Personalized therapies in pediatric inflammatory and autoimmune diseases

Current Pharmaceutical Design

Volumn 18, Issue 35, 2012, Pages 5766-5775

  Stocco, Gabriele ^a,c   de Iudicibus, Sara ^b   Franca, Raffaella ^b   Addobbati, Riccardo ^b   Decorti, Giuliana ^c  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^b INSTITUTE FOR MATERNAL AND CHILD HEALTH IRCCS BURLO GAROFOLO   (Italy)

^c UNIVERSITY OF TRIESTE   (Italy)

Author keywords

Juvenile rheumatoid arthritis; Pediatric inflammatory bowel disease; Personalized therapy; Pharmacodynamics; Pharmacogenetics; Pharmacokinetics

Indexed keywords

AZATHIOPRINE; DRUG METABOLITE; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; MERCAPTOPURINE; MESALAZINE; METHOTREXATE;

CHILD; CROHN DISEASE; DNA POLYMORPHISM; DRUG CLEARANCE; DRUG DOSE REGIMEN; DRUG METABOLISM; DRUG WITHDRAWAL; ENTERITIS; ENZYME ACTIVITY; FLU LIKE SYNDROME; GENE EXPRESSION; GENETIC MARKER; GENOTYPE; HIGH RISK PATIENT; HUMAN; JUVENILE RHEUMATOID ARTHRITIS; LYMPHOMA; PANCREATITIS; PERSONALIZED MEDICINE; PHARMACOGENETICS; PRIORITY JOURNAL; RASH; REVIEW; RISK REDUCTION; STEROID THERAPY; TREATMENT FAILURE; TREATMENT RESPONSE; ULCERATIVE COLITIS;

ARTHRITIS, RHEUMATOID; AUTOIMMUNE DISEASES; CHILD; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNOGENETIC PHENOMENA; INDIVIDUALIZED MEDICINE; INFLAMMATION; INFLAMMATORY BOWEL DISEASES; PHARMACOGENETICS;

EID: 84870229919     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803530853     Document Type: Review

References (108)

1. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis 2010; 17: 423-39.
2. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361: 2066-78.
3. Edison JD, Gilliland WR. Optimizing therapeutics: the next front in the war on rheumatoid arthritis. Clin Pharmacol Ther 2012; 91: 561-6.
4. Evans WE, Relling MV. Moving towards individualized medicine with pharmacogenomics. Nature 2004; 429: 464-8.
5. Feero WG, Guttmacher AE, Collins FS. Genomic medicine-an updated primer. N Engl J Med 2010; 362: 2001-11.
6. Relling MV, Altman RB, Goetz MP, Evans WE. Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism. Lancet Oncol 2010; 11: 507-9.
7. Stocco G, Crews KR. Pharmacogenetics, cost of genotyping, and guidelines for individualizing therapy with mercaptopurine in pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 2011; 57: 1247.
8. Den Boer ML, van Slegtenhorst M, De Menezes RX, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009; 10: 125-34.
9. Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med 2009; 360: 790-800.
10. Holleman A, Cheok MH, den Boer ML, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med 2004; 351: 533-42.
11. Burton ME, Shaw LM, Schentag JJ, Evans WE. Applied Pharmacokinetics and Pharmacodynamics: Principles of Therapeutic Drug Monitoring 2005.
12. Hearing SD, Norman M, Probert CS, Haslam N, Dayan CM. Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes. Gut 1999; 45: 382-8.
13. Cuzzoni E, De Iudicibus S, Bartoli F, Ventura A, Decorti G. Association between BclI polymorphism in the NR3C1 gene and in vitro individual variations in lymphocyte responses to methylprednisolone. Br J Clin Pharmacol 2012; 73: 651-5.
14. Becker ML. Optimization of pediatric rheumatology therapeutics. Clin Pharmacol Ther 2012; 91: 597-606.
15. Savage WJ, Everett AD. Biomarkers in pediatrics: children as biomarker orphans. Proteomics Clin Appl 2010; 4: 915-21.
16. De Iudicibus S, Franca R, Martelossi S, Ventura A, Decorti G. Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease. World J Gastroenterol 2011; 17: 1095-108.
17. De Iudicibus S, Stocco G, Martelossi S, et al. Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases. J Clin Gastroenterol 2011; 45: e1-7.
18. Maltese P, Palma L, Sfara C, et al. Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms. Pharmacogenomics J, 2011. doi: 10.1038/tpj.2011.26. [Epub ahead of print]
19. Cucchiara S, Latiano A, Palmieri O, et al. Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases. J Pediatr Gastroenterol Nutr 2007; 44: 171-9.
20. Jin Y, Mailloux CM, Gowan K, et al. NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med 2007; 356: 1216-25.
21. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P- glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97: 3473-8.
22. Cascorbi I, Gerloff T, Johne A, et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 2001; 69: 169-74.
23. Potocnik U, Ferkolj I, Glavac D, Dean M. Polymorphisms in multidrug resistance 1 (MDR1) gene are associated with refractory Crohn disease and ulcerative colitis. Genes Immun 2004; 5: 530-9.
24. Palmieri O, Latiano A, Valvano R, et al. Multidrug resistance 1 gene polymorphisms are not associated with inflammatory bowel disease and response to therapy in Italian patients. Aliment Pharmacol Ther 2005; 22: 1129-38.
25. Hearing SD, Norman M, Smyth C, Foy C, Dayan CM. Wide variation in lymphocyte steroid sensitivity among healthy human volunteers. J Clin Endocrinol Metab 1999; 84: 4149-54.
26. De Iudicibus S, Stocco G, Martelossi S, et al. Association of BclI polymorphism of the glucocorticoid receptor gene locus with response to glucocorticoids in inflammatory bowel disease. Gut 2007; 56: 1319-20.
27. Kirkham BW, Corkill MM, Davison SC, Panayi GS. Response to glucocorticoid treatment in rheumatoid arthritis: in vitro cell mediated immune assay predicts in vivo responses. J Rheumatol 1991; 18: 821-5.
28. Sliwinska-Stanczyk P, Pazdur J, Ziolkowska M, Jaworski J, Kaminska-Tchorzewska E, Lacki JK. The effect of methylprednisolone on proliferation of PBMCs obtained from steroid-sensitive and steroid-resistant rheumatoid arthritis patients. Scand J Rheumatol 2007; 36: 167-71.
29. Seki M, Ushiyama C, Seta N, et al. Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41: 823-30.
30. Hirano T, Homma M, Oka K, Tsushima H, Niitsuma T, Hayashi T. Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids. Immunopharmacology 1998; 40: 57-66.
31. Corrigan CJ, Brown PH, Barnes NC, et al. Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis 1991; 144: 1016-25.
32. Corrigan CJ, Bungre JK, Assoufi B, Cooper AE, Seddon H, Kay AB. Glucocorticoid resistant asthma: T-lymphocyte steroid metabolism and sensitivity to glucocorticoids and immunosuppressive agents. Eur Respir J 1996; 9: 2077-86.
33. Poznansky MC, Gordon AC, Douglas JG, Krajewski AS, Wyllie AH, Grant IW. Resistance to methylprednisolone in cultures of blood mononuclear cells from glucocorticoid-resistant asthmatic patients. Clin Sci 1984; 67: 639-45.
34. Langhoff E, Ladefoged J, Jakobsen BK, et al. Recipient lymphocyte sensitivity to methylprednisolone affects cadaver kidney graft survival. Lancet 1986; 1: 1296-7.
35. Hirano T, Akashi T, Kido T, Oka K, Shiratori T, Miyaoka M. Immunosuppressant pharmacodynamics on peripheral-blood mononuclear cells from patients with ulcerative colitis. Int Immunopharmacol 2002; 2: 1055-63.
36. Prefontaine E, Macdonald JK, Sutherland LR. Azathioprine or 6- mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2010; CD000545.
37. Grossman AB, Noble AJ, Mamula P, Baldassano RN. Increased dosing requirements for 6-mercaptopurine and azathioprine in inflammatory bowel disease patients six years and younger. Inflamm Bowel Dis 2008; 14: 750-5.
38. Zaza G, Cheok M, Krynetskaia N, et al. Thiopurine pathway. Pharmacogenet Genomics 2010; 20: 573-4.
39. Stocco G, Martelossi S, Barabino A, et al. TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. Dig Liver Dis 2005; 37: 940-5.
40. Relling MV, Gardner EE, Sandborn WJ, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011; 89: 387-91.
41. Colombel JF, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000; 118: 1025-30.
42. Stanulla M, Schaeffeler E, Flohr T, et al. Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA 2005; 293: 1485-9.
43. Relling MV, Hancock ML, Rivera GK, et al. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S- methyltransferase gene locus. J Natl Cancer Inst 1999; 91: 2001-8.
44. Serpe L, Calvo PL, Muntoni E, et al. Thiopurine S- methyltransferase pharmacogenetics in a large-scale healthy Italian-Caucasian population: differences in enzyme activity Pharmacogenomics 2009; 10: 1753-65.
45. Stocco G, De Iudicibus S; Cuzzoni E, Decorti G, Martelossi S, Ventura A. Letter: TPMT activity and age in IBD patients. Aliment Pharmacol Ther 2012; 35: 966-7; author reply 967-9.
46. Marsh S, Van Booven DJ. The increasing complexity of mercaptopurine pharmacogenomics. Clin Pharmacol Ther 2009; 85: 139-41.
47. Stocco G, Crews KR, Evans WE. Genetic polymorphism of inosine-triphosphate-pyrophosphatase influences mercaptopurine metabolism and toxicity during treatment of acute lymphoblastic leukemia individualized for thiopurine-S-methyl-transferase status. Expert Opin Drug Saf 2010; 9: 23-37.
48. Waisertreiger IS, Menezes MR, Randazzo J, Pavlov YI. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant. J Nucleic Acids 2010; 2010: pii: 872180.
49. Marinaki AM, Ansari A, Duley JA, et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics 2004; 14: 181-7.
50. von Ahsen N, Armstrong VW, Behrens C, et al. Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study. Clin Chem 2005; 51: 2282-8.
51. Zelinkova Z, Derijks LJ, Stokkers PC, et al. Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression. Clin Gastroenterol Hepatol 2006; 4: 44-9.
52. Ansari A, Arenas M, Greenfield SM, et al. Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Aliment Pharmacol Ther 2008; 28: 973-83.
53. Uchiyama K, Nakamura M, Kubota T, Yamane T, Fujise K, Tajiri H. Thiopurine S-methyltransferase and inosine triphosphate pyrophosphohydrolase genes in Japanese patients with inflammatory bowel disease in whom adverse drug reactions were induced by azathioprine/6-mercaptopurine treatment. J Gastroenterol 2009; 44: 197-203.
54. Zabala-Fernandez W, Barreiro-de Acosta M, Echarri A, et al. A pharmacogenetics study of TPMT and ITPA genes detects a relationship with side effects and clinical response in patients with inflammatory bowel disease receiving Azathioprine. J Gastrointestin Liver Dis 2011; 20: 247-53.
55. Shipkova M, Franz J, Abe M, Klett C, Wieland E, Andus T. Association between adverse effects under azathioprine therapy and inosine triphosphate pyrophosphatase activity in patients with chronic inflammatory bowel disease. Ther Drug Monit 2011; 33: 321-8.
56. Gearry RB, Roberts RL, Barclay ML, Kennedy MA. Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine. Pharmacogenetics 2004; 14: 779-81.
57. Allorge D, Hamdan R, Broly F, Libersa C, Colombel JF. ITPA genotyping test does not improve detection of Crohn's disease patients at risk of azathioprine/6-mercaptopurine induced myelosuppression. Gut 2005; 54: 565.
58. van Dieren JM, van Vuuren AJ, Kusters JG, Nieuwenhuis EE, Kuipers EJ, van der Woude CJ. ITPA genotyping is not predictive for the development of side effects in AZA treated inflammatory bowel disease patients. Gut 2005; 54: 1664.
59. De Ridder L, Van Dieren JM, Van Deventer HJ, et al. Pharmacogenetics of thiopurine therapy in paediatric IBD patient. Aliment Pharmacol Ther 2006; 23: 1137-41.
60. Hindorf U, Lindqvist M, Peterson C, et al. Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease. Gut 2006; 55: 1423-31.
61. Kim JH, Cheon JH, Hong SS, et al. Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. J Clin Gastroenterol 2010; 44: e242-8.
62. Stocco G, Cheok MH, Crews KR, et al. Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. Clin Pharmacol Ther 2009; 85: 164-72.
63. Adam de Beaumais T, Fakhoury M, Medard Y, et al. Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy. Br J Clin Pharmacol 2011; 71: 575-84.
64. Bennett LL Jr, Allan PW. Formation and significance of 6- methylthiopurine ribonucleotide as a metabolite of 6- mercaptopurine. Cancer Res 1971; 31: 152-8.
65. Dubinsky MC, Lamothe S, Yang HY, et al. Pharmacogenomics and metabolite measurement for 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705-13.
66. Hofmann U, Heinkele G, Angelberger S, et al. Simultaneous quantification of eleven thiopurine nucleotides by liquid chromatography-tandem mass spectrometry. Anal Chem 2012; 84: 1294-301.
67. Teichgraber U, Atreya I, Atreya R, Schwab M, Neurath MF. Infliximab treatment induces levels of the active azathioprine metabolite TGTP in Crohn's disease. Inflamm Bowel Dis 2012. doi: 10.1002/ibd.22998. [Epub ahead of print]
68. Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database 2010; baq020.
69. Eklund BI, Moberg M, Bergquist J, Mannervik B. Divergent activities of human glutathione transferases in the bioactivation of azathioprine. Mol Pharmacol 2006; 70: 747-54.
70. Eklund BI, Gunnarsdottir S, Elfarra AA, Mannervik B. Human glutathione transferases catalyzing the bioactivation of anticancer thiopurine prodrugs. Biochem Pharmacol 2007; 73: 1829-41.
71. Stocco G, Martelossi S, Barabino A, et al. TPMT genotype and the use of thiopurines in paediatric inflammatory bowel disease. Inflamm Bowel Dis 2007; 13: 57-64.
72. Smith M, Marinaki AM, Arenas M, et al. Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease. Aliment Pharmacol Ther 2009; 30: 375-84.
73. Haglund S, Taipalensuu J, Peterson C, Almer S. IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - relation to TPMT activity and metabolite concentrations. Br J Clin Pharmacol 2008; 65: 69-77.
74. Roberts RL, Gearry RB, Barclay ML, Kennedy MA. IMPDH1 promoter mutations in a patient exhibiting azathioprine resistance. Pharmacogenomics J 2007; 7: 312-7.
75. Diouf B, Cheng Q, Krynetskaia NF, et al. Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells. Nat Med 2011; 17: 1298-303.
76. Chalastanis A, Penard-Lacronique V, Svrcek M, et al. Azathioprine-induced carcinogenesis in mice according to Msh2 genotype. J Natl Cancer Inst 2010; 102: 1731-40.
77. Chouchana L, Narjoz C, Beaune P, Loriot MA, Roblin X. Azathioprine-induced carcinogenesis in mice according to Msh2 genotype. Aliment Pharmacol Ther 2012; 35: 15-36.
78. Stocco G, Londero M, Campanozzi A, et al. Usefulness of the measurement of azathioprine metabolites in the assessment of non- adherence. J Crohns Colitis 2010; 4: 599-602.
79. Hommel KA, Davis CM, Baldassano RN. Objective versus subjective assessment of oral medication adherence in pediatric inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 589-93.
80. Osterman MT, Kundu R, Lichtenstein GR, Lewis JD. Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis. Gastroenterology 2006; 130: 1047-53.
81. Gearry RB, Barclay ML. Azathioprine and 6-mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease. J Gastroenterol Hepatol 2005; 20: 1149-57.
82. Tremaine WJ. Failure to yield: drug resistance in inflammatory bowel disease. Gastroenterology 2002; 122: 1165-7.
83. Dubinsky MC, Yang H, Hassard PV, et al. 6-MP metabolite profiles provide a biochemical explanation for 6-MP resistance in patients with inflammatory bowel disease. Gastroenterology 2002; 122: 904-15.
84. Beaugerie L, Brousse N, Bouvier AM, et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009; 374: 1617-25.
85. Vos AC, Bakkal N, Minnee RC, et al. Risk of malignant lymphoma in patients with inflammatory bowel diseases: a Dutch nationwide study. Inflamm Bowel Dis 2011; 17: 1837-45.
86. Beigel F, Jurgens M, Tillack C, et al. Hepatosplenic T-cell lymphoma in a patient with Crohn's disease. Nat Rev Gastroenterol Hepatol 2009; 6: 433-6.
87. van Schaik FD, van Oijen MG, Smeets HM, van der Heijden GJ, Siersema PD, Oldenburg B. Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease. Gut 2012; 61: 235-40.
88. Stocco G, Martelossi S, Malusa' N, et al. Interruption of mesalamine and reduction of the blood concentration of the active metabolites of azathioprine: possible causes of ulcerative colitis relapse. Dig Dis Sci 2008; 53: 3246-9.
89. Xin H, Fischer C, Schwab M, Klotz U. Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex vivo study in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2005; 21: 1105-9.
90. Butcher NJ, Minchin RF. Arylamine N-acetyltransferase 1: a novel drug target in cancer development. Pharmacol Rev 2012; 64: 147-65.
91. Sim E, Lack N, Wang CJ, et al. Arylamine N-acetyltransferases: structural and functional implications of polymorphisms. Toxicology 2008; 254: 170-83.
92. Huang YS, Chern HD, Su WJ, et al. Arylamine N- acetyltransferases: structural and functional implications of polymorphisms. Hepatology 2002; 35: 883-9.
93. Rieder MJ, Shear NH, Kanee A, Tang BK, Spielberg SP. Prominence of slow acetylator phenotype among patients with sulfonamide hypersensitivity reactions. Clin Pharmacol Ther 1991; 49: 13-7.
94. Wang D, Para MF, Koletar SL, Sadee W. Human N- acetyltransferase 1 *10 and *11 alleles increase protein expression through distinct mechanisms and associate with sulfamethoxazole- induced hypersensitivity. Pharmacogenet Genomics 2011; 21: 652-64.
95. Ricart E, Taylor WR, Loftus EV, et al. N-acetyltransferase 1 and 2 genotypes do not predict response or toxicity to treatment with mesalamine and sulfasalazine in patients with ulcerative colitis. Am J Gastroenterol 2002; 97: 1763-8.
96. Wakefield L, Boukouvala S, Sim E. Characterisation of CpG methylation in the upstream control region of mouse Nat2: evidence for a gene-environment interaction in a polymorphic gene implicated in folate metabolism. Gene 2010; 452: 16-21.
97. Giannini EH, Brewer EJ, Kuzmina N, et al. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.- U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. N Engl J Med 1992; 326: 1043-9.
98. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res 2011; 63: 465-82.
99. Cronstein BN, Naime D, Ostad E. The anti-inflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92: 2675-82.
100. Dervieux T, Furst D, Lein DO, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 2004; 50: 2766-74.
101. Mikkelsen TS, Thorn CF, Yang JJ, et al. PharmGKB summary: methotrexate pathway. Pharmacogenet Genomics 2011; 21: 679-86.
102. Hinks A, Moncrieffe H, Martin P, et al. Association of the 5- aminoimidazole-4-carboxamide ribonucleotide transformylase gene with response to methotrexate in juvenile idiopathic arthritis. Ann Rheum Dis 2011; 70: 1395-400.
103. Dervieux T, Wessels JA, Kremer JM, et al. Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. Pharmacogenet Genomics 2012; 22: 1-9.
104. Owen SA, Hider SL, Martin P, Bruce IN, Barton A, Thomson W. Genetic polymorphisms in key methotrexate pathway genes are associated with response to treatment in rheumatoid arthritis patients. Pharmacogenomics J, 2012. doi: 10.1038/tpj.2012.7. [Epub ahead of print]
105. Evans WE, Crom WR, Stewart CF, et al. Methotrexate systemic clearance influences probability of relapse in children with standard-risk acute lymphocytic leukaemia. Lancet 1984; 1: 359-62.
106. Evans WE, Crom WR, Abromowitch M, et al. Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia. Identification of a relation between concentration and effect. N Engl J Med 1986; 314: 471-7.
107. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 1998; 338: 499-505.
108. Becker ML, Gaedigk R, van Haandel L, et al. Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations. Arthritis Rheum 2010; 63: 276-85.