Therapeutic Drug Monitoring of Biologics: Current Practice, Challenges and Opportunities – a Workshop Report

Lesko LJ, Schmidt S. Individualization of Drug Therapy: History, Present State, and Opportunities for the Future. Clin Pharm Therap. 2012;92(4):458–66. https://doi.org/10.1038/clpt.2012.113.

Article  CAS  PubMed  Google Scholar 

Garcês S, Antunes M, Benito-Garcia E, da Silva JC, Aarden L, Demengeot J. A preliminary algorithm introducing immunogenicity assessment in the management of patients with RA receiving tumour necrosis factor inhibitor therapies. Ann Rheum Dis. 2014;73(6):1138–43. https://doi.org/10.1136/annrheumdis-2013-203296.

Article  CAS  PubMed  Google Scholar 

Sofia MA, Rubin DT. Current approaches for optimizing the benefit of biologic therapy in ulcerative colitis. Therap Adv Gastroenterol. 2016;9(4):548–59. https://doi.org/10.1177/1756283x16643242.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartelds GM, Krieckaert CL, Nurmohamed MT, et al. Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up. JAMA. 2011;305(14):1460–8. https://doi.org/10.1001/jama.2011.406.

Article  CAS  PubMed  Google Scholar 

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(10):1580-1588.e3. https://doi.org/10.1016/j.cgh.2017.03.031.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maxfield K, Milligan L, Wang L, et al. Proceedings of a Workshop: Precision Dosing: Defining the Need and Approaches to Deliver Individualized Drug Dosing in the Real-World Setting. Clin Pharmacol Ther. 2021;109(1):25–8. https://doi.org/10.1002/cpt.1933.

Article  PubMed  Google Scholar 

Papamichael K, Gils A, Rutgeerts P, et al. Role for therapeutic drug monitoring during induction therapy with TNF antagonists in IBD: evolution in the definition and management of primary nonresponse. Inflamm Bowel Dis. 2015;21(1):182–97. https://doi.org/10.1097/mib.0000000000000202.

Article  PubMed  Google Scholar 

Miligkos M, Papamichael K, VandeCasteele N, et al. Efficacy and safety profile of anti-tumor necrosis factor-α versus anti-integrin agents for the treatment of crohn’s disease: a network meta-analysis of indirect comparisons. Clin Ther. 2016;38(6):1342-1358.e6. https://doi.org/10.1016/j.clinthera.2016.03.018.

Article  CAS  PubMed  Google Scholar 

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(5):341–53. https://doi.org/10.1016/s2468-1253(19)30012-3.

Article  PubMed  Google Scholar 

Deyhim T, Cheifetz AS, Papamichael K. Drug Clearance in patients with inflammatory bowel disease treated with biologics. J Clin Med. 2023;12(22). https://doi.org/10.3390/jcm12227132.

Mould DR, D’Haens G, Upton RN. Clinical decision support tools: the evolution of a revolution. Clin Pharmacol Ther. 2016;99(4):405–18. https://doi.org/10.1002/cpt.334.

Article  CAS  PubMed  Google Scholar 

Strik AS, Löwenberg M, Mould DR, et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand J Gastroenterol. 2021;56(2):145–54. https://doi.org/10.1080/00365521.2020.1856405.

Article  CAS  PubMed  Google Scholar 

Dubinsky MC, Mendiolaza ML, Phan BL, Moran HR, Tse SS, Mould DR. Dashboard-Driven Accelerated Infliximab Induction Dosing Increases Infliximab Durability and Reduces Immunogenicity. Inflamm Bowel Dis. 2022;28(9):1375–85. https://doi.org/10.1093/ibd/izab285.

Article  PubMed  Google Scholar 

Desai DC, Dherai AJ, Strik A, Mould DR. Personalized dosing of infliximab in patients with inflammatory bowel disease using a bayesian approach: a next step in therapeutic drug monitoring. J Clin Pharmacol. 2023;63(4):480–9. https://doi.org/10.1002/jcph.2189.

Article  CAS  PubMed  Google Scholar 

Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(6):1296-1307.e5. https://doi.org/10.1053/j.gastro.2014.08.035.

Article  CAS  PubMed  Google Scholar 

Syversen SW, Jørgensen KK, Goll GL, et al. Effect of therapeutic drug monitoring vs standard therapy during maintenance infliximab therapy on disease control in patients with immune-mediated inflammatory diseases: a randomized clinical trial. JAMA. 2021;326(23):2375–84. https://doi.org/10.1001/jama.2021.21316.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59(1):49–54. https://doi.org/10.1136/gut.2009.183095.

Article  CAS  PubMed  Google Scholar 

Paul S, Del Tedesco E, Marotte H, et al. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2013;19(12):2568–76. https://doi.org/10.1097/MIB.0b013e3182a77b41.

Article  PubMed  Google Scholar 

Maser EA, Villela R, Silverberg MS, Greenberg GR. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin Gastroenterol Hepatol. 2006;4(10):1248–54. https://doi.org/10.1016/j.cgh.2006.06.025.

Article  CAS  PubMed  Google Scholar 

VandeCasteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(7):1320-9.e3. https://doi.org/10.1053/j.gastro.2015.02.031.

Article  CAS  Google Scholar 

Mastorino L, Susca S, Cariti C, et al. “Superresponders” at biologic treatment for psoriasis: a comparative study among IL17 and IL23 inhibitors. Exp Dermatol. 2023;32(12):2187–8. https://doi.org/10.1111/exd.14731.

Article  PubMed  Google Scholar 

Jairath V, Yarur A, Osterman MT, et al. ENTERPRET: a randomized controlled trial of vedolizumab dose optimization in patients with ulcerative colitis who have early nonresponse. Clin Gastroenterol Hepatol. 2024;22(5):1077-1086.e13. https://doi.org/10.1016/j.cgh.2023.10.029.

Article  CAS  PubMed  Google Scholar 

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. https://doi.org/10.1097/mib.0000000000000156.

Article  PubMed  Google Scholar 

Assa A, Matar M, Turner D, et al. Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn’s disease compared with reactive monitoring. Gastroenterology. 2019;157(4):985-996.e2. https://doi.org/10.1053/j.gastro.2019.06.003.

Article  CAS  PubMed  Google Scholar 

Sánchez-Hernández JG, Rebollo N, Martin-Suarez A, Calvo MV, Muñoz F. A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease. Br J Clin Pharmacol. 2020;86(6):1165–75. https://doi.org/10.1111/bcp.14229.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Syed N, Tolaymat M, Brown SA, Sivasailam B, Cross RK. Proactive Drug Monitoring Is Associated With Higher Persistence to Infliximab and Adalimumab Treatment and Lower Healthcare Utilization Compared With Reactive and Clinical Monitoring. Crohns Colitis 360. 2020;2(3):otaa050. https://doi.org/10.1093/crocol/otaa050.

Lyles JL, Mulgund AA, Bauman LE, et al. Effect of a practice-wide anti-TNF proactive therapeutic drug monitoring program on outcomes in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2021;27(4):482–92. https://doi.org/10.1093/ibd/izaa102.

Article  PubMed  Google Scholar 

Gasparetto M, Burgess N, Naik S, et al. Advantages of proactive therapeutic drug monitoring in a prospective cohort of children with inflammatory bowel disease treated with anti-tumour necrosis factor. J Pediatr Gastroenterol Nutr. 2022;74(4):484–9. https://doi.org/10.1097/mpg.0000000000003389.

Article  CAS  PubMed  Google Scholar 

Kang B, Moon JS, Lee YJ, et al. DOP83 Proactive dosing is superior to clinically based dosing in terms of endoscopic healing in paediatric patients with Crohn’s disease receiving maintenance infliximab: A randomized controlled trial. J Crohn’s and Colitis. 2023;17(Supplement_1):i159-i159. https://doi.org/10.1093/ecco-jcc/jjac190.0123.

Fernandes SR, Bernardo S, Saraiva S, et al. Proactive infliximab monitoring improves the rates of transmural remission in crohn’s disease: a propensity score-matched analysis. Inflamm Bowel Dis. 2023;

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