Rational development and utilization of antibody-based therapeutic proteins in pediatrics

Pharmacology and Therapeutics

Volumn 137, Issue 2, 2013, Pages 225-247

  Xu, Zhenhua ^a   Davis, Hugh M ^a   Zhou, Honghui ^a  

^a JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

Dose optimization; Infliximab; Monoclonal antibodies; Pediatric; Pharmacodynamics; Pharmacokinetics; Rational therapy; Therapeutic proteins; Tumor necrosis factor alpha

Indexed keywords

ABATACEPT; ADALIMUMAB; ALEMTUZUMAB; BASILIXIMAB; BELATACEPT; BELIMUMAB; BEVACIZUMAB; BRIAKINUMAB; CANAKINUMAB; CERTOLIZUMAB PEGOL; DACLIZUMAB; DENOSUMAB; ECULIZUMAB; ETANERCEPT; GOLIMUMAB; INFLIXIMAB; IPILIMUMAB; IXEKIZUMAB; LEBRIKIZUMAB; MEPOLIZUMAB; MONOCLONAL ANTIBODY; OCRELIZUMAB; OMALIZUMAB; PAGIBAXIMAB; PALIVIZUMAB; RILONACEPT; RITUXIMAB; SIRUKUMAB; TOCILIZUMAB; UNINDEXED DRUG;

ALLOMETRY; AREA UNDER THE CURVE; ASTHMA; BACTERIAL INFECTION; BODY SURFACE; BODY WEIGHT; CINCA SYNDROME; CLINICAL EFFECTIVENESS; CLINICAL TRIAL (TOPIC); CROHN DISEASE; DOSE RESPONSE; DRUG ABSORPTION; DRUG APPROVAL; DRUG BINDING; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG ELIMINATION; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TARGETING; DRUG USE; EOSINOPHILIC ESOPHAGITIS; GLIOMA; GRANULOMATOSIS; HEMOLYTIC UREMIC SYNDROME; HUMAN; HYPEREOSINOPHILIC SYNDROME; IMMUNE RESPONSE; IMMUNOGENICITY; JUVENILE RHEUMATOID ARTHRITIS; KIDNEY GRAFT REJECTION; MELANOMA; MICROSCOPIC POLYANGIITIS; MULTIPLE SCLEROSIS; PEDIATRICS; PRIORITY JOURNAL; PSORIASIS VULGARIS; RESPIRATORY SYNCYTIAL VIRUS INFECTION; REVIEW; RHABDOMYOSARCOMA; SEPSIS; SIMULATION; SOLID TUMOR; SYSTEMIC LUPUS ERYTHEMATOSUS; TREATMENT INDICATION; ULCERATIVE COLITIS;

ADULT; ANTIBODIES, MONOCLONAL; CHILD; DRUG UTILIZATION; HUMANS; MOLECULAR TARGETED THERAPY; PEDIATRICS;

EID: 84872786443     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2012.10.005     Document Type: Review

References (177)

1. Abbott Laboratories Humira® US Prescribing Information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/125057s0276lbl.pdf 2011 Accessed July 6 2012
2. S.M. Abdel-Rahman, M.D. Reed, T.G. Wells, and G.L. Kearns Considerations in the rational design and conduct of phase I/II pediatric clinical trials: avoiding the problems and pitfalls Clin Pharmacol Ther 81 2007 483 494
3. Amgen, and Pfizer Enbrel® US prescribing information Available at http://pi.amgen.com/united-states/enbrel/derm/enbrel-pi.pdf 2011 Accessed July 6 2012
4. B.J. Anderson, and N.H. Holford Mechanism-based concepts of size and maturity in pharmacokinetics Annu Rev Pharmacol Toxicol 48 2008 303 332
5. G.D. Anderson, and A.M. Lynn Optimizing pediatric dosing: a developmental pharmacologic approach Pharmacotherapy 29 2009 680 690
6. S. Bai, K. Jorga, Y. Xin, D. Jin, Y. Zheng, and L.A. Damico-Beyer A guide to rational dosing of monoclonal antibodies Clin Pharmacokinet 51 2012 119 135
7. G.M. Bartelds, C.L. Krieckaert, M.T. Nurmohamed, P.A. van Schouwenburg, W.F. Lems, and J.W. Twisk Development of antidrug antibodies against adalimumab and association with disease activity and treatment failure during long-term follow-up JAMA 305 2011 1460 1468
8. D.K. Benjamin Jr., P.B. Smith, M.D. Murphy, R. Roberts, L. Mathis, and D. Avant Peer-reviewed publication of clinical trials completed for pediatric exclusivity JAMA 296 2006 1266 1273
9. T. Beukelman, N.M. Patkar, K.G. Saag, S. Tolleson-Rinehart, R.Q. Cron, and E.M. DeWitt 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 (Hoboken) 63 2011 465 482
10. Biomarkers Definitions Working Group Biomarkers and surrogate endpoints: preferred definitions and conceptual framework Clin Pharmacol Ther 69 2001 89 95
11. Bristol-Myers Squibb Company Orencia® US prescribing information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2012/ 125118s0138lbl.pdf 2012 Accessed July 6 2012
12. R. Bruno, C.B. Washington, J.F. Lu, G. Lieberman, L. Banken, and P. Klein Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic breast cancer Cancer Chemother Pharmacol 56 2005 361 369
13. A.M. Buchner, W. Blonski, and G.R. Lichtenstein Update on the management of Crohn's disease Curr Gastroenterol Rep 13 2011 465 474
14. P.J. Bugelski, and P.L. Martin Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets Br J Pharmacol 166 2012 823 846
15. J.C. Burns, B.M. Best, A. Mejias, L. Mahony, D.E. Fixler, and H.S. Jafri Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease Pediatrics 153 2008 833 838
16. W. Busse, S.P. Banks-Schlegel, and G.L. Larsen Childhood- versus adult-onset asthma Am J Respir Crit Care Med 151 1995 1635 1639
17. I.C. Büttel, P. Chamberlain, Y. Chowers, F. Ehmann, A. Greinacher, and R. Jefferis Taking immunogenicity assessment of therapeutic proteins to the next level Biologicals 39 2011 100 109
18. P.J. Carter Potent antibody therapeutics by design Nat Rev Immunol 6 2006 343 357
19. M. Cella, C. Knibbe, M. Danhof, and O. Della Pasqua What is the right dose for children? Br J Clin Pharmacol 70 2010 597 603
20. M. Cella, F. Gorter de Vries, D. Burger, M. Danhof, and O. Della Pasqua A model-based approach to dose selection in early pediatric development Clin Pharmacol Ther 87 2010 294 302
21. Centers for Disease Control CDC growth charts Available at http://www.cdc.gov/growthcharts/percentile-data-files.htm 2009 Accessed July 6 2012
22. R. Chaudhary, M. Butler, R.J. Playford, and S. Ghosh Anti-TNF antibody induced stimulated T lymphocyte apoptosis depends on the concentration of the antibody and etanercept induces apoptosis at rates equivalent to infliximab and adlimumab at 10 micrograms per ml concentration Gastroenterology 130 2006 A696
23. S.C. Chow, and M. Chang Adaptive design methods in clinical trials - a review Orphanet J Rare Dis 3 2008 11
24. M.S. Co, and C. Queen Humanized antibodies for therapy Nature 351 1991 501 502
25. J.F. Colombel, W.J. Sandborn, W. Reinisch, G.J. Mantzaris, A. Kornbluth, and D. Rachmilewitz Infliximab, azathioprine, or combination therapy for Crohn's disease N Engl J Med 362 2010 1383 1395
26. J.D. Crawford, M.E. Terry, and G.M. Rourke Simplification of drug dosage calculation by application of the surface area principle Pediatrics 5 1950 783 790
27. S. Cucchiara, and A. Morley-Fletcher "New drugs: kids come first": children should be included in trials of new biological treatments Inflamm Bowel Dis 13 2007 1165 1169
28. S. Cucchiara, J.C. Escher, H. Hildebrand, J. Amil-Dias, L. Stronati, and F.M. Ruemmele Pediatric inflammatory bowel diseases and the risk of lymphoma: should we revise our treatment strategies? J Pediatr Gastroenterol Nutr 48 2009 257 267
29. S.N. de Wildt, G.L. Kearns, J.S. Leeder, and J.N. van den Anker Glucuronidation in humans. Pharmacogenetic and developmental aspects Clin Pharmacokinet 36 1999 439 452
30. A.T. Derivan, B.L. Leventhal, J. March, M. Wolraich, and J.M. Zito The ethical use of placebo in clinical trials involving children J Child Adolesc Psychopharmacol 14 2004 169 174
31. G. D'Haens, F. Baert, G. van Assche, P. Caenepeel, P. Vergauwe, and H. Tuynman Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial Lancet 371 2008 660 667
32. N.L. Dirks, and B. Meibohm Population pharmacokinetics of therapeutic monoclonal antibodies Clin Pharmacokinet 49 2010 633 659
33. J. Dunne, W.J. Rodriguez, M.D. Murphy, B.N. Beasley, G.J. Burckart, and J.D. Filie Extrapolation of adult data and other data in pediatric drug-development programs Pediatrics 128 2011 e1242 e1249
34. EMA The EU pediatric regulation Available at http://www.emea.europa.eu/ htms/human/paediatrics/regulation.htm 2007 Accessed July 6 2012
35. EMA Assessment report for tocilizumab Type II variation EMEA/H/C/955/II/15 for systemic idiopathic juvenile arthritis Available at http://www.emea.europa.eu/docs/en-GB/document-library/EPAR--Assessment-Report-- Variation/human/000955/WC500111086.pdf 2011 Accessed July 6 2012
36. EMA Opinions and decisions on PIP applications Available at http://www.emea.europa.eu/htms/human/paediatrics/regulation.htm 2012 Accessed July 8 2012
37. EMA Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use Available at http://www.ema.europa.eu/docs/en- GB/document-library/Scientific-guideline/2012/06/WC500128688.pdf 2012 Accessed September 23, 2012
38. P. Emery, R. Fleischmann, D. van der Heijde, E.C. Keystone, M.C. Genovese, and P.G. Conaghan The effects of golimumab on radiographic progression in RA: results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy Arthritis Rheum 63 2011 1200 1210
39. N. Emi Aikawa, J.F. de Carvalho, C. Artur Almeida Silva, and E. Bonfá Immunogenicity of anti-TNF-alpha agents in autoimmune diseases Clin Rev Allergy Immunol 38 2010 82 89
40. A.A. Fasanmade, A. Olson, W. Bao, C. Pendley, H. Davis, and L. Mayer Relationship between infliximab pharmacokinetics and improvement in Crohn's disease Gastroenterology 122 (Suppl.) 2002 A617 A618
41. A.A. Fasanmade, O.J. Adedokun, M. Blank, H. Zhou, and H.M. Davis Pharmacokinetic properties of infliximab in children and ddults with Crohn's disease: a retrospective analysis of data from 2 Phase III clinical trials Clin Ther 33 2011 946 964
42. FDA Specific requirements on the content and format of labeling for human prescription drugs Revision of pediatric use subsection in the labeling: final Rule, 59 Federal Register 64240 1994
43. FDA Guidance for industry: general considerations for pediatric pharmacokinetic studies for drugs and biological products Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm072114.pdf 1998 Accessed July 6 2012
44. FDA Best Pharmaceuticals for Children Act Available at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ ucm049876.htm 2002 Accessed July 6 2012
45. FDA Pediatric Research Equity Act Available at http://www.fda.gov/ downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM077853.pdf 2003 Accessed July 6 2012
46. FDA Guidance for industry: exposure-response relationships - study design, data analysis and regulatory applications Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm072109.pdf 2003 Accessed July 6 2012
47. FDA Clinical pharmacology review for adalimumab (sBLA 125057/114, juvenile rheumatoid arthritis) Available at http://www.fda.gov/downloads/Drugs/ DevelopmentApprovalProcess/DevelopmentResources/UCM071556.pdf 2007 Accessed July 6 2012
48. FDA Clinical pharmacology review for omalizumab (sBLA 103976/5149) Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/ DevelopmentResources/UCM202181.pdf 2008 Accessed July 6 2012
49. FDA Information for healthcare professionals: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab) September 4, 2008. Available at http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm124185.htm 2008 Accessed July 6 2012
50. FDA Information for healthcare professionals: tumor necrosis factor (TNF) blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) August 4, 2009. Available at http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm174474.htm 2009 Accessed July 6 2012
51. FDA Clinical pharmacology review for tocilizumab (sBLA 125276/0022) Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/ DevelopmentResources/UCM259750.pdf 2011 Accessed July 6 2012
52. FDA UPDATE on tumor necrosis factor (TNF) blockers and risk for pediatric malignancy November 3, 2011. Available at http://www.fda.gov/Drugs/DrugSafety/ ucm278267.htm 2011 Accessed July 6, 2012
53. FDA Pediatric provisions in the Food and Drug Administration Safety and Innovation Act Available at http://www.fda.gov/RegulatoryInformation/ Legislation/FederalFoodDrugandCosmeticActFDCAct/ SignificantAmendmentstotheFDCAct/FDASIA/ucm311038.htm 2012 Accessed July 18, 2012
54. FDA Postmarket requirements and commitments Available at http://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm 2012 Accessed July 8 2012
55. FDA Advisory Committee for Pharmaceutical Science and Clinical Pharmacology: clinical pharmacology aspects of pediatric clinical trial design and dosing to optimize pediatric drug development Available at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm286681.htm 2012 Accessed July 6, 2012
56. E. Fox, and F.M. Balis Drug therapy in neonates and pediatric patients A.J. Atkinson, C.E. Daniels, R.L. Dedrick, C.V. Grudzinskas, S.P. Markey, Principles of clinical pharmacology 2001 Academic Press San Diego 293 305
57. G. Gartlehner, R.A. Hansen, B.L. Jonas, P. Thieda, and K.N. Lohr Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence Clin Rheumatol 27 2008 67 76
58. Genentech Inc Actemra® US prescribing information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/125276s0022s0023lbl. pdf 2011 Assessed July 6, 2012
59. J.T. Gilman, and P. Gal Pharmacokinetic and pharmacodynamic data collection in children and neonates. A quiet frontier Clin Pharmacokinet 23 1992 1 9
60. A.M. Griffiths Medical therapy for pediatric inflammatory bowel disease Curr Gastroenterol Rep 14 2012 166 173
61. S.B. Hanauer, and U. Stromberg Oral Pentasa in the treatment of active Crohn's disease: a meta-analysis of double-blind, placebo-controlled trials Clin Gastroenterol Hepatol 2 2004 379 388
62. S.B. Hanauer, B.G. Feagan, G.R. Lichtenstein, L.F. Mayer, S. Schreiber, and J.F. Colombel Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial Lancet 359 2002 1541 1549
63. T.T. Hansel, H. Kropshofer, T. Singer, J.A. Mitchell, and A.J. George The safety and side effects of monoclonal antibodies Nat Rev Drug Discov 9 2010 325 338
64. N. Hayashi, Y. Tsukamoto, W.M. Sallas, and P.J. Lowe A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab Br J Clin Pharmacol 63 2007 548 561
65. H.R. Hoogenboom Selecting and screening recombinant antibody libraries Nat Biotechnol 23 2005 1105 1116
66. C. Hu, Z. Xu, M.U. Rahman, H.M. Davis, and H. Zhou A latent variable approach for modeling categorical endpoints among patients with rheumatoid arthritis treated with golimumab plus methotrexate J Pharmacokinet Pharmacodyn 37 2010 309 321
67. J. Hyams, W. Crandall, S. Kugathasan, A. Griffiths, A. Olson, and J. Johanns Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children Gastroenterology 132 2007 863 873
68. J. Hyams, L. Damaraju, M. Blank, J. Johanns, C. Guzzo, and H.S. Winter Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis Clin Gastroenterol Hepatol 10 2012 391 399
69. ICH (International Conference on Harmonisation) Harmonised tripartite guideline: clinical investigation of medicinal products in the pediatric population E11 Available at http://www.ich.org/fileadmin/Public-Web-Site/ICH- Products/Guidelines/Efficacy/E11/Step4/E11-Guideline.pdf 2001 Accessed July 6, 2012
70. P.R. Jadhav, J. Zhang, and J.V. Gobburu Leveraging prior quantitative knowledge in guiding pediatric drug development: a case study Pharm Stat 8 2009 216 224
71. C. Jakobsen, J. Bartek Jr., V. Wewer, I. Vind, P. Munkholm, and R. Groen Differences in phenotype and disease course in adult and paediatric inflammatory bowel disease - a population-based study Aliment Pharmacol Ther 34 2011 1217 1224
72. S. Janmahasatian, S.B. Duffull, S. Ash, L.C. Ward, N.M. Byrne, and B. Green Quantification of lean bodyweight Clin Pharmacokinet 44 2005 1051 1065
73. Janssen Biotech Inc Remicade® US prescribing information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/103772s5295lbl.pdf 2011 Accessed July 6, 2012
74. Janssen Biotech Inc Simponi® US prescribing information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/125289s0064lbl.pdf 2011 Accessed July 6, 2012
75. T.N. Johnson Modelling approaches to dose estimation in children Br J Clin Pharmacol 59 2005 663 669
76. R.P. Junghans, and C.L. Anderson The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor Proc Natl Acad Sci U S A 93 1996 5512 5516
77. G.L. Kearns, S.M. Abdel-Rahman, S.W. Alander, D.L. Blowey, J.S. Leeder, and R.E. Kauffman Developmental pharmacology - drug disposition, action, and therapy in infants and children N Engl J Med 349 2003 1157 1167
78. R.J. Keizer, A.D. Huitema, J.H. Schellens, and J.H. Beijnen Clinical pharmacokinetics of therapeutic monoclonal antibodies Clin Pharmacokinet 49 2010 493 507
79. R. Keul, P.C. Heinrich, G. Müller-newen, K. Muller, and P. Woo A possible role for soluble IL-6 receptor in the pathogenesis of systemic onset juvenile chronic arthritis Cytokine 10 1998 729 734
80. E. Keystone, M.C. Genovese, L. Klareskog, E.C. Hsia, S. Hall, and P.C. Miranda Golimumab in patients with active rheumatoid arthritis despite methotrexate therapy: 52-week results of the GO-FORWARD study Ann Rheum Dis 69 2010 1129 1135
81. Y. Kimura, P. Pinho, G. Walco, G. Higgins, D. Hummell, and I. Szer Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis J Rheumatol 32 2005 935 942
82. G. Klement, P. Huang, B. Mayer, S.K. Green, S. Man, and P. Bohlen Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts Clin Cancer Res 8 2002 221 232
83. D.S. Kotlyar, M.T. Osterman, R.H. Diamond, D. Porter, W.C. Blonski, and M. Wasik A systematic review of factors that contribute to hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease Clin Gastroenterol Hepatol 9 2011 36 41
84. J. Kovarik, T. Breidenbach, C. Gerbeau, A. Korn, A.G. Schmidt, and B. Nashan Disposition and immunodynamics of basiliximab in liver allograft recipients Clin Pharmacol Ther 64 1998 66 72
85. J.M. Kovarik, G. Offner, M. Broyer, P. Niaudet, C. Loirat, and M. Mentser A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations Transplantation 74 2002 966 971
86. M. Lebwohl, N. Yeilding, P. Szapary, Y. Wang, S. Li, and Y. Zhu Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations J Am Acad Dermatol 63 2010 571 579
87. J.W. Lee, M. Kelley, L.E. King, J. Yang, H. Salimi-Moosavi, and M.T. Tang Bioanalytical approaches to quantify "total" and "free" therapeutic antibodies and their targets: technical challenges and PK/PD applications over the course of drug development AAPS J 13 2011 99 110
88. J.D. Lewis, J.S. Schwartz, and G.R. Lichtenstein Azathioprine for maintenance of remission in Crohn's disease: benefits outweigh the risk of lymphoma Gastroenterology 118 2000 1018 1024
89. G.R. Lichtenstein, S. Yan, M. Bala, and S. Hanauer Remission in patients with Crohn's disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries Am J Gastroenterol 99 2004 91 96
90. G.R. Lichtenstein, S. Yan, M. Bala, M. Blank, and B.E. Sands Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease Gastroenterology 128 2005 862 869
91. J.H. Lin Pharmacokinetic and pharmacodynamic variability: a daunting challenge in drug therapy Curr Drug Metab 8 2007 109 136
92. M.V. Lin, W. Blonski, and G.R. Lichtenstein What is the optimal therapy for Crohn's disease: step-up or top-down? Expert Rev Gastroenterol Hepatol 4 2010 167 180
93. P. Lionetti, F. Bronzini, C. Salvestrini, C. Bascietto, R.B. Canani, and G.L. Dé Angelis Response to infliximab is related to disease duration in paediatric Crohn's disease Aliment Pharmacol Ther 18 2003 425 431
94. E.D. Lobo, R.J. Hansen, and J.P. Balthasar Antibody pharmacokinetics and pharmacodynamics J Pharm Sci 93 2004 2645 2668
95. N. Lonberg Human antibodies from transgenic animals Nat Biotechnol 23 2005 1117 1125
96. D.J. Lovell, E.H. Giannini, A. Reiff, G.D. Cawkwell, E.D. Silverman, and J.J. Nocton Etanercept in children with polyarticular juvenile rheumatoid arthritis N Engl J Med 342 2000 763 769
97. D.J. Lovell, N. Ruperto, S. Goodman, A. Reiff, L. Jung, and K. Jarosova Adalimumab with or without methotrexate in juvenile rheumatoid arthritis N Engl J Med 359 2008 810 820
98. P.J. Lowe, S. Tannenbaum, A. Gautier, and P. Jimenez Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma Br J Clin Pharmacol 68 2009 61 76
99. I. Mahmood Prediction of drug clearance in children from adults: a comparison of several allometric methods Br J Clin Pharmacol 61 2006 545 557
100. I. Mahmood, and M.D. Green Pharmacokinetic and pharmacodynamic considerations in the development of therapeutic proteins Clin Pharmacokinet 44 2005 331 347
101. R. Maini, E.W. St Clair, F. Breedveld, D. Furst, J. Kalden, and M. Weisman Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group Lancet 354 1999 1932 1939
102. E. Manolis, and G. Pons Proposals for model-based paediatric medicinal development within the current European Union regulatory framework Br J Clin Pharmacol 68 2009 493 501
103. P.L. Martin, and P.J. Bugelski Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets Br J Pharmacol 166 2012 806 822
104. G. Martini, and F. Zulian Juvenile idiopathic arthritis: current and future treatment options Expert Opin Pharmacother 7 2006 387 399
105. N. Mehrotra, C. Garnett, L. Zhang, L. Fang, Y.M. Wang, and R.P. Fiorentino Role of exposure-response relationship to guide dose selection in pediatric drug development when extrapolating efficacy from adults Inflamm Bowel Dis 17 2011 S5
106. N. Mehrotra, Y. Wang, V.A. Bhattaram, J.C. Earp, J. Florian, and C. Garnett PK in late phase trials Available at http://www. appliedclinicaltrialsonline.com/ 2012 Accessed July 8, 2012
107. B. Meibohm, S. Läer, J.C. Panetta, and J.S. Barrett Population pharmacokinetic studies in pediatrics: issues in design and analysis AAPS J 7 2005 E475 E487
108. A. Meinhardt, B. Burkhardt, M. Zimmermann, A. Borkhardt, U. Kontny, and T. Klingebiel A Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia J Clin Oncol 28 2010 3115 3121
109. G.M. Meno-Tetang, and P.J. Lowe On the prediction of the human response: a recycled mechanistic pharmacokinetic/pharmacodynamic approach Basic Clin Pharmacol Toxicol 96 2005 182 192
110. R. Modigliani, J.Y. Mary, J.F. Simon, A. Cortot, J.C. Soule, and J.P. Gendre Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone Gastroenterology 98 1990 811 818
111. D.R. Mould, and B. Green Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and lessons for drug development BioDrugs 24 2010 23 39
112. T.M. Olski, S.F. Lampus, G. Gherarducci, and A. Saint Raymond Three years of paediatric regulation in the European Union Eur J Clin Pharmacol 67 2011 245 252
113. V. Pascual, F. Allantaz, E. Arce, M. Punaro, and J. Banchereau Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade J Exp Med 201 2005 1479 1486
114. B. Pigneur, P. Seksik, S. Viola, J. Viala, L. Beaugerie, and J.P. Girardet Natural history of Crohn's disease: comparison between childhood- and adult-onset disease Inflamm Bowel Dis 16 2010 953 961
115. C.J. Porter, and S.A. Charman Lymphatic transport of proteins after subcutaneous administration J Pharm Sci 89 2000 297 310
116. E. Prefontaine, L.R. Sutherland, J.K. Macdonald, and M. Cepoiu Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn's disease Cochrane Database Syst Rev 1 2009 CD000067
117. D.H. Present, B.I. Korelitz, N. Wisch, J.L. Glass, D.B. Sachar, and B.S. Pasternack Treatment of Crohn's disease with 6-mercaptopurine: a long-term, randomized, double-blind study N Engl J Med 302 1980 981 987
118. D.H. Present, P. Rutgeerts, S. Targan, S.B. Hanauer, L. Mayer, and R.A. van Hogezand Infliximab for the treatment of fistulas in patients with Crohn's disease N Engl J Med 340 1999 1398 1405
119. T. Puchalski, U. Prabhakar, Q. Jiao, B. Berns, and H.M. Davis Pharmacokinetic and pharmacodynamic modeling of an anti-interleukin-6 chimeric monoclonal antibody (siltuximab) in patients with metastatic renal cell carcinoma Clin Cancer Res 16 2010 1652 1661
120. M.U. Rahman, I. Strusberg, P. Geusens, A. Berman, D. Yocum, and D. Baker Double-blinded infliximab dose escalation in patients with rheumatoid arthritis Ann Rheum Dis 66 2007 1233 1238
121. A. Ravelli, and A. Martini Juvenile idiopathic arthritis Lancet 369 2007 767 778
122. M. Regueiro, B. Siemanowski, K.E. Kip, and S. Plevy Infliximab dose intensification in Crohn's disease Inflamm Bowel Dis 13 2007 1093 1099
123. M. Regueiro, W. Schraut, L. Baidoo, K.E. Kip, A.R. Sepulveda, and M. Pesci Infliximab prevents Crohn's disease recurrence after ileal resection Gastroenterology 136 2009 441 450
124. J.M. Reichert Marketed therapeutic antibodies compendium MAbs 4 2012 413 415
125. G.J. Robbie, L. Zhao, J. Mondick, G. Losonsky, and L.K. Roskos Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children Antimicrob Agents Chemother 56 2012 4927 4936
126. R. Roberts, W. Rodriguez, D. Murphy, and T. Crescenzi Pediatric drug labeling: improving the safety and efficacy of pediatric therapies JAMA 290 2003 905 911
127. W. Rodriguez, A. Selen, D. Avant, C. Chaurasia, T. Crescenzi, and G. Gieser Improving pediatric dosing through pediatric initiatives: what we have learned Pediatrics 121 2008 530 539
128. H. Rosenblum, and H. Amital Anti-TNF therapy: safety aspects of taking the risk Autoimmun Rev 10 2011 563 568
129. N. Ruperto, D.J. Lovell, R. Cuttica, N. Wilkinson, P. Woo, and G. Espada A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis Arthritis Rheum 56 2007 3096 3106
130. N. Ruperto, D.J. Lovell, P. Quartier, E. Paz, N. Rubio-Pérez, and C.A. Silva Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial Lancet 372 2008 383 391
131. N. Ruperto, P. Quartier, N. Wulffraat, P. Woo, A. Ravelli, and R. Mouy A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features Arthritis Rheum 64 2012 557 567
132. P. Rutgeerts, W.J. Sandborn, B.G. Feagan, W. Reinisch, A. Olson, and J. Johanns Infliximab for induction and maintenance therapy for ulcerative colitis N Engl J Med 353 2005 2462 2476
133. P. Rutgeerts, R.H. Diamond, M. Bala, A. Olson, G.R. Lichtenstein, and W. Bao Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease Gastrointest Endosc 63 2006 433 442
134. C. Salliot, A. Finckh, W. Katchamart, Y. Lu, Y. Sun, and C. Bombardier Indirect comparisons of the efficacy of biological antirheumatic agents in rheumatoid arthritis in patients with an inadequate response to conventional disease-modifying antirheumatic drugs or to an anti-tumour necrosis factor agent: a meta-analysis Ann Rheum Dis 70 2011 266 271
135. H. Sammons Ethical issues of clinical trials in children: a European perspective Arch Dis Child 94 2009 474 477
136. W.J. Sandborn, B.G. Feagan, S. Stoinov, P.J. Honiball, P. Rutgeerts, and D. Mason Certolizumab pegol for the treatment of Crohn's disease N Engl J Med 357 2007 228 238
137. B.E. Sands, F.H. Anderson, C.N. Bernstein, W.Y. Chey, B.G. Feagan, and R.N. Fedorak Infliximab maintenance therapy for fistulizing Crohn's disease N Engl J Med 350 2004 876 885
138. H. Schellekens The immunogenicity of therapeutic proteins Discov Med 9 2010 560 564
139. C.H. Seow, A. Newman, S.P. Irwin, A.H. Steinhart, M.S. Silverberg, and G.R. Greenberg Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis Gut 59 2010 49 54
140. R.E. Shaddy, and S.C. Denne Clinical report - guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations Pediatrics 125 2010 850 860
141. M.E. Sherlock, A.M. Buchner, W. Blonski, and G.R. Lichtenstein Update on the management of Crohn's disease Curr Gastroenterol Rep 13 2011 465 474
142. K.E. Smedby, J. Askling, X. Mariette, and E. Baecklund Autoimmune and inflammatory disorders and risk of malignant lymphomas - an update J Intern Med 264 2008 514 527
143. S.L. Smith Ten years of orthoclone OKT3 (muromonab-CD3): a review J Transpl Coord 6 1996 109 119
144. P.B. Smith, D.K. Benjamin Jr., M.D. Murphy, R. Johann-Liang, S. Iyasu, and B. Gould Safety monitoring of drugs receiving pediatric marketing exclusivity Pediatrics 122 2008 e628 e633
145. E.W. St Clair, C.L. Wagner, A.A. Fasanmade, B. Wang, T. Schaible, and A. Kavanaugh The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial Arthritis Rheum 46 2002 1451 1459
146. T. Stephenson How children's responses to drugs differ from adults Br J Clin Pharmacol 59 2005 670 673
147. R. Stern, and F. Wolfe Infliximab dose and clinical status: results of 2 studies in 1642 patients with rheumatoid arthritis J Rheumatol 31 2004 1538 1545
148. H. Sun, E.O. Fadiran, C.D. Jones, L. Lesko, S.M. Huang, and K. Higgins Population pharmacokinetics. A regulatory perspective Clin Pharmacokinet 37 1999 41 58
149. L. Sutjandra, R.D. Rodriguez, S. Doshi, M. Ma, M.C. Peterson, and G.R. Jang Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis Clin Pharmacokinet 50 2011 793 807
150. M.A. Tabrizi, and L.K. Roskos Preclinical and clinical safety of monoclonal antibodies Drug Discov Today 12 2007 540 547
151. M.A. Tabrizi, C.M. Tseng, and L.K. Roskos Elimination mechanisms of therapeutic monoclonal antibodies Drug Discov Today 11 2006 81 88
152. M. Tabrizi, G.G. Bornstein, and H. Suria Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease AAPS J 12 2010 33 43
153. S.R. Targan, S.B. Hanauer, S.J. van Deventer, L. Mayer, D.H. Present, and T. Braakman 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 337 1997 1029 1035
154. M. Tod, F. Mentré, Y. Merlé, and A. Mallet Robust optimal design for the estimation of hyperparameters in population pharmacokinetics J Pharmacokinet Biopharm 26 1998 689 716
155. G. Toedter, K. Hayden, C. Wagner, and C. Brodmerkel Simultaneous detection of eight analytes in human serum by two commercially available platforms for multiplex cytokine analysis Clin Vaccine Immunol 15 2008 42 48
156. D. Tracey, L. Klareskog, E.H. Sasso, J.G. Salfeld, and P.P. Tak Tumor necrosis factor antagonist mechanisms of action: a comprehensive review Pharmacol Ther 117 2008 244 279
157. T.M. Trippett, C. Herzog, J.A. Whitlock, J. Wolff, J. Kuttesch, and R. Bagatell Phase I and pharmacokinetic study of cetuximab and irinotecan in children with refractory solid tumors: a study of the pediatric oncology experimental therapeutic investigators' consortium J Clin Oncol 27 2009 5102 5108
158. UCB Inc Cimzia® US prescribing information Available at http://www.accessdata.fda.gov/drugsatfda-docs/label/2012/125160s0174lbl.pdf 2012 Accessed July 6, 2012
159. J.M. Van den Brande, H. Braat, G.R. van den Brink, H.H. Versteeg, C.A. Bauer, and I. Hoedemaeker Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease Gastroenterology 124 2003 1774 1785
160. S. Vermeire, G. van Assche, and P. Rutgeerts Altering the natural history of Crohn's disease - evidence for and against current therapies Aliment Pharmacol Ther 25 2007 3 12
161. J. Wang, and L. Endrenyi A computationally efficient approach for the design of population pharmacokinetic studies J Pharmacokinet Biopharm 20 1992 279 294
162. D.D. Wang, S. Zhang, H. Zhao, A.Y. Men, and K. Parivar Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials J Clin Pharmacol 49 2009 1012 1024
163. L.M. Weiner, and H. Borghaei Targeted therapies in solid tumors: monoclonal antibodies and small molecules Hum Antibodies 15 2006 103 111
164. G.B. West, J.H. Brown, and B.J. Enquist A general model for the origin of allometric scaling laws in biology Science 276 1997 122 126
165. G.J. Wolbink, L.A. Aarden, and B.A. Dijkmans Dealing with immunogenicity of biologicals: assessment and clinical relevance Curr Opin Rheumatol 21 2009 211 215
166. R.J. Xavier, and D.K. Podolsky Unravelling the pathogenesis of inflammatory bowel disease Nature 448 2007 427 434
167. Z. Xu, K. Seitz, A. Fasanmade, J. Ford, P. Williamson, and W. Xu Population pharmacokinetics of infliximab in patients with ankylosing spondylitis J Clin Pharmacol 48 2008 681 695
168. Z. Xu, T. Vu, H. Lee, C. Hu, J. Ling, and H. Yan Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human
169. Z.H. Xu, H. Lee, T. Vu, C. Hu, H. Yan, and D. Baker Population pharmacokinetics of golimumab in patients with ankylosing spondylitis: impact of body weight and immunogenicity Int J Clin Pharmacol Ther 48 2010 596 607
170. Z. Xu, Q. Wang, Y. Zhuang, B. Frederick, H. Yan, and E. Bouman-Thio Subcutaneous bioavailability of golimumab at 3 different injection sites in healthy subjects J Clin Pharmacol 50 2010 276 284
171. Z. Xu, D.R. Mould, C. Hu, J. Ford, M. Keen, and H.M. Davis Population pharmacokinetic analysis of infliximab in pediatrics using integrated data from six clinical trials Clin Pharmacol Drug Dev 1 2012 203
172. D.S. Yim, H. Zhou, M. Buckwalter, I. Nestorov, C.C. Peck, and H. Lee Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis J Clin Pharmacol 45 2005 246 256
173. S. Yokota, T. Miyamae, T. Imagawa, N. Iwata, S. Katakura, and M. Mori Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis Arthritis Rheum 2005 52 2005 818 825
174. S. Yokota, T. Imagawa, M. Mori, T. Miyamae, Y. Aihara, and S. Takei Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial Lancet 371 2008 998 1006
175. H. Zhou, and M.A. Mascelli Mechanisms of monoclonal antibody-drug interactions Annu Rev Pharmacol Toxicol 51 2011 359 372
176. H. Zhou, C. Hu, Y. Zhu, M. Lu, S. Liao, and N. Yeilding Population-based exposure-efficacy modeling of ustekinumab in patients with moderate to severe plaque psoriasis J Clin Pharmacol 50 2010 257 267
177. Y. Zhuang, Z. Xu, B. Frederick, D.E. de Vries, J.A. Ford, and M. Keen Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study Clin Ther 34 2012 77 90