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Review

Impact of Shed/Soluble targets on the PK/PD of approved therapeutic monoclonal antibodies

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Pages 1557-1569 | Received 15 Apr 2016, Accepted 27 Sep 2016, Published online: 21 Oct 2016

References

  • Lu D, Girish S, Gao Y, et al. Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates. Cancer Chemother Pharmacol. 2014;74(2):399–410.
  • Davda JP, Dodds MG, Gibbs MA, et al. A model-based meta-analysis of monoclonal antibody pharmacokinetics to guide optimal first-in-human study design. mAbs. 2014;6(4):1094–1102.
  • Peng K, Baker D, Brignoli S, et al. When assay format matters: a case study on the evaluation of three assay formats to support a clinical pharmacokinetic study. AAPS J. 2014;16(4):625–633.
  • Tabrizi M, Bornstein GG, Suria H. Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J. 2010;12(1):33–43.
  • Wang W, Wang X, Doddareddy R, et al. Mechanistic pharmacokinetic/target engagement/pharmacodynamic modeling in deciphering interplay between a monoclonal antibody and its soluble target in cynomolgus monkeys. AAPS J. 2014;16(1):129–139.
  • Zheng S, McIntosh T, Wang W. Utility of free and total target measurements as target engagement and efficacy biomarkers in biotherapeutic development–opportunities and challenges. J Clin Pharmacol. 2015;55(Suppl 3):S75–S84.
  • Lee JW, Kelley M, King LE, et al. 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. 2011;13(1):99–110.
  • Ardestani S, Li B, Deskins DL, et al. Membrane versus soluble isoforms of TNF-alpha exert opposing effects on tumor growth and survival of tumor-associated myeloid cells. Cancer Res. 2013;73(13):3938–3950.
  • Luetteke NC, Lee DC. Transforming growth factor alpha: expression, regulation and biological action of its integral membrane precursor. Semin Cancer Biol. 1990;1(4):265–275.
  • Giles FJ, Vose JM, Do KA, et al. Circulating CD20 and CD52 in patients with non-Hodgkin’s lymphoma or Hodgkin’s disease. Br J Haematol. 2003;123(5):850–857.
  • Lennon S, Barton C, Banken L, et al. Utility of serum HER2 extracellular domain assessment in clinical decision making: pooled analysis of four trials of trastuzumab in metastatic breast cancer. J Clin Oncology. 2009;27(10):1685–1693.
  • Ternant D, Ducourau E, Fuzibet P, et al. Pharmacokinetics and concentration-effect relationship of adalimumab in rheumatoid arthritis. Br J Clin Pharmacol. 2015;79(2):286–297.
  • Lu JF, Bruno R, Eppler S, et al. Clinical pharmacokinetics of bevacizumab in patients with solid tumors. Cancer Chemother Pharmacol. 2008;62(5):779–786.
  • Struemper H, Chen C, Cai W. Population pharmacokinetics of belimumab following intravenous administration in patients with systemic lupus erythematosus. J Clin Pharmacol. 2013;53(7):711–720.
  • Wade JR, Parker G, Kosutic G, et al. Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn’s disease. J Clin Pharmacol. 2015;55(8):866–874.
  • Lachmann HJ, Lowe P, Felix SD, et al. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med. 2009;206(5):1029–1036.
  • Xu L, Lu T, Tuomi L, et al. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: a population approach. Invest Ophthalmol Vis Sci. 2013;54(3):1616–1624.
  • Furuya Y, Ozeki T, Takayanagi R, et al. Theory based analysis of anti-inflammatory effect of infliximab on Crohn’s disease. Drug Metab Pharmacokinet. 2007;22(1):20–25.
  • Xu Z, Vu T, Lee H, et al. Population pharmacokinetics of golimumab, an anti-tumor necrosis factor-alpha human monoclonal antibody, in patients with psoriatic arthritis. J Clin Pharmacol. 2009;49(9):1056–1070.
  • Zhu Y, Hu C, Lu M, et al. Population pharmacokinetic modeling of ustekinumab, a human monoclonal antibody targeting IL-12/23p40, in patients with moderate to severe plaque psoriasis. J Clin Pharmacol. 2009;49(2):162–175.
  • Sutjandra L, Rodriguez RD, Doshi S, et al. Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. Clin Pharmacokinet. 2011;50(12):793–807.
  • Hayashi N, Tsukamoto Y, Sallas WM, et al. A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab. Br J Clin Pharmacol. 2007;63(5):548–561.
  • Frey N, Grange S, Woodworth T. Population pharmacokinetic analysis of tocilizumab in patients with rheumatoid arthritis. J Clin Pharmacol. 2010;50(7):754–766.
  • Struemper H, Sale M, Patel BR, et al. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014;54(7):818–827.
  • Mould DR, Baumann A, Kuhlmann J, et al. Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukaemia and its link to treatment response. Br J Clin Pharmacol. 2007;64(3):278–291.
  • Tan AR, Moore DF, Hidalgo M, et al. Pharmacokinetics of cetuximab after administration of escalating single dosing and weekly fixed dosing in patients with solid tumors. Clin Cancer Research. 2006;12(21):6517–6522.
  • Gibiansky E, Gibiansky L, Carlile DJ, et al. Population pharmacokinetics of obinutuzumab (GA101) in chronic lymphocytic leukemia (CLL) and Non-Hodgkin’s lymphoma and exposure-response in CLL. CPT Pharmacometrics Syst Pharmacol. 2014;3:e144.
  • Cosson VF, Ng VW, Lehle M, et al. Population pharmacokinetics and exposure-response analyses of trastuzumab in patients with advanced gastric or gastroesophageal junction cancer. Cancer Chemother Pharmacol. 2014;73(4):737–747.
  • McLaughlin P, Grillo-Lopez AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncology. 1998;16(8):2825–2833.
  • Li J, Zhi J, Wenger M, et al. Population pharmacokinetics of rituximab in patients with chronic lymphocytic leukemia. J Clin Pharmacol. 2012;52(12):1918–1926.
  • Ng CM, Bruno R, Combs D, et al. Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in rheumatoid arthritis patients during a phase II clinical trial. J Clin Pharmacol. 2005;45(7):792–801.
  • Ma P, Yang BB, Wang YM, et al. Population pharmacokinetic analysis of panitumumab in patients with advanced solid tumors. J Clin Pharmacol. 2009;49(10):1142–1156.
  • Feng Y, Masson E, Dai D, et al. Model-based clinical pharmacology profiling of ipilimumab in patients with advanced melanoma. Br J Clin Pharmacol. 2014;78(1):106–117.
  • Kuang B, King L, Wang HF. Therapeutic monoclonal antibody concentration monitoring: free or total? Bioanalysis. 2010;2(6):1125–1140.
  • Kimko HC, Peck CC. American association of pharmaceutical scientists. In: Clinical trial simulations: applications and trends. New York: AAPS Press; 2011.
  • Lee JW, Salimi-Moosavi H. Bioanalysis of target biomarker and PK/PD relevancy during the development of biotherapeutics. Bioanalysis. 2012;4(20):2513–2523.
  • Roskos LK, Schneider A, Vainshtein I, et al. PK-PD modeling of protein drugs: implications in assay development. Bioanalysis. 2011;3(6):659–675.
  • Fischer SK, Yang J, Anand B, et al. The assay design used for measurement of therapeutic antibody concentrations can affect pharmacokinetic parameters: case studies. mAbs. 2012;4(5):623–631.
  • Shah JJ, Feng L, Thomas SK, et al. Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial. Blood Cancer J. 2016;6:e396.
  • Dowell JA, Korth-Bradley J, Liu H, et al. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J Clin Pharmacol. 2001;41(11):1206–1214.
  • Joshi A, Bauer R, Kuebler P, et al. An overview of the pharmacokinetics and pharmacodynamics of efalizumab: a monoclonal antibody approved for use in psoriasis. J Clin Pharmacol. 2006;46(1):10–20.
  • Beer PM, Wong SJ, Hammad AM, et al. Vitreous levels of unbound bevacizumab and unbound vascular endothelial growth factor in two patients. Retina. 2006;26(8):871–876.
  • Slavin RG, Ferioli C, Tannenbaum SJ, et al. Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations. J Allergy Clin Immunol. 2009;123(1):107–113 e103.
  • Hamilton RG, Marcotte GV, Saini SS. Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy. J Immunol Methods. 2005;303(1–2):81–91.
  • Ternant D, Mulleman D, Degenne D, et al. An enzyme-linked immunosorbent assay for therapeutic drug monitoring of infliximab. Ther Drug Monit. 2006;28(2):169–174.
  • Charles P, Elliott MJ, Davis D, et al. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis. J Immunol. 1999;163(3):1521–1528.
  • Manshouri T, Do KA, Wang X, et al. Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood. 2003;101(7):2507–2513.
  • Cartron G, Blasco H, Paintaud G, et al. Pharmacokinetics of rituximab and its clinical use: thought for the best use? Crit Rev Oncol Hematol. 2007;62(1):43–52.
  • Beum PV, Kennedy AD, Taylor RP. Three new assays for rituximab based on its immunological activity or antigenic properties: analyses of sera and plasmas of RTX-treated patients with chronic lymphocytic leukemia and other B cell lymphomas. J Immunol Methods. 2004;289(1–2):97–109.
  • Barrera P, Joosten LA, den Broeder AA, et al. Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Ann Rheum Dis. 2001;60(7):660–669.
  • Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncology. 2001;19(3):843–850.
  • Gijbels K, Brocke S, Abrams JS, et al. Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol Med. 1995;1(7):795–805.
  • Chakraborty A, Tannenbaum S, Rordorf C, et al. Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1beta monoclonal antibody. Clin Pharmacokinet. 2012;51(6):e1–18.
  • Hansen RJ, Brown RM, Lu J, et al. Qualification of a free ligand assay in the presence of anti-ligand antibody Fab fragments. mAbs. 2013;5(2):288–296.
  • Davda JP, Hansen RJ. Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets. mAbs. 2010;2(5):576–588.
  • Weisman MH, Moreland LW, Furst DE, et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther. 2003;25(6):1700–1721.
  • Sartelli M, Malangoni MA, Abu-Zidan FM, et al. WSES guidelines for management of Clostridium difficile infection in surgical patients. World J Emerg Surgery. 2015;10:38.
  • Kut C, Mac Gabhann F, Popel AS. Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer. Br J Cancer. 2007;97(7):978–985.
  • Mould DR, Sweeney KR. The pharmacokinetics and pharmacodynamics of monoclonal antibodies–mechanistic modeling applied to drug development. Curr Opin Drug Discov Devel. 2007;10(1):84–96.
  • Luo Y, Lu Z, Raso SW, et al. Dimers and multimers of monoclonal IgG1 exhibit higher in vitro binding affinities to Fcgamma receptors. mAbs. 2009;1(5):491–504.
  • Christianson GJ, Sun VZ, Akilesh S, et al. Monoclonal antibodies directed against human FcRn and their applications. mAbs. 2012;4(2):208–216.
  • Ratcliffe A, Stanworth DR. Measurement of the binding activity of defined IgG aggregates to macrophage Fc receptors. Immunol Lett. 1983;7(2):73–76.
  • Segal DM, Hurwitz E. Binding of affinity cross-linked oligomers of IgG to cells bearing Fc receptors. J Immunol. 1977;118(4):1338–1337.
  • Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19(7):1059–1066.
  • Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Research. 2006;12(4):1221–1228.
  • McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821–831.
  • Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–176.
  • Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci U S A. 2000;97(4):1566–1571.
  • Nakagawa N, Kinosaki M, Yamaguchi K, et al. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 1998;253(2):395–400.
  • Arthur KK, Gabrielson JP, Hawkins N, et al. In vitro stoichiometry of complexes between the soluble RANK ligand and the monoclonal antibody denosumab. Biochemistry. 2012;51(3):795–806.
  • Gibiansky L, Sutjandra L, Doshi S, et al. Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Clin Pharmacokinet. 2012;51(4):247–260.
  • Evans C, Arnold M, Bryan P, et al. Implementing dried blood spot sampling for clinical pharmacokinetic determinations: considerations from the IQ consortium microsampling working group. AAPS J. 2015;17(2):292–300.
  • Fasanmade AA, Adedokun OJ, Ford J, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009;65(12):1211–1228.
  • Dotan I, Ron Y, Yanai H, et al. Patient factors that increase infliximab clearance and shorten half-life in inflammatory bowel disease: a population pharmacokinetic study. Inflamm Bowel Dis. 2014;20(12):2247–2259.
  • Vena GA, Cassano N. Drug focus: adalimumab in the treatment of moderate to severe psoriasis. Biologics. 2007;1(2):93–103.
  • Kohno T, Tam LT, Stevens SR, et al. Binding characteristics of tumor necrosis factor receptor-Fc fusion proteins vs anti-tumor necrosis factor mAbs. J Investig Dermatol Symp Proc. 2007;12(1):5–8.
  • Kim MS, Lee SH, Song MY, et al. Comparative analyses of complex formation and binding sites between human tumor necrosis factor-alpha and its three antagonists elucidate their different neutralizing mechanisms. J Mol Biol. 2007;374(5):1374–1388.
  • High K, Meng Y, Washabaugh MW, et al. Determination of picomolar equilibrium dissociation constants in solution by enzyme-linked immunosorbent assay with fluorescence detection. Anal Biochem. 2005;347(1):159–161.
  • Khanna R, Feagan BG. Current and future status of therapeutic drug monitoring in the treatment of IBD. Curr Treat Options Gastroenterol. 2014;12(1):76–89.
  • Baker MP, Reynolds HM, Lumicisi B, et al. Immunogenicity of protein therapeutics: the key causes, consequences and challenges. Self Nonself. 2010;1(4):314–322.
  • McCain ME, Quinet RJ, Davis WE. Etanercept and infliximab associated with cutaneous vasculitis. Rheumatology (Oxford). 2002;41(1):116–117.
  • Bruno R, Washington CB, Lu JF, et al. Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic breast cancer. Cancer Chemother Pharmacol. 2005;56(4):361–369.
  • Lowe PJ, Georgiou P, Canvin J. Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE. Regul Toxicol Pharmacology. 2015;71(1):68–77.
  • Li L, Gardner I, Rose R, et al. Incorporating target shedding into a minimal PBPK-TMDD model for monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol. 2014;3:e96.
  • Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncology. 1996;14(3):737–744.
  • Fayer BE, Soni PP, Binger MH, et al. Determination of humanized anti-Tac in human serum by a sandwich enzyme linked immunosorbent assay. J Immunol Methods. 1995;186(1):47–54.
  • van der Velden VH, Boeckx N, Jedema I, et al. High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg) treatment in acute myeloid leukemia patients. Leukemia. 2004;18(5):983–988.
  • Albitar M, Do KA, Johnson MM, et al. Free circulating soluble CD52 as a tumor marker in chronic lymphocytic leukemia and its implication in therapy with anti-CD52 antibodies. Cancer. 2004;101(5):999–1008.
  • Molina R, Jo J, Filella X, et al. C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients. Anticancer Res. 1999;19(4A):2551–2555.
  • Baselga J, Tripathy D, Mendelsohn J, et al. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. Semin Oncol. 1999;26(4 Suppl 12):78–83.
  • Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncology. 2002;20(3):719–726.
  • Even-Desrumeaux K, Baty D, Chames P. State of the art in tumor antigen and biomarker discovery. Cancers. 2011;3(2):2554–2596.
  • Meno-Tetang GM, Lowe PJ. On the prediction of the human response: a recycled mechanistic pharmacokinetic/pharmacodynamic approach. Basic Clin Pharmacol Toxicol. 2005;96(3):182–192.
  • Deprimo SE, Bello CL, Smeraglia J, et al. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J Transl Med. 2007;5:32.
  • Allerheiligen SR. Next-generation model-based drug discovery and development: quantitative and systems pharmacology. Clin Pharmacol Ther. 2010;88(1):135–137.
  • Lowe PJ, Tannenbaum S, Gautier A, et al. Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma. Br J Clin Pharmacol. 2009;68(1):61–76.
  • Adelroth E, Rak S, Haahtela T, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2000;106(2):253–259.
  • Mager DE, Jusko WJ. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J Pharmacokinet Pharmacodyn. 2001;28(6):507–532.
  • Kirkham BW, Lassere MN, Edmonds JP, et al. Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum. 2006;54(4):1122–1131.
  • Kievit W, Fransen J, Oerlemans AJ, et al. The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice. Ann Rheum Dis. 2007;66(11):1473–1478.
  • Marathe A, Peterson MC, Mager DE. Integrated cellular bone homeostasis model for denosumab pharmacodynamics in multiple myeloma patients. J Pharmacol Exp Ther. 2008;326(2):555–562.
  • Lemaire V, Tobin FL, Greller LD, et al. Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J Theor Biol. 2004;229(3):293–309.
  • Zalevsky J, Chamberlain AK, Horton HM, et al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 2010;28(2):157–159.
  • Igawa T, Mimoto F, Hattori K. pH-dependent antigen-binding antibodies as a novel therapeutic modality. Biochim Biophys Acta. 2014;1844(11):1943–1950.

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