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Erschienen in: Current Gastroenterology Reports 5/2018

01.05.2018 | Pediatric Gastroenterology (S Orenstein, Section Editor)

Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

verfasst von: Nicholas Carman, David R. Mack, Eric I. Benchimol

Erschienen in: Current Gastroenterology Reports | Ausgabe 5/2018

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Abstract

Purpose of review

Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD.

Recent findings

Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing “reactive” monitoring and “proactive” monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility.

Summary

The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.
Literatur
19.
Zurück zum Zitat D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London position statement of the world congress of gastroenterology on biological therapy for IBD with the European Crohn’s and colitis organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol. 2011;106(2):199–212; quiz 3. https://doi.org/10.1038/ajg.2010.392.PubMedCrossRef D'Haens GR, Panaccione R, Higgins PD, Vermeire S, Gassull M, Chowers Y, et al. The London position statement of the world congress of gastroenterology on biological therapy for IBD with the European Crohn’s and colitis organization: when to start, when to stop, which drug to choose, and how to predict response? Am J Gastroenterol. 2011;106(2):199–212; quiz 3. https://​doi.​org/​10.​1038/​ajg.​2010.​392.PubMedCrossRef
21.
Zurück zum Zitat Dreesen E, Van Stappen T, Ballet V, Peeters M, Compernolle G, Tops S, et al. Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn’s disease who lose clinical response. Aliment Pharmacol Ther. 2018;47(3):346–55. https://doi.org/10.1111/apt.14452.PubMedCrossRef Dreesen E, Van Stappen T, Ballet V, Peeters M, Compernolle G, Tops S, et al. Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn’s disease who lose clinical response. Aliment Pharmacol Ther. 2018;47(3):346–55. https://​doi.​org/​10.​1111/​apt.​14452.PubMedCrossRef
25.
Zurück zum Zitat Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118(6):1025–30.PubMedCrossRef Colombel JF, Ferrari N, Debuysere H, Marteau P, Gendre JP, Bonaz B, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology. 2000;118(6):1025–30.PubMedCrossRef
26.
Zurück zum Zitat Dubinsky MC. Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004;2(9):731–43.PubMedCrossRef Dubinsky MC. Azathioprine, 6-mercaptopurine in inflammatory bowel disease: pharmacology, efficacy, and safety. Clin Gastroenterol Hepatol. 2004;2(9):731–43.PubMedCrossRef
35.
Zurück zum Zitat Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000;118(4):705–13.PubMedCrossRef Dubinsky MC, Lamothe S, Yang HY, Targan SR, Sinnett D, Theoret Y, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology. 2000;118(4):705–13.PubMedCrossRef
36.
Zurück zum Zitat Dubinsky MC, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology. 2002;122(4):904–15.PubMedCrossRef Dubinsky MC, Yang H, Hassard PV, Seidman EG, Kam LY, Abreu MT, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology. 2002;122(4):904–15.PubMedCrossRef
37.
Zurück zum Zitat Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 1980;32(5):651–62.PubMedPubMedCentral Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 1980;32(5):651–62.PubMedPubMedCentral
39.
Zurück zum Zitat •• Lee MN, Kang B, Choi SY, Kim MJ, Woo SY, Kim JW, et al. Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and therapeutic response in pediatric patients with IBD treated with azathioprine. Inflamm Bowel Dis. 2015;21(5):1054–62. https://doi.org/10.1097/mib.0000000000000347. Relationship between 6TGN levels and clinical outcome for azathioprine in Pediatric IBD. PubMedCrossRef •• Lee MN, Kang B, Choi SY, Kim MJ, Woo SY, Kim JW, et al. Relationship between azathioprine dosage, 6-thioguanine nucleotide levels, and therapeutic response in pediatric patients with IBD treated with azathioprine. Inflamm Bowel Dis. 2015;21(5):1054–62. https://​doi.​org/​10.​1097/​mib.​0000000000000347​. Relationship between 6TGN levels and clinical outcome for azathioprine in Pediatric IBD. PubMedCrossRef
44.
Zurück zum Zitat Kariyawasam VC, Ward MG, Blaker PA, Patel KV, Goel R, Sanderson JD, et al. Thiopurines dosed to a therapeutic 6-Thioguanine level in combination with adalimumab are more effective than subtherapeutic thiopurine-based combination therapy or adalimumab monotherapy during induction and maintenance in patients with long-standing Crohn’s disease. Inflamm Bowel Dis. 2017;23(9):1555–65. https://doi.org/10.1097/mib.0000000000001183.PubMedCrossRef Kariyawasam VC, Ward MG, Blaker PA, Patel KV, Goel R, Sanderson JD, et al. Thiopurines dosed to a therapeutic 6-Thioguanine level in combination with adalimumab are more effective than subtherapeutic thiopurine-based combination therapy or adalimumab monotherapy during induction and maintenance in patients with long-standing Crohn’s disease. Inflamm Bowel Dis. 2017;23(9):1555–65. https://​doi.​org/​10.​1097/​mib.​0000000000001183​.PubMedCrossRef
46.
55.
Zurück zum Zitat Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM. Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther. 2010;48(5):297–308.PubMedCrossRef Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM. Serum albumin concentration: a predictive factor of infliximab pharmacokinetics and clinical response in patients with ulcerative colitis. Int J Clin Pharmacol Ther. 2010;48(5):297–308.PubMedCrossRef
57.
Zurück zum Zitat 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. 2017:gutjnl-2016-313071. https://doi.org/10.1136/gutjnl-2016-313071. 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. 2017:gutjnl-2016-313071. https://​doi.​org/​10.​1136/​gutjnl-2016-313071.
58.
Zurück zum Zitat •• Adedokun OJ, Xu Z, Padgett L, Blank M, Johanns J, Griffiths A, et al. Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase 3 study. Inflamm Bowel Dis. 2013;19(13):2753–62. https://doi.org/10.1097/01.MIB.0000435438.84365.f7. Relationship between IFX trough levels and clinical outcome in Pediatric UC. PubMedCrossRef •• Adedokun OJ, Xu Z, Padgett L, Blank M, Johanns J, Griffiths A, et al. Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase 3 study. Inflamm Bowel Dis. 2013;19(13):2753–62. https://​doi.​org/​10.​1097/​01.​MIB.​0000435438.​84365.​f7. Relationship between IFX trough levels and clinical outcome in Pediatric UC. PubMedCrossRef
61.
Zurück zum Zitat Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Ainsworth MA. Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn’s disease: post hoc analysis of a randomized controlled trial. Am J Gastroenterol. 2014;109(7):1055–64. https://doi.org/10.1038/ajg.2014.106.PubMedCrossRef Steenholdt C, Bendtzen K, Brynskov J, Thomsen OO, Ainsworth MA. Clinical implications of measuring drug and anti-drug antibodies by different assays when optimizing infliximab treatment failure in Crohn’s disease: post hoc analysis of a randomized controlled trial. Am J Gastroenterol. 2014;109(7):1055–64. https://​doi.​org/​10.​1038/​ajg.​2014.​106.PubMedCrossRef
62.
Zurück zum Zitat Gardiner KR, Halliday MI, Barclay GR, Milne L, Brown D, Stephens S, et al. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut. 1995;36(6):897–901.PubMedPubMedCentralCrossRef Gardiner KR, Halliday MI, Barclay GR, Milne L, Brown D, Stephens S, et al. Significance of systemic endotoxaemia in inflammatory bowel disease. Gut. 1995;36(6):897–901.PubMedPubMedCentralCrossRef
66.
Zurück zum Zitat • Falaiye TO, Mitchell KR, Lu Z, Saville BR, Horst SN, Moulton DE, et al. Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD. J Pediatr Gastroenterol Nutr. 2014;58(2):213–9. https://doi.org/10.1097/MPG.0b013e3182a98df2. Relationship between infliximab trough levels and infliximab failure in Pediatric IBD. PubMedCrossRef • Falaiye TO, Mitchell KR, Lu Z, Saville BR, Horst SN, Moulton DE, et al. Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD. J Pediatr Gastroenterol Nutr. 2014;58(2):213–9. https://​doi.​org/​10.​1097/​MPG.​0b013e3182a98df2​. Relationship between infliximab trough levels and infliximab failure in Pediatric IBD. PubMedCrossRef
70.
Zurück zum Zitat •• Choi SY, Kang B, Lee JH, Choe YH. Clinical use of measuring trough levels and antibodies against infliximab in patients with pediatric inflammatory bowel disease. Gut Liver. 2017;11(1):55–61. https://doi.org/10.5009/gnl16041. Relationship between infliximab trough levels, ADAs and clinical outcome in Pediatric IBD. PubMedCrossRef •• Choi SY, Kang B, Lee JH, Choe YH. Clinical use of measuring trough levels and antibodies against infliximab in patients with pediatric inflammatory bowel disease. Gut Liver. 2017;11(1):55–61. https://​doi.​org/​10.​5009/​gnl16041. Relationship between infliximab trough levels, ADAs and clinical outcome in Pediatric IBD. PubMedCrossRef
71.
Zurück zum Zitat •• Merras-Salmio L, Kolho KL. Clinical use of infliximab trough levels and antibodies to infliximab in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2017;64(2, 272):–8. https://doi.org/10.1097/mpg.0000000000001258. Relationship between infliximab trough levels, ADAs and clinical outcome in Pediatric IBD. •• Merras-Salmio L, Kolho KL. Clinical use of infliximab trough levels and antibodies to infliximab in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2017;64(2, 272):–8. https://​doi.​org/​10.​1097/​mpg.​0000000000001258​. Relationship between infliximab trough levels, ADAs and clinical outcome in Pediatric IBD.
72.
Zurück zum Zitat • Deora V, Kozak J, El-Kalla M, Huynh HQ, El-Matary W. Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease. Acta Paediatr. 2017;106(11):1863–7. https://doi.org/10.1111/apa.14008. Use of TDM to guide clinical decision making for infliximab in Pediatric IBD. PubMedCrossRef • Deora V, Kozak J, El-Kalla M, Huynh HQ, El-Matary W. Therapeutic drug monitoring was helpful in guiding the decision-making process for children receiving infliximab for inflammatory bowel disease. Acta Paediatr. 2017;106(11):1863–7. https://​doi.​org/​10.​1111/​apa.​14008. Use of TDM to guide clinical decision making for infliximab in Pediatric IBD. PubMedCrossRef
73.
Zurück zum Zitat • Frymoyer A, Hoekman DR, Piester TL, de Meij TG, Hummel TZ, Benninga MA, et al. Application of population pharmacokinetic modeling for individualized infliximab dosing strategies in Crohn Disease. J Pediatr Gastroenterol Nutr. 2017;65(6):639–45. https://doi.org/10.1097/mpg.0000000000001620. Use of population PK to predict infliximab trough levels in Pediatric CD. PubMedCrossRef • Frymoyer A, Hoekman DR, Piester TL, de Meij TG, Hummel TZ, Benninga MA, et al. Application of population pharmacokinetic modeling for individualized infliximab dosing strategies in Crohn Disease. J Pediatr Gastroenterol Nutr. 2017;65(6):639–45. https://​doi.​org/​10.​1097/​mpg.​0000000000001620​. Use of population PK to predict infliximab trough levels in Pediatric CD. PubMedCrossRef
75.
Zurück zum Zitat •• Hoekman DR, Brandse JF, de Meij TG, Hummel TZ, Lowenberg M, Benninga MA, et al. The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease. Scand J Gastroenterol. 2015;50(9):1110–7. https://doi.org/10.3109/00365521.2015.1027264. Relationship between maintenance infliximab trough levels and clinical outcome in Pediatric IBD. PubMedCrossRef •• Hoekman DR, Brandse JF, de Meij TG, Hummel TZ, Lowenberg M, Benninga MA, et al. The association of infliximab trough levels with disease activity in pediatric inflammatory bowel disease. Scand J Gastroenterol. 2015;50(9):1110–7. https://​doi.​org/​10.​3109/​00365521.​2015.​1027264. Relationship between maintenance infliximab trough levels and clinical outcome in Pediatric IBD. PubMedCrossRef
76.
78.
Zurück zum Zitat •• Rolandsdotter H, Marits P, Sundin U, Wikstrom AC, Fagerberg UL, Finkel Y, et al. Serum-infliximab trough levels in 45 children with inflammatory bowel disease on maintenance treatment. Int J Mol Sci. 2017;18(3) https://doi.org/10.3390/ijms18030575. Relationship between maintenance infliximab trough levels and clinical outcome in Pediatric IBD. •• Rolandsdotter H, Marits P, Sundin U, Wikstrom AC, Fagerberg UL, Finkel Y, et al. Serum-infliximab trough levels in 45 children with inflammatory bowel disease on maintenance treatment. Int J Mol Sci. 2017;18(3) https://​doi.​org/​10.​3390/​ijms18030575. Relationship between maintenance infliximab trough levels and clinical outcome in Pediatric IBD.
79.
Zurück zum Zitat •• Singh N, Rosenthal CJ, Melmed GY, Mirocha J, Farrior S, Callejas S, et al. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014;20(10):1708–13. https://doi.org/10.1097/mib.0000000000000137. Relationship between post induction infliximab trough levels and clinical outcome in Pediatric IBD. PubMedCrossRef •• Singh N, Rosenthal CJ, Melmed GY, Mirocha J, Farrior S, Callejas S, et al. Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2014;20(10):1708–13. https://​doi.​org/​10.​1097/​mib.​0000000000000137​. Relationship between post induction infliximab trough levels and clinical outcome in Pediatric IBD. PubMedCrossRef
80.
Zurück zum Zitat • Stein R, Lee D, Leonard MB, Thayu M, Denson LA, Chuang E, et al. Serum infliximab, antidrug antibodies, and tumor necrosis factor predict sustained response in pediatric Crohn’s disease. Inflamm Bowel Dis. 2016;22(6):1370–7. https://doi.org/10.1097/mib.0000000000000769. Relationship between post induction infliximab trough levels and infliximab continuation in Pediatric CD. PubMedCrossRef • Stein R, Lee D, Leonard MB, Thayu M, Denson LA, Chuang E, et al. Serum infliximab, antidrug antibodies, and tumor necrosis factor predict sustained response in pediatric Crohn’s disease. Inflamm Bowel Dis. 2016;22(6):1370–7. https://​doi.​org/​10.​1097/​mib.​0000000000000769​. Relationship between post induction infliximab trough levels and infliximab continuation in Pediatric CD. PubMedCrossRef
83.
91.
Zurück zum Zitat Hanauer SB, Wagner CL, Bala M, Mayer L, Travers S, Diamond RH, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2(7):542–53.PubMedCrossRef Hanauer SB, Wagner CL, Bala M, Mayer L, Travers S, Diamond RH, et al. Incidence and importance of antibody responses to infliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2(7):542–53.PubMedCrossRef
92.
Zurück zum Zitat Drobne D, Bossuyt P, Breynaert C, Cattaert T, Vande Casteele N, Compernolle G, 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):514–21.e4. https://doi.org/10.1016/j.cgh.2014.07.027. Drobne D, Bossuyt P, Breynaert C, Cattaert T, Vande Casteele N, Compernolle G, 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):514–21.e4. https://​doi.​org/​10.​1016/​j.​cgh.​2014.​07.​027.
101.
Zurück zum Zitat Bodini G, Giannini EG, Savarino V, Del Nero L, Lo Pumo S, Brunacci M, et al. Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease. Dig Liver Dis. 2017; https://doi.org/10.1016/j.dld.2017.11.008. Bodini G, Giannini EG, Savarino V, Del Nero L, Lo Pumo S, Brunacci M, et al. Infliximab trough levels and persistent vs transient antibodies measured early after induction predict long-term clinical remission in patients with inflammatory bowel disease. Dig Liver Dis. 2017; https://​doi.​org/​10.​1016/​j.​dld.​2017.​11.​008.
103.
Zurück zum Zitat Crowley ECN, Mack DR, El-Matery W, Frost K, Arpino V, Benchimol EI, et al. Griffiths AM. Therapeutic drug monitoring during infiximab induction in paedaitric IBD: A multi-centre prospective cohort study. PIBD; 2017. p. 2017. Crowley ECN, Mack DR, El-Matery W, Frost K, Arpino V, Benchimol EI, et al. Griffiths AM. Therapeutic drug monitoring during infiximab induction in paedaitric IBD: A multi-centre prospective cohort study. PIBD; 2017. p. 2017.
105.
Zurück zum Zitat D'Haens G, Vermeire S, Lambrecht G, Baert F, Bossuyt P, Pariente B, et al. Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, or corticosteroid-free remission in patients with active luminal Crohn’s disease. Gastroenterology. 2018; https://doi.org/10.1053/j.gastro.2018.01.004. D'Haens G, Vermeire S, Lambrecht G, Baert F, Bossuyt P, Pariente B, et al. Increasing infliximab dose based on symptoms, biomarkers, and serum drug concentrations does not increase clinical, endoscopic, or corticosteroid-free remission in patients with active luminal Crohn’s disease. Gastroenterology. 2018; https://​doi.​org/​10.​1053/​j.​gastro.​2018.​01.​004.
108.
Zurück zum Zitat Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, 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(6):919–27. https://doi.org/10.1136/gutjnl-2013-305279.PubMedCrossRef Steenholdt C, Brynskov J, Thomsen OO, Munck LK, Fallingborg J, Christensen LA, 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(6):919–27. https://​doi.​org/​10.​1136/​gutjnl-2013-305279.PubMedCrossRef
110.
Zurück zum Zitat Roblin X, Attar A, Lamure M, Savarieau B, Brunel P, Duru G, et al. Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn’s disease patients who lose response to infliximab. J Mark Access Health Policy. 2015;3 https://doi.org/10.3402/jmahp.v3.29229. Roblin X, Attar A, Lamure M, Savarieau B, Brunel P, Duru G, et al. Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn’s disease patients who lose response to infliximab. J Mark Access Health Policy. 2015;3 https://​doi.​org/​10.​3402/​jmahp.​v3.​29229.
112.
114.
118.
121.
Zurück zum Zitat Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–84. https://doi.org/10.1016/s0140-6736(08)60726-6.PubMedCrossRef Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–84. https://​doi.​org/​10.​1016/​s0140-6736(08)60726-6.PubMedCrossRef
122.
Zurück zum Zitat Adedokun OJXZ, Gasink C, et al. Sa1934 pharmacokinetics and exposure response relationships of ustekinumab during IV induction and SC maintenance treatment of patients with Crohn’s disease with ustekinumab: results from the UNITI-1, UNITI-2 aand IM-UNITI studies. Gastroenterology. 2016;150(4):S408. Adedokun OJXZ, Gasink C, et al. Sa1934 pharmacokinetics and exposure response relationships of ustekinumab during IV induction and SC maintenance treatment of patients with Crohn’s disease with ustekinumab: results from the UNITI-1, UNITI-2 aand IM-UNITI studies. Gastroenterology. 2016;150(4):S408.
Metadaten
Titel
Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease
verfasst von
Nicholas Carman
David R. Mack
Eric I. Benchimol
Publikationsdatum
01.05.2018
Verlag
Springer US
Erschienen in
Current Gastroenterology Reports / Ausgabe 5/2018
Print ISSN: 1522-8037
Elektronische ISSN: 1534-312X
DOI
https://doi.org/10.1007/s11894-018-0623-z

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