Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Factors to Consider with Therapeutic Drug Monitoring
3.1.1. Proactive vs. Reactive Therapeutic Drug Monitoring
3.1.2. Timing of Therapeutic Drug Monitoring
3.1.3. Methods of Measuring Drug Levels and Anti-Drug Antibodies (ADAs)
4. Advanced Therapies Using Therapeutic Drug Monitoring
4.1. Monoclonal Antibodies
4.1.1. Ustekinumab
Pharmacokinetics and Pharmacodynamics
Therapeutic Drug Monitoring
4.1.2. Vedolizumab
Pharmacokinetics and Pharmacodynamics
Therapeutic Drug Monitoring
4.1.3. Risankizumab
Pharmacokinetics and Pharmacodynamics
Therapeutic Drug Monitoring
4.2. Small-Molecule Therapy
4.2.1. Janus Kinase (JAK) Inhibitors
Pharmacokinetics and Pharmacodynamics
Therapeutic Drug Monitoring
4.2.2. Ozanimod
Pharmacokinetics and Pharmacodynamics
Therapeutic Drug Monitoring
5. Discussion
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
- Turner, D.; Ricciuto, A.; Lewis, A.; D’Amico, F.; Dhaliwal, J.; Griffiths, A.M.; Bettenworth, D.; Sandborn, W.J.; Sands, B.E.; Reinisch, W.; et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology 2021, 160, 1570–1583. [Google Scholar] [CrossRef]
- Vande Casteele, N.; Ferrante, M.; Van Assche, G.; Ballet, V.; Compernolle, G.; Van Steen, K.; Simoens, S.; Rutgeerts, P.; Gils, A.; Vermeire, S. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology 2015, 148, 1320–1329.e3. [Google Scholar] [CrossRef]
- Albader, F.; Golovics, P.A.; Gonczi, L.; Bessissow, T.; Afif, W.; Lakatos, P.L. Therapeutic drug monitoring in inflammatory bowel disease: The dawn of reactive monitoring. World J. Gastroenterol. 2021, 27, 6231–6247. [Google Scholar] [CrossRef]
- Roblin, X.; Rinaudo, M.; Del Tedesco, E.; Phelip, J.M.; Genin, C.; Peyrin-Biroulet, L.; Paul, S. Development of an algorithm incorporating pharmacokinetics of adalimumab in inflammatory bowel diseases. Am. J. Gastroenterol. 2014, 109, 1250–1256. [Google Scholar] [CrossRef]
- Negoescu, D.M.; Enns, E.A.; Swanhorst, B.; Baumgartner, B.; Campbell, J.P.; Osterman, M.T.; Papamichael, K.; Cheifetz, A.S.; Vaughn, B.P. Proactive vs. Reactive Therapeutic Drug Monitoring of Infliximab in Crohn’s Disease: A Cost-Effectiveness Analysis in a Simulated Cohort. Inflamm. Bowel Dis. 2020, 26, 103–111. [Google Scholar] [CrossRef]
- Shah, R.; Hoffman, G.R.; El-Dallal, M.; Goldowsky, A.M.; Chen, Y.; Feuerstein, J.D. Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults with Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis. J. Crohn’s Colitis 2020, 14, 1057–1065. [Google Scholar] [CrossRef]
- Davidov, Y.; Ungar, B.; Bar-Yoseph, H.; Carter, D.; Haj-Natour, O.; Yavzori, M.; Chowers, Y.; Eliakim, R.; Ben-Horin, S.; Kopylov, U. Association of Induction Infliximab Levels with Clinical Response in Perianal Crohn’s Disease. J. Crohn’s Colitis 2017, 11, 549–555. [Google Scholar] [CrossRef]
- Papamichael, K.; Rakowsky, S.; Rivera, C.; Cheifetz, A.S.; Osterman, M.T. Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn’s Disease. Inflamm. Bowel Dis. 2018, 24, 2266–2271. [Google Scholar] [CrossRef]
- Steenholdt, C.; Brynskov, J.; Thomsen, O.; Munck, L.K.; Fallingborg, J.; Christensen, L.A.; Pedersen, G.; Kjeldsen, J.; Jacobsen, B.A.; Oxholm, A.S.; et al. Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: A randomised, controlled trial. Gut 2014, 63, 919–927. [Google Scholar] [CrossRef]
- Paul, S.; Del Tedesco, E.; Marotte, H.; Rinaudo-Gaujous, M.; Moreau, A.; Phelip, J.M.; Genin, C.; Peyrin-Biroulet, L.; Roblin, X. Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease: A prospective study. Inflamm. Bowel Dis. 2013, 19, 2568–2576. [Google Scholar] [CrossRef]
- Fernandes, S.R.; Bernardo, S.; Simões, C.; Gonçalves, A.R.; Valente, A.; Baldaia, C.; Moura Santos, P.; Correia, L.A.; Tato Marinho, R. Proactive Infliximab Drug Monitoring Is Superior to Conventional Management in Inflammatory Bowel Disease. Inflamm. Bowel Dis. 2020, 26, 263–270. [Google Scholar] [CrossRef] [PubMed]
- Seow, C.H.; Newman, A.; Irwin, S.P.; Steinhart, A.H.; Silverberg, M.S.; Greenberg, G.R. Trough serum infliximab: A predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut 2010, 59, 49–54. [Google Scholar] [CrossRef]
- Maser, E.A.; Villela, R.; Silverberg, M.S.; Greenberg, G.R. Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease. Clin. Gastroenterol. Hepatol. 2006, 4, 1248–1254. [Google Scholar] [CrossRef] [PubMed]
- Karmiris, K.; Paintaud, G.; Noman, M.; Magdelaine-Beuzelin, C.; Ferrante, M.; Degenne, D.; Claes, K.; Coopman, T.; Van Schuerbeek, N.; Van Assche, G.; et al. Influence of trough serum levels and immunogenicity on long-term outcome of adalimumab therapy in Crohn’s disease. Gastroenterology 2009, 137, 1628–1640. [Google Scholar] [CrossRef] [PubMed]
- Battat, R.; Kopylov, U.; Bessissow, T.; Bitton, A.; Cohen, A.; Jain, A.; Martel, M.; Seidman, E.; Afif, W. Association Between Ustekinumab Trough Concentrations and Clinical, Biomarker, and Endoscopic Outcomes in Patients with Crohn’s Disease. Clin. Gastroenterol. Hepatol. 2017, 15, 1427–1434.e2. [Google Scholar] [CrossRef]
- Singh, S.; Dulai, P.S.; Vande Casteele, N.; Battat, R.; Fumery, M.; Boland, B.S.; Sandborn, W.J. Systematic review with meta-analysis: Association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases. Aliment. Pharmacol. Ther. 2019, 50, 848–857. [Google Scholar] [CrossRef] [PubMed]
- Pouillon, L.; Vermeire, S.; Bossuyt, P. Vedolizumab trough level monitoring in inflammatory bowel disease: A state-of-the-art overview. BMC Med. 2019, 17, 89. [Google Scholar] [CrossRef] [PubMed]
- Sparrow, M.P.; Papamichael, K.; Ward, M.G.; Riviere, P.; Laharie, D.; Paul, S.; Roblin, X. Therapeutic Drug Monitoring of Biologics During Induction to Prevent Primary Non-Response. J. Crohn’s Colitis 2020, 14, 542–556. [Google Scholar] [CrossRef]
- Papamichael, K.; Van Stappen, T.; Vande Casteele, N.; Gils, A.; Billiet, T.; Tops, S.; Claes, K.; Van Assche, G.; Rutgeerts, P.; Vermeire, S.; et al. Infliximab Concentration Thresholds During Induction Therapy Are Associated with Short-term Mucosal Healing in Patients with Ulcerative Colitis. Clin. Gastroenterol. Hepatol. 2016, 14, 543–549. [Google Scholar] [CrossRef]
- Chiu, Y.L.; Rubin, D.T.; Vermeire, S.; Louis, E.; Robinson, A.M.; Lomax, K.G.; Pollack, P.F.; Paulson, S.K. Serum adalimumab concentration and clinical remission in patients with Crohn’s disease. Inflamm. Bowel Dis. 2013, 19, 1112–1122. [Google Scholar] [CrossRef]
- Dreesen, E.; Faelens, R.; Van Assche, G.; Ferrante, M.; Vermeire, S.; Gils, A.; Bouillon, T. Optimising infliximab induction dosing for patients with ulcerative colitis. Br. J. Clin. Pharmacol. 2019, 85, 782–795. [Google Scholar] [CrossRef]
- Dreesen, E.; Verstockt, B.; Bian, S.; de Bruyn, M.; Compernolle, G.; Tops, S.; Noman, M.; Van Assche, G.; Ferrante, M.; Gils, A.; et al. Evidence to Support Monitoring of Vedolizumab Trough Concentrations in Patients with Inflammatory Bowel Diseases. Clin. Gastroenterol. Hepatol. 2018, 16, 1937–1946.e8. [Google Scholar] [CrossRef]
- Williet, N.; Boschetti, G.; Fovet, M.; Di Bernado, T.; Claudez, P.; Del Tedesco, E.; Jarlot, C.; Rinaldi, L.; Berger, A.; Phelip, J.M.; et al. Association between Low Trough Levels of Vedolizumab during Induction Therapy for Inflammatory Bowel Diseases and Need for Additional Doses within 6 Months. Clin. Gastroenterol. Hepatol. 2017, 15, 1750–1757.e3. [Google Scholar] [CrossRef]
- D’Haens, G.; Vermeire, S.; Lambrecht, G.; Baert, F.; Bossuyt, P.; Pariente, B.; Buisson, A.; Bouhnik, Y.; Filippi, J.; Vander Woude, J.; 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, 1343–1351.e1. [Google Scholar] [CrossRef] [PubMed]
- Assa, A.; Matar, M.; Turner, D.; Broide, E.; Weiss, B.; Ledder, O.; Guz-Mark, A.; Rinawi, F.; Cohen, S.; Topf-Olivestone, C.; 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, 985–996.e2. [Google Scholar] [CrossRef]
- Strik, A.S.; Löwenberg, M.; Mould, D.R.; Berends, S.E.; Ponsioen, C.I.; van den Brande, J.M.H.; Jansen, J.M.; Hoekman, D.R.; Brandse, J.F.; Duijvestein, M.; et al. Efficacy of dashboard driven dosing of infliximab in inflammatory bowel disease patients; a randomized controlled trial. Scand. J. Gastroenterol. 2021, 56, 145–154. [Google Scholar] [CrossRef] [PubMed]
- Adedokun, O.J.; Xu, Z.; Gasink, C.; Kowalski, K.; Sandborn, W.J.; Feagan, B. Population Pharmacokinetics and Exposure–Response Analyses of Ustekinumab in Patients with Moderately to Severely Active Crohn’s Disease. Clin. Ther. 2022, 44, 1336–1355. [Google Scholar] [CrossRef] [PubMed]
- Gils, A.; Vande Casteele, N.; Poppe, R.; Van de Wouwer, M.; Compernolle, G.; Peeters, M.; Brouwers, E.; Vermeire, S.; Geukens, N.; Declerck, P.J. Development of a universal anti-adalimumab antibody standard for interlaboratory harmonization. Ther. Drug. Monit. 2014, 36, 669–673. [Google Scholar] [CrossRef]
- Bendtzen, K.; Ainsworth, M.; Steenholdt, C.; Thomsen, O.; Brynskov, J. Individual medicine in inflammatory bowel disease: Monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies. Scand. J. Gastroenterol. 2009, 44, 774–781. [Google Scholar] [CrossRef] [PubMed]
- Vermeire, S.; Dreesen, E.; Papamichael, K.; Dubinsky, M.C. How, When, and for Whom Should We Perform Therapeutic Drug Monitoring? Clin. Gastroenterol. Hepatol. 2020, 18, 1291–1299. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.J.; Zhao, Y.H.; Fan, C.; Wang, Y.J.; Wang, X.Q.; Qiu, X.J.; Shen, R.L. Development of an UPLC-MS/MS Method for the Quantitative Analysis of Upadacitinib in Beagle Dog Plasma and Pharmacokinetics Study. Drug. Des. Dev. Ther. 2021, 15, 4167–4175. [Google Scholar] [CrossRef] [PubMed]
- Vande Casteele, N.; Yang, L.; Dobler, I.; Agboton, C.; McRorie Osborn, T.; Suri, A.; Lindner, D.; Smithson, G.M. Measuring Serum Vedolizumab and Vedolizumab Antibodies: Comparison of Commercial Assays with the Vedolizumab Clinical Development Assay. Ther. Drug. Monit. 2023, 45, 236–244. [Google Scholar] [CrossRef]
- 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, 9, 101–111. [Google Scholar] [CrossRef]
- Vande Casteele, N. Assays for measurement of TNF antagonists in practice. Front. Gastroenterol. 2017, 8, 236–242. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.L.; Ohrmund, L.; Hauenstein, S.; Salbato, J.; Reddy, R.; Monk, P.; Lockton, S.; Ling, N.; Singh, S. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum. J. Immunol. Methods 2012, 382, 177–188. [Google Scholar] [CrossRef] [PubMed]
- Papamichael, K.; Cheifetz, A.S. Use of anti-TNF drug levels to optimise patient management. Front. Gastroenterol. 2016, 7, 289–300. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Gasink, C.; Gao, L.-L.; Blank, M.A.; Johanns, J.; Guzzo, C.; Sands, B.E.; Hanauer, S.B.; Targan, S.; Rutgeerts, P.; et al. Ustekinumab Induction and Maintenance Therapy in Refractory Crohn’s Disease. N. Engl. J. Med. 2012, 367, 1519–1528. [Google Scholar] [CrossRef]
- Sands, B.E.; Sandborn, W.J.; Panaccione, R.; O’Brien, C.D.; Zhang, H.; Johanns, J.; Adedokun, O.J.; Li, K.; Peyrin-Biroulet, L.; Van Assche, G.; et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 2019, 381, 1201–1214. [Google Scholar] [CrossRef]
- Koutruba, N.; Emer, J.; Lebwohl, M. Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis. Ther. Clin. Risk Manag. 2010, 6, 123–141. [Google Scholar]
- Adedokun, O.J.; Xu, Z.; Marano, C.; O’Brien, C.; Szapary, P.; Zhang, H.; Johanns, J.; Leong, R.W.; Hisamatsu, T.; Van Assche, G.; et al. Ustekinumab Pharmacokinetics and Exposure Response in a Phase 3 Randomized Trial of Patients with Ulcerative Colitis. Clin. Gastroenterol. Hepatol. 2020, 18, 2244–2255.e9. [Google Scholar] [CrossRef]
- Toedter, G.P.; Blank, M.; Lang, Y.; Chen, D.; Sandborn, W.J.; de Villiers, W.J.S. Relationship of C-Reactive Protein with Clinical Response After Therapy with Ustekinumab in Crohn’s Disease. Off. J. Am. Coll. Gastroenterol. ACG 2009, 104, 2768–2773. [Google Scholar] [CrossRef]
- Vasudevan, A.; Tharayil, V.; Raffals, L.H.; Bruining, D.H.; Becker, M.; Murad, M.H.; Loftus, E.V., Jr. Systematic Review and Meta-analysis: The Association Between Serum Ustekinumab Trough Concentrations and Treatment Response in Inflammatory Bowel Disease. Inflamm. Bowel Dis. 2023, 2023, izad065. [Google Scholar] [CrossRef]
- Roblin, X.; Duru, G.; Papamichael, K.; Cheifetz, A.S.; Kwiatek, S.; Berger, A.E.; Barrau, M.; Waeckel, L.; Nancey, S.; Paul, S. Development of Antibodies to Ustekinumab Is Associated with Loss of Response in Patients with Inflammatory Bowel Disease. J. Clin. Med. 2023, 12, 3395. [Google Scholar] [CrossRef]
- Walshe, M.; Borowski, K.; Battat, R.; Hudesman, D.; Wolf, D.C.; Okada, L.; Jain, A.; Silverberg, M.S. Serum Ustekinumab Concentrations Are Associated with Remission in Crohn’s Disease Defined by a Serum-Based Endoscopic Healing Index. Crohn’s Colitis 2021, 3, otab032. [Google Scholar] [CrossRef]
- Gómez Espín, R.; Nicolás De Prado, I.; Gil Candel, M.; González Carrión, M.; Rentero Redondo, L.; Iniesta Navalón, C. Association between ustekinumab trough concentrations and biochemical outcomes in patients with Crohn’s disease. A real life study. Rev. Esp. Enferm. Dig. 2021, 113, 110–115. [Google Scholar]
- Liefferinckx, C.; Hubert, A.; Thomas, D.; Bottieau, J.; Minsart, C.; Cremer, A.; Amininejad, L.; Vallée, F.; Toubeau, J.F.; Franchimont, D. Predictive models assessing the response to ustekinumab highlight the value of therapeutic drug monitoring in Crohn’s disease. Dig. Liver Dis. 2023, 55, 366–372. [Google Scholar] [CrossRef]
- Straatmijer, T.; Biemans, V.B.C.; Moes, D.; Hoentjen, F.; Ter Heine, R.; Maljaars, P.W.J.; Theeuwen, R.; Pierik, M.; Duijvestein, M.; van der Meulen-de Jong, A.E. Ustekinumab Trough Concentrations Are Associated with Biochemical Outcomes in Patients with Crohn’s Disease. Dig. Dis. Sci. 2023, 68, 2647–2657. [Google Scholar] [CrossRef]
- Kwon, Y.; Kang, B.; Kim, E.S.; Choe, Y.H.; Kim, M.J. Comparison of Ustekinumab Trough Concentrations Measured by 2 ELISA Kits and Evaluation of Clinical Response in Crohn’s Disease. Ther. Drug. Monit. 2022, 44, 535–542. [Google Scholar] [CrossRef]
- Verdon, C.; Vande Casteele, N.; Heron, V.; Germain, P.; Afif, W. Comparison of Serum Concentrations of Ustekinumab Obtained by Three Commercial Assays in Patients with Crohn’s Disease. J. Can. Assoc. Gastroenterol. 2021, 4, 73–77. [Google Scholar] [CrossRef] [PubMed]
- Painchart, C.; Brabant, S.; Duveau, N.; Nachury, M.; Desreumaux, P.; Branche, J.; Gérard, R.; Prevost, C.L.D.; Wils, P.; Lambin, T.; et al. Ustekinumab Serum Trough Levels May Identify Suboptimal Responders to Ustekinumab in Crohn’s Disease. Dig. Dis. Sci. 2020, 65, 1445–1452. [Google Scholar] [CrossRef] [PubMed]
- Proietti, E.; Pauwels, R.W.M.; van der Woude, C.J.; Doukas, M.; Oudijk, L.; Peppelenbosch, M.P.; Grohmann, U.; Crombag, M.B.S.; de Vries, A.C.; Fuhler, G.M. Ustekinumab Tissue and Serum Levels in Patients with Crohn’s Disease Are Closely Correlated Though Not Consistently Associated with Objective Response After Induction. Inflamm. Bowel Dis. 2023, 29, 1038–1046. [Google Scholar] [CrossRef]
- Hanzel, J.; Kozelj, M.; Spes Hlastec, A.; Kurent, T.; Sever, N.; Zdovc, J.; Smrekar, N.; Novak, G.; Stabuc, B.; Grabnar, I.; et al. Ustekinumab concentrations shortly after escalation to monthly dosing may identify endoscopic remission in refractory Crohn’s disease. Eur. J. Gastroenterol. Hepatol. 2021, 33 (Suppl. S1), e831–e836. [Google Scholar] [CrossRef]
- Wyant, T.; Fedyk, E.; Abhyankar, B. An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab. J. Crohn’s Colitis 2016, 10, 1437–1444. [Google Scholar] [CrossRef]
- Zeissig, S.; Rosati, E.; Dowds, C.M.; Aden, K.; Bethge, J.; Schulte, B.; Pan, W.H.; Mishra, N.; Zuhayra, M.; Marx, M.; et al. Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease. Gut 2019, 68, 25–39. [Google Scholar] [CrossRef]
- Keizer, R.J.; Huitema, A.D.; Schellens, J.H.; Beijnen, J.H. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin. Pharmacokinet. 2010, 49, 493–507. [Google Scholar] [CrossRef]
- Rosario, M.; Dirks, N.L.; Gastonguay, M.R.; Fasanmade, A.A.; Wyant, T.; Parikh, A.; Sandborn, W.J.; Feagan, B.G.; Reinisch, W.; Fox, I. Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn’s disease. Aliment. Pharmacol. Ther. 2015, 42, 188–202. [Google Scholar] [CrossRef]
- Ward, M.G.; Sparrow, M.P.; Roblin, X. Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease: Current data and future directions. Ther. Adv. Gastroenterol. 2018, 11, 1756284818772786. [Google Scholar] [CrossRef]
- Feagan, B.G.; Rutgeerts, P.; Sands, B.E.; Hanauer, S.; Colombel, J.F.; Sandborn, W.J.; Van Assche, G.; Axler, J.; Kim, H.J.; Danese, S.; et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 2013, 369, 699–710. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Feagan, B.G.; Rutgeerts, P.; Hanauer, S.; Colombel, J.F.; Sands, B.E.; Lukas, M.; Fedorak, R.N.; Lee, S.; Bressler, B.; et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N. Engl. J. Med. 2013, 369, 711–721. [Google Scholar] [CrossRef]
- Ungar, B.; Kopylov, U.; Yavzori, M.; Fudim, E.; Picard, O.; Lahat, A.; Coscas, D.; Waterman, M.; Haj-Natour, O.; Orbach-Zingboim, N.; et al. Association of Vedolizumab Level, Anti-Drug Antibodies, and α4β7 Occupancy with Response in Patients with Inflammatory Bowel Diseases. Clin. Gastroenterol. Hepatol. 2018, 16, 697–705.e7. [Google Scholar] [CrossRef]
- Yzet, C.; Diouf, M.; Singh, S.; Brazier, F.; Turpin, J.; Nguyen-Khac, E.; Meynier, J.; Fumery, M. No Benefit of Concomitant Immunomodulator Therapy on Efficacy of Biologics That Are Not Tumor Necrosis Factor Antagonists in Patients with Inflammatory Bowel Diseases: A Meta-analysis. Clin. Gastroenterol. Hepatol. 2021, 19, 668–679.e8. [Google Scholar] [CrossRef] [PubMed]
- Hanzel, J.; Zdovc, J.; Kurent, T.; Sever, N.; Javornik, K.; Tuta, K.; Kozelj, M.; Smrekar, N.; Novak, G.; Stabuc, B.; et al. Peak Concentrations of Ustekinumab After Intravenous Induction Therapy Identify Patients with Crohn’s Disease Likely to Achieve Endoscopic and Biochemical Remission. Clin. Gastroenterol. Hepatol. 2021, 19, 111–118.e10. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Baert, F.; Danese, S.; Krznarić, Ž.; Kobayashi, T.; Yao, X.; Chen, J.; Rosario, M.; Bhatia, S.; Kisfalvi, K.; et al. Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients with Ulcerative Colitis. Gastroenterology 2020, 158, 562–572.e12. [Google Scholar] [CrossRef]
- Nassar, I.O.; Cheesbrough, J.; Quraishi, M.N.; Sharma, N. Proposed pathway for therapeutic drug monitoring and dose escalation of vedolizumab. Front. Gastroenterol. 2022, 13, 430–435. [Google Scholar] [CrossRef]
- Sivridaş, M.; Creemers, R.H.; Wong, D.R.; Boekema, P.J.; Römkens, T.E.H.; Gilissen, L.P.L.; van Bodegraven, A.A.; Loeff, F.C.; Rispens, T.; Derijks, L.J.J. Therapeutic Drug Monitoring of Vedolizumab in Inflammatory Bowel Disease Patients during Maintenance Treatment-TUMMY Study. Pharmaceutics 2023, 15, 972. [Google Scholar] [CrossRef] [PubMed]
- Guidi, L.; Pugliese, D.; Panici Tonucci, T.; Bertani, L.; Costa, F.; Privitera, G.; Tolusso, B.; Di Mario, C.; Albano, E.; Tapete, G.; et al. Early vedolizumab trough levels predict treatment persistence over the first year in inflammatory bowel disease. United Eur. Gastroenterol. J. 2019, 7, 1189–1197. [Google Scholar] [CrossRef] [PubMed]
- Al-Bawardy, B.; Ramos, G.P.; Willrich, M.A.V.; Jenkins, S.M.; Park, S.H.; Aniwan, S.; Schoenoff, S.A.; Bruining, D.H.; Papadakis, K.A.; Raffals, L.; et al. Vedolizumab Drug Level Correlation with Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease. Inflamm. Bowel Dis. 2019, 25, 580–586. [Google Scholar] [CrossRef]
- D’Haens, G.; Panaccione, R.; Baert, F.; Bossuyt, P.; Colombel, J.F.; Danese, S.; Dubinsky, M.; Feagan, B.G.; Hisamatsu, T.; Lim, A.; et al. Risankizumab as induction therapy for Crohn’s disease: Results from the phase 3 Advance and Motivate induction trials. Lancet 2022, 399, 2015–2030. [Google Scholar] [CrossRef]
- Ferrante, M.; Panaccione, R.; Baert, F.; Bossuyt, P.; Colombel, J.F.; Danese, S.; Dubinsky, M.; Feagan, B.G.; Hisamatsu, T.; Lim, A.; et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: Results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet 2022, 399, 2031–2046. [Google Scholar] [CrossRef] [PubMed]
- Pang, Y.; Khatri, A.; Suleiman, A.A.; Othman, A.A. Clinical Pharmacokinetics and Pharmacodynamics of Risankizumab in Psoriasis Patients. Clin. Pharmacokinet. 2020, 59, 311–326. [Google Scholar] [CrossRef]
- Suleiman, A.A.; Goebel, A.; Bhatnagar, S.; D’Cunha, R.; Liu, W.; Pang, Y. Population Pharmacokinetic and Exposure-Response Analyses for Efficacy and Safety of Risankizumab in Patients with Active Crohn’s Disease. Clin. Pharmacol. Ther. 2023, 113, 839–850. [Google Scholar] [CrossRef]
- Suleiman, A.A.; Minocha, M.; Khatri, A.; Pang, Y.; Othman, A.A. Population Pharmacokinetics of Risankizumab in Healthy Volunteers and Subjects with Moderate to Severe Plaque Psoriasis: Integrated Analyses of Phase I-III Clinical Trials. Clin. Pharmacokinet. 2019, 58, 1309–1321. [Google Scholar] [CrossRef] [PubMed]
- Rani Soenen, J.L. Therapeutic Drug Monitoring of Risankizumab in Psoriasis Patients (BIOLOPTIM-RIS)−Phase 4 Clinical Trial—Currently Recruiting. Available online: https://trials.psoriasis.org/trials/NCT05685940 (accessed on 21 November 2023).
- Loftus, E. A Study of the Efficacy and Safety of Risankizumab in Participants with Crohn’s Disease—Phase 3 Trial−Ongoing Trial, Recruitment Closed. Available online: https://www.mayo.edu/research/clinical-trials/cls-20358836 (accessed on 21 November 2023).
- Loftus, E.V.; Panés, J.; Lacerda, A.P.; Peyrin-Biroulet, L.; D’Haens, G.; Panaccione, R.; Reinisch, W.; Louis, E.; Chen, M.; Nakase, H.; et al. Upadacitinib Induction and Maintenance Therapy for Crohn’s Disease. N. Engl. J. Med. 2023, 388, 1966–1980. [Google Scholar] [CrossRef]
- Danese, S.; Vermeire, S.; Zhou, W.; Pangan, A.L.; Siffledeen, J.; Greenbloom, S.; Hébuterne, X.; D’Haens, G.; Nakase, H.; Panés, J.; et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: Results from three phase 3, multicentre, double-blind, randomised trials. Lancet 2022, 399, 2113–2128. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Su, C.; Sands, B.E.; D’Haens, G.R.; Vermeire, S.; Schreiber, S.; Danese, S.; Feagan, B.G.; Reinisch, W.; Niezychowski, W.; et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 2017, 376, 1723–1736. [Google Scholar] [CrossRef]
- Feagan, B.G.; Danese, S.; Loftus, E.V., Jr.; Vermeire, S.; Schreiber, S.; Ritter, T.; Fogel, R.; Mehta, R.; Nijhawan, S.; Kempiński, R.; et al. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): A phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet 2021, 397, 2372–2384. [Google Scholar] [CrossRef] [PubMed]
- Seif, F.; Khoshmirsafa, M.; Aazami, H.; Mohsenzadegan, M.; Sedighi, G.; Bahar, M. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun. Signal. 2017, 15, 23. [Google Scholar] [CrossRef]
- Darnell, J.E., Jr. STATs and gene regulation. Science 1997, 277, 1630–1635. [Google Scholar] [CrossRef]
- Pippis, E.J.; Yacyshyn, B.R. Clinical and Mechanistic Characteristics of Current JAK Inhibitors in IBD. Inflamm. Bowel Dis. 2020, 27, 1674–1683. [Google Scholar] [CrossRef] [PubMed]
- Dowty, M.E.; Lin, J.; Ryder, T.F.; Wang, W.; Walker, G.S.; Vaz, A.; Chan, G.L.; Krishnaswami, S.; Prakash, C. The Pharmacokinetics, Metabolism, and Clearance Mechanisms of Tofacitinib, a Janus Kinase Inhibitor, in Humans. Drug Metab. Dispos. 2014, 42, 759–773. [Google Scholar] [CrossRef]
- Lefevre, P.L.C.; Casteele, N.V. Clinical Pharmacology of Janus Kinase Inhibitors in Inflammatory Bowel Disease. J. Crohn’s Colitis 2020, 14 (Suppl. S2), S725–S736. [Google Scholar] [CrossRef] [PubMed]
- Mohamed, M.F.; Camp, H.S.; Jiang, P.; Padley, R.J.; Asatryan, A.; Othman, A.A. Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. Clin. Pharmacokinet. 2016, 55, 1547–1558. [Google Scholar] [CrossRef] [PubMed]
- Mukherjee, A.; Tsuchiwata, S.; Nicholas, T.; Cook, J.A.; Modesto, I.; Su, C.; D’Haens, G.R.; Sandborn, W.J. Exposure-Response Characterization of Tofacitinib Efficacy in Moderate to Severe Ulcerative Colitis: Results from Phase II and Phase III Induction and Maintenance Studies. Clin. Pharmacol. Ther. 2022, 112, 90–100. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Peyrin-Biroulet, L.; Sharara, A.I.; Su, C.; Modesto, I.; Mundayat, R.; Gunay, L.M.; Salese, L.; Sands, B.E. Efficacy and Safety of Tofacitinib in Ulcerative Colitis Based on Prior Tumor Necrosis Factor Inhibitor Failure Status. Clin. Gastroenterol. Hepatol. 2022, 20, 591–601.e8. [Google Scholar] [CrossRef] [PubMed]
- Dubinsky, M.C.; Peyrin-Biroulet, L.; Melmed, G.Y.; Hou, J.K.; Woodworth, D.A.; Friedman, G.S.; Zhang, H.; Maller, E.; Quirk, D.; Nduaka, C.I.; et al. Efficacy of Tofacitinib in Patients with Ulcerative Colitis by Prior Tumor Necrosis Factor Inhibitor Treatment Status: Results from OCTAVE Induction and Maintenance Studies: 640. Off. J. Am. Coll. Gastroenterol. ACG 2017, 112, S354. [Google Scholar] [CrossRef]
- Muensterman, E.; Engelhardt, B.; Gopalakrishnan, S.; Anderson, J.K.; Mohamed, M.F. Upadacitinib pharmacokinetics and exposure-response analyses of efficacy and safety in psoriatic arthritis patients—Analyses of phase III clinical trials. Clin. Transl. Sci. 2022, 15, 267–278. [Google Scholar] [CrossRef]
- Ponce-Bobadilla, A.V.; Stodtmann, S.; Eckert, D.; Zhou, W.; Liu, W.; Mohamed, M.F. Upadacitinib Population Pharmacokinetics and Exposure-Response Relationships in Ulcerative Colitis Patients. Clin. Pharmacokinet. 2023, 62, 101–112. [Google Scholar] [CrossRef]
- Vermeire, S.; Danese, S.; Zhou, W.; Klaff, J.; Ilo, D.; Yao, X.; Levy, G.; Higgins, P.D.R.; Loftus, E.V., Jr.; Panaccione, R. DOP41 Efficacy and safety of extended induction treatment with upadacitinib 45 mg once daily followed by maintenance upadacitinib 15 or 30 mg once daily in patients with moderately to severely active Ulcerative Colitis. J. Crohn’s Colitis 2022, 16 (Suppl. S1), i090–i091. [Google Scholar] [CrossRef]
- Meng, A.; Anderson, K.; Nelson, C.; Ni, L.; Chuang, S.M.; Bellanti, F.; Chang, P.; Comisar, C.; Kearney, B.P.; Bartok, B.; et al. Exposure-response relationships for the efficacy and safety of filgotinib and its metabolite GS-829845 in subjects with rheumatoid arthritis based on phase 2 and phase 3 studies. Br. J. Clin. Pharmacol. 2022, 88, 3211–3221. [Google Scholar] [CrossRef]
- Winthrop, K.L.; Cohen, S.B. Oral surveillance and JAK inhibitor safety: The theory of relativity. Nat. Rev. Rheumatol. 2022, 18, 301–304. [Google Scholar] [CrossRef]
- Sandborn, W.J.; Feagan, B.G.; D’Haens, G.; Wolf, D.C.; Jovanovic, I.; Hanauer, S.B.; Ghosh, S.; Petersen, A.; Hua, S.Y.; Lee, J.H.; et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 2021, 385, 1280–1291. [Google Scholar] [CrossRef]
- Danese, S.; Furfaro, F.; Vetrano, S. Targeting S1P in Inflammatory Bowel Disease: New Avenues for Modulating Intestinal Leukocyte Migration. J. Crohn’s Colitis 2018, 12 (Suppl. S2), S678–S686. [Google Scholar] [CrossRef]
- Surapaneni, S.; Yerramilli, U.; Bai, A.; Dalvie, D.; Brooks, J.; Wang, X.; Selkirk, J.V.; Yan, Y.G.; Zhang, P.; Hargreaves, R.; et al. Absorption, Metabolism, and Excretion, In Vitro Pharmacology, and Clinical Pharmacokinetics of Ozanimod, a Novel Sphingosine 1-Phosphate Receptor Modulator. Drug Metab. Dispos. 2021, 49, 405–419. [Google Scholar] [CrossRef]
- Sands, B.E.; Schreiber, S.; Blumenstein, I.; Chiorean, M.V.; Ungaro, R.C.; Rubin, D.T. Clinician’s Guide to Using Ozanimod for the Treatment of Ulcerative Colitis. J. Crohn’s Colitis 2023, 17, 2012–2025. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Tatosian, D.; Sid-Otmane, L.; Teuscher, N.; Chen, L.; Zhang, P.; Tirucherai, G.; Chitkara, D.; Marta, C. Population Pharmacokinetics of Ozanimod and Active Metabolite CC112273 in Patients with Ulcerative Colitis. Inflamm. Bowel Dis. 2022, 28 (Suppl. S1), S17–S18. [Google Scholar] [CrossRef]
- Tran, J.Q.; Zhang, P.; Walker, S.; Ghosh, A.; Syto, M.; Wang, X.; Harris, S.; Palmisano, M. Multiple-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites and the Pharmacodynamic and Pharmacokinetic Interactions with Pseudoephedrine, a Sympathomimetic Agent, in Healthy Subjects. Adv. Ther. 2020, 37, 4944–4958. [Google Scholar] [CrossRef]
- Torres, J.; Bonovas, S.; Doherty, G.; Kucharzik, T.; Gisbert, J.P.; Raine, T.; Adamina, M.; Armuzzi, A.; Bachmann, O.; Bager, P.; et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J. Crohn’s Colitis 2019, 14, 4–22. [Google Scholar] [CrossRef] [PubMed]
- Raine, T.; Bonovas, S.; Burisch, J.; Kucharzik, T.; Adamina, M.; Annese, V.; Bachmann, O.; Bettenworth, D.; Chaparro, M.; Czuber-Dochan, W.; et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. J. Crohn’s Colitis 2021, 16, 2–17. [Google Scholar] [CrossRef] [PubMed]
- Feuerstein, J.D.; Nguyen, G.C.; Kupfer, S.S.; Falck-Ytter, Y.; Singh, S. American Gastroenterological Association Institute Guideline on Therapeutic Drug Monitoring in Inflammatory Bowel Disease. Gastroenterology 2017, 153, 827–834. [Google Scholar] [CrossRef]
Methodology of Testing | Positives | Negatives | |
---|---|---|---|
Enzyme-linked immunoassay (ELISA) | Uses antibodies to detect drug levels either via indirect or sandwich methodologies. Each method ultimately requires a specific antigen-bound antibody to detect the presence of the drug in serum samples. This is achieved via incubation, buffering and a coloured substrate solution being analysed via microplate reader. | Sensitive, specific and easy to use. Cost effective. | The presence of the drug in the serum can impact anti-drug antibody testing. |
Radioimmunoassay | Specific drug-related radioactive antigen-bound antibodies are added to a medium along with patient serum. This is then centrifuged, and a gamma counter is used to determine drug levels and the presence of ADAs. | Rapid, highly sensitive and specific. No interference with the drug in the serum when detecting anti-drug antibodies. | Produces radioactive waste. Limited shelf-life due to radioactive decay. |
Liquid-chromatography and mass spectrometry (LC-MS) | The patient serum sample is added to a dried blood spot card, dried, then removed and added to an internal standard solution and methanol base. The sample is then put through an extraction process through an ultrasonic bath and liquid extraction. The sample is dried and then undergoes mass spectrometry. | Sensitive and specific. | Time consuming. |
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Dutt, K.; Vasudevan, A. Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease. Medicina 2024, 60, 250. https://doi.org/10.3390/medicina60020250
Dutt K, Vasudevan A. Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease. Medicina. 2024; 60(2):250. https://doi.org/10.3390/medicina60020250
Chicago/Turabian StyleDutt, Krishneel, and Abhinav Vasudevan. 2024. "Therapeutic Drug Monitoring for Biologic and Small-Molecule Therapies for Inflammatory Bowel Disease" Medicina 60, no. 2: 250. https://doi.org/10.3390/medicina60020250