Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-Targeted Dual-Variable Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid Arthritis: Results from Three Phase I Trials

Clinical Pharmacokinetics

Volumn 57, Issue 5, 2018, Pages 613-623

  Khatri, Amit ^a   Goss, Sandra ^a   Jiang, Ping ^a   Mansikka, Heikki ^a   Othman, Ahmed A ^a  

^a ABBVIE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG ANTIBODY; IMMUNOGLOBULIN; INTERLEUKIN 17; METHOTREXATE; REMTOLUMAB; TUMOR NECROSIS FACTOR; ABT-122; ANTIRHEUMATIC AGENT; IL17A PROTEIN, HUMAN;

ADULT; AGED; ANTIBODY TITER; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISPOSITION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ERYTHEMA; FEMALE; HEADACHE; HUMAN; INJECTION SITE REACTION; MAJOR CLINICAL STUDY; MALE; PHASE 1 CLINICAL TRIAL (TOPIC); PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RHEUMATOID ARTHRITIS; STEADY STATE; TREATMENT OUTCOME; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BLOOD; CLINICAL TRIAL; DOUBLE BLIND PROCEDURE; METABOLISM; MIDDLE AGED; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; DOUBLE-BLIND METHOD; FEMALE; HEALTHY VOLUNTEERS; HUMANS; IMMUNOGLOBULINS; INTERLEUKIN-17; MALE; MIDDLE AGED; TUMOR NECROSIS FACTOR-ALPHA; YOUNG ADULT;

EID: 85025813469     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-017-0580-y     Document Type: Article

References (28)

1. Arthritis Foundation. http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php. Accessed 11 July 2017.
2. Centers for Disease Control and Prevention. Rheumatoid arthritis (RA). http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed 11 July 2017.
3. European Federation of Pharmaceutical Industries and Associations. Rheumatoid arthritis. http://www.efpia.eu/diseases/112/59/Rheumatoid-Arthritis. Accessed 11 July 2017.
4. Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509. doi:10.1136/annrheumdis-2013-204573.
5. Nirula A, Nilsen J, Klekotka P, Kricorian G, Erondu N, Towne JE, et al. Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases. Rheumatology (Oxford). 2016;55(Suppl. 2):ii43–55. doi:10.1093/rheumatology/kew346.
6. Kunwar S, Dahal K, Sharma S. Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatol Int. 2016;36(8):1065–75. doi:10.1007/s00296-016-3480-9.
7. Nam JL, Ramiro S, Gaujoux-Viala C, Takase K, Leon-Garcia M, Emery P, et al. Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):516–28. doi:10.1136/annrheumdis-2013-204577.
8. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–76. doi:10.1038/nrd3794.
9. Koenders MI, Marijnissen RJ, Devesa I, Lubberts E, Joosten LA, Roth J, et al. Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1beta, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum. 2011;63(8):2329–39. doi:10.1002/art.30418.
10. van Hamburg JP, Asmawidjaja PS, Davelaar N, Mus AM, Colin EM, Hazes JM, et al. Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 2011;63(1):73–83. doi:10.1002/art.30093.
11. Kirkham BW, Lassere MN, Edmonds JP, Juhasz KM, Bird PA, Lee CS, 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):1122–31. doi:10.1002/art.21749.
12. Hsieh C-M, Cuff C, Tarcsa E, Hugunin M. FRI0303 Discovery and characterization of ABT-122, an anti-TNF/IL-17 DVD-Ig™ molecule as a potential therapeutic candidate for rheumatoid arthritis. Ann Rheum Dis. 2014;73(Suppl. 2):495. doi:10.1136/annrheumdis-2014-eular.4676.
13. Fleischmann R, Wagner F, Kivitz AJ, Mansikka H, Khan N, Othman AA, et al. Safety, tolerability, and pharmacodynamics of ABT-122, a TNF- and IL-17-targeted dual variable domain immunoglobulin, in patients with RA. Arthritis Rheum. 2017 (submitted).
14. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244–79. doi:10.1016/j.pharmthera.2007.10.001.
15. Beringer A, Noack M, Miossec P. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med. 2016;22(3):230–41. doi:10.1016/j.molmed.2016.01.001.
16. Mansikka H, Ruzek M, Hugunin M, Ivanov A, Brito A, Clabbers A, et al. Safety, tolerability, and functional activity of ABT-122, a dual TNF- and IL-17A–targeted DVD-Ig™, following single-dose administration in healthy subjects. Ann Rheum Dis. 2015;74(Suppl. 2):482–3.
17. Cuff C, Ruzek M, Padley R, Mansikka H, Voss J, Hugunin M, et al. Mechanisms of dual inhibition of TNF and IL-17: translation to clinical studies with ABT-122. Inflamm Res. 2015;64(2):S98–9. doi:10.1007/s00787-015-0714-4.
18. Cuff C, Bryant S, Hugunin M, Kamath R, Voss J, Olson L, et al. Dual neutralization of TNF and IL-17 with a DVD-Ig protein is efficacious in collagen induced arthritis. Ann Rheum Dis. 2014;73:363. doi:10.1136/annrheumdis-2014-eular.5383.
19. van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63(5):508–16. doi:10.1136/ard.2003.013052.
20. AbbVie. Adalimumab (US prescribing information). North Chicago: AbbVie; 2017.
21. Janssen Biotech, Inc. Infliximab (US prescribing information). Horsham: Janssen Biotech, Inc.; 2015.
22. Novartis. Secukinumab (US prescribing information). East Hanover: Novartis; 2016.
23. Eli Lilly and Company. Ixekizumab (US prescribing information). Indianapolis: Eli Lilly and Company; 2016.
24. Kamath AV. Translational pharmacokinetics and pharmacodynamics of monoclonal antibodies. Drug Discov Today Technol. 2016;21–22:75–83. doi:10.1016/j.ddtec.2016.09.004.
25. Janssen Biotech, Inc. Golimumab (US prescribing information). Horsham: Janssen Biotech, Inc.; 2017.
26. Immunex Corporation. Etanercept (US prescribing information). Thousand Oaks: Immunex Corporation; 2009.
27. Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28(4):454–67. doi:10.1016/j.immuni.2008.03.004.
28. Khader SA, Gopal R. IL-17 in protective immunity to intracellular pathogens. Virulence. 2010;1(5):423–7. doi:10.4161/viru.1.5.12862.