Exposure-response relationship of tocilizumab, an anti - IL-6 receptor monoclonal antibody, in a large population of patients with rheumatoid arthritis

Journal of Clinical Pharmacology

Volumn 53, Issue 2, 2013, Pages 151-159

  Levi, Micha ^a   Grange, Susan ^b   Frey, Nicolas ^b  

^a HOFFMANN LA ROCHE INC   (United States)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Clinical pharmacology; Clinical trials; Immunopharmacology; Pharmacodynamics; Rheumatology immunology

Indexed keywords

DISEASE MODIFYING ANTIRHEUMATIC DRUG; INTERLEUKIN 6; METHOTREXATE; TOCILIZUMAB;

AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DAS28; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG EXPOSURE; DRUG POTENCY; DRUG RESPONSE; HUMAN; MAJOR CLINICAL STUDY; MONOTHERAPY; PHARMACODYNAMICS; PHASE 3 CLINICAL TRIAL (TOPIC); REMISSION; RHEUMATOID ARTHRITIS; STEADY STATE;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIRHEUMATIC AGENTS; ARTHRITIS, RHEUMATOID; BLOOD SEDIMENTATION; C-REACTIVE PROTEIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; MALE; METHOTREXATE; MODELS, BIOLOGICAL; RECEPTORS, INTERLEUKIN-6; SERUM AMYLOID A PROTEIN; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 84877871136     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270012437585     Document Type: Article

References (21)

1. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol . 2007;7:429-442.
2. Lipsky PE. Interleukin-6 and rheumatic diseases. Arthritis Res Ther . 2006;8(suppl):S4.
3. Madhok R, Crilly A, Watson J, Capell HA. Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis . 1993;52:232-234.
4. Dasgupta B, Corkill M, Kirkham B, Gibson T, Panayi G. Serial estimation of interleukin 6 as a measure of systemic disease in rheumatoid arthritis. J Rheumatol . 1992;19:22-25.
5. Sack U, Kinne RW, Marx T, Heppt P, Bender S, Emmrich F. Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol Int . 1993;13:45-51.
6. Kotake S, Sato K, Kim KJ, et al. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J Bone Miner Res . 1996;11:88-95.
7. Mihara M, Kasutani K, Okazaki M, et al. Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol . 2005;5:1731-1740.
8. Nishimoto N, Miyasaka N, Yamamoto K, et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol . 2009;19:12-19.
9. Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J. Long-term safety and efficacy of tocilizumab, an antiinterleukin-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis . 2008;68:1580-1584.
10. Nishimoto N, Hashimoto J, Miyasaka N, et al. Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis . 2007;66:1162-1167.
11. Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum . 2006;54:2817-2829.
12. Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis . 2010;69:88-96.
13. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet . 2008;371:987-997.
14. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the Tocilizumab in Combination with Traditional Disease-Modifying Antirheumatic Drug Therapy Study. Arthritis Rheum . 2008;58:2968-2980.
15. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis . 2008;67:1516-1523.
16. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Guidance for Industry: Population Pharmacokinetics . http://www.fda.gov/Downloads/Drugs/Guidancecomplianceregulatoryinformation/ Guidances/Ucm072137.pdf. Accessed November 21, 2011.
17. Prevoo MLL, van 't Hof H, Kuper H, van Leeuwen MA, van de Putte LBA, van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts. Arthritis Rheum . 1995:38:44-48.
18. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum . 1993:36:729-740.
19. Frey N, Grange S, Woodworth T. Population pharmacokinetic analysis of tocilizumab in patients with rheumatoid arthritis. J Clin Pharmacol . 2010;50:754-766.
20. van Gestel AM, Prevoo MLL, van 't Hof MA, van Rijswijk MH, van de Putte LBA, van Riel PLCM. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis: comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism criteria. Arthritis Rheum . 1996;39:34-40.
21. Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood . 2008;112:3959-3964.