
Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S. American Gastroentero-logical Association Institute Clinical Guidelines Committee, American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology. 2017;153:827–834.
Papamichael K, Rakowsky S, Rivera S, Cheifetz AS, Osterman MT. Infliximab trough concentrations during maintenance therapy are associated with endoscopic and histologic healing in ulcerative colitis. Aliment Pharmacol Ther. 2018,47(4):478–484.
Yarur AJ, Kanagala V, Stein DJ, et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn’s disease. Aliment Pharmacol. Ther. 2017;45:933–940.
Papamichael K, Rakowsky S, Rivera C, Cheifetz A, Osterman M. Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease. Inflamm Bowel Dis. 2018;15;24(10):2266–2271.
Pękala A, Filip R. Levels of Biosimilar Infliximab during and after Induction Treatment in Crohn’s Disease and Ulcerative Colitis—A Prospective Polish Population Study. J Clin Med. 2021;10(22):5311.
Cornillie F, Hanauer SB, Diamond RH, et al. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: A retrospective analysis of the ACCENT I trial. Gut. 2014;63:1721–1727.
Kennedy NA, Heap GA, Green HD, et al. 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;4:341–353.
Casteele NV, Jeyarajah J, Jairath V, Feagan BG, Sandborn WJ. Infliximab Exposure Response Relationship and Thresholds Associated with Endoscopic Healing in Patients with Ulcerative Colitis. Clin Gastroenterol Hepatol. 2019;17:1814–1821.
Papamichael K, Cheifetz A. Letter: Infliximab concentrations during induction therapy - one size doesn’t fit all. Aliment Pharmacol Ther. 2018;47(9):1334–1335.
Gonczi L, Vegh Z, Golovics PA. Prediction of short- and medium-term efficacy of biosimilar infliximab therapy. Do trough levels and antidrug antibody levels or clinical and biochemical markers play the more important role? J Crohns Colitis. 2017;11:697–705.
Darrouzain F, Bian S, Desvignes C. Methods for measuring serum concentrations of monoclonal antibodies and anti-biopharmaceutical antibodies in patients; how to measure accurately and clinically relevant levels. Ther Drug Monit. 2017;39(4):316–321.
Dreesen E, Bossuyt P, Mulleman D, Gils A, Pascual-Salcedo D. Practical recommendations for the use of therapeutic drug monitoring of biopharmaceuticals in inflammatory diseases. Clin Pharmacol. 2017;3(9):101–111.
Atiqi S, Hooijberg F, Loeff F, Rispens T, Wolbink GJ. Immunogenicity of TNF-Inhibitors. Front Immunol. 2020;11:312.
Nechansky A. HAHA–nothing to laugh about. Measuring the immunogenicity (human anti-human antibody response) induced by humanized monoclonal antibodies applying ELISA and SPR technology. J Pharm Biomed Anal. 2010;51:252–254.
Pękala A, Filip R, Aebisher D. Anti-Drug Antibodies in Patients with Inflammatory Bowel Diseases Treated with Biosimilar Infliximab: A Prospective Cohort Study. J Clin Med. 2021;10:2653.
Casteele VN, Khanna R, Levesque BG, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. Gut. 2015;6:1539–1545.
Imbrechts M, Van Stappen T, Compernolle G, Tops S, Gils A. Anti-infliximab antibodies: How to compare old and new data? J Pharm Biomed Anal. 2022;177:112842.
Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2019;17(9):1655–1668.
Vande Casteele N, Gils A, Singh S, et al. Antibody response to infliximab and its impact on pharmacokinetics can be transient. Am J Gastroenterol. 2013;108:962–971.
Bloem K, Hernandez-Breijo B, Martinez-Feito A, Rispens T. Immunogenicity of therapeutic antibodies: monitoring antidrug antibodies in a clinical context. Ther Drug Monit. 2017;39:327–332.
Van Schie KA, Kruithof S, Ooijevaar-de Heer P, et al. Restricted immune activation and internalisation of anti-idiotype complexes between drug and antidrug antibodies. Ann Rheum Dis. 2018;77:1471–1479.
Thomas SS, Borazan N, Barroso N, et al. Comparative immunogenicity of TNF inhibitors: impact on clinical efficacy and tolerability in the management of autoimmune diseases. a systematic review and meta-analysis. Bio Drugs. 2015;29:241–258.
Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49:633–659.
Drobne D, Bossuyt P, Breynaert C, et al, Withdrawal of immunomodulators after co-treatment does not reduce trough level of infliximab in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2015;13(3):514–521.
Van Stappen T, Vande Casteele N, Van Assche G, Ferrante M, Vermeire S, Gils A. Clinical relevance of detecting anti-infliximab antibodies with a drug-tolerant assay: post hoc analysis of the TAXIT trial. Gut. 2018;67(5):818–826.
Ben-Horin S, Waterman M, Kopylov U, et al. Addition of an immunomodulator to infliximab therapy eliminates antidrug antibodies in serum and restores clinical response of patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(4):444–447.
Ward MG, Irving PM, Sparrow MP. How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease? World J Gastroenterol. 2015;21(40):11331–11342.
Vermeire S, Noman M, Van Assche G, Baert F, D’Haens G, Rutgeerts P. Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut. 2007;56:1226–1231.
Sandborn WJ. Tailoring treatment to the individual patient: drug monitoring. Dig Dis. 2014;32(Suppl 1):88–91.
Guidi L, Pugliese D, Panici Tonucci T, et al. Therapeutic drug monitoring is more cost-effective than a clinically-based approach in the management of loss of response to infliximab in inflammatory bowel disease: an observational multi-centre study. J Crohns Colitis. 2018;12(9):1079–1088.
Guberna L, Nyssen OP, Chaparro M, Gisbert JP. Frequency and Effectiveness of Empirical Anti-TNF Dose Intensification in Inflammatory Bowel Disease: Systematic Review with Meta-Analysis. J Clin Med. 2021;10(10);2132.
Bartelds GM, Wijbrandts CA, Nurmohamed MT, et al. Anti-infliximab and anti-adalimumab antibodies in relation to response to adalimumab in infliximab switchers and anti-tumour necrosis factor naive patients: a cohort study. Ann Rheum Dis. 2010;69:817–821.
Qiu Y, Chen BL, Mao R, et al. Systematic review with meta-analysis: Loss of response and requirement of anti-TNF alpha dose intensification in Crohn's disease. J Gastroenterol. 2017;(52):535–554.
D’Haens GR, Vermeire S, Lambrecht G, et al. 692 drug-level based dosing versus symptom-based dose adaptation in patients with Crohn’s disease: a prospective, randomized multicenter study (TAILORIX). Gastroenterology. 2016;150(4):143.
Vande Casteele NV, Ferrante M, Van Assche G, et al. Trough Concentrations of Infliximab Guide Dosing for Patients with Inflammatory Bowel Disease. Gastroenterology. 2015;148:1320–1329.e3.
D'Haens D, Vermeire S, Lambrecht G, et al. Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, and Corticosteroid-Free Remission in Patients With Active Luminal Crohn's Disease. Gastroenterology. 2018;154(5):1343-1351.e1.
Van Hoeve K, Dreesen E, Hoffman I, et al. Higher infliximab trough levels are associated with better outcome in paediatric patients with inflammatory bowel disease. J Crohns Colitis. 2018;12:1316–1325.
Vande Casteele N, Jeyarajah J, Jairath V, Feagan BG, Sandborn W. Infliximab exposure-response relationship and thresholds associated with endoscopic healing in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17(9):1814-1821.e1
Vaughn BP, Martinez-Vazquez M. Patwardhan VR, Moss AC, Sandborn WJ, Cheifetz AS, Proactive therapeutic concentration monitoring of infliximab may improve outcomes for patients with inflammatory bowel disease: results from a pilot observational study. Inflamm Bowel Dis. 2014;20(11):1996‒2003.
Papamichael K, Chachu KA, Vajravelu RK, et al. Improved long-term outcomes of patients with inflammatory bowel disease receiving proactive compared with reactive monitoring of serum concentrations of infliximab. Clin Gastroenterol Hepatol. 2017;15:1580–1588.
Colombel JF, Adedokun OJ, Gasink C, et al. Combination therapy with infliximab and azathioprine improves infliximab pharmacokinetic features and efficacy-a post-hoc analysis. Clin Gastroenterol Hepatol. 2018;17(8):1525-1532.e1.
Dreesen E, Baert F, Laharie D, et al. Monitoring a Combination of Calprotectin and Infliximab Identifies Patients With Mucosal Healing of Crohn’s Disease. Clin Gastroenterol Hepatol. 2020;18:637–646.
Vande Casteele N, Jeyarajah J, Jairath V, Feagan BG, Sandborn WJ. Infliximab exposure-response relationship and thresholds associated with endoscopic healing in patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:1814–1821.
Sparrow MP, Papamichael K, Ward MG, et al. Therapeutic Drug Monitoring of Biologics During Induction to Prevent Primary Non-Response, J Crohns Colitis. 2020;14(4):542–556.
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