Review of tocilizumab in the treatment of rheumatoid arthritis

Figures & data

Figure 1 Pathological roles of interleukin-6 in rheumatoid arthritis. Constitutive overproduction of interleukin-6, a pleiotropic cytokine that regulates the immune system, inflammation, hematopoiesis, and bone metabolism, is thought to play pathologic roles in rheumatoid arthritis.

Abbreviations: VEGF, vascular endothelial growth factor; ICAM-1, intercellular adhesion molecule-1; Th17, interleukin-17 producing CD4+ T cell; Treg, CD4+CD25+ regulatory T cell; RF, rheumatoid factor; CRP, C-reactive protein; SAA, serum amyloid A; RBC, red blood cell.

Figure 2 Signal transduction of interleukin (IL)-6 /IL-6 receptor (R) complex via gp130 and the mechanism of signal transduction blockage by tocilizumab. IL-6 signal is mediated via IL-6R on the cell surface or soluble form of IL-6R, followed by dimerization of the signal transducer gp-130, which is bound to the IL-6/IL-6R complex. Tocilizumab inhibits the binding of IL-6 to IL-6R or sIL-6R.

Figure 3 The incidence of a 20% improvement in disease activity according to the American College of Rheumatology (ACR) criteria at week 12. Tocilizumab treatment significantly improved all measures of disease activity in the ACR core set, and a dose-response relationship was observed between the 4-mg and 8-mg groups. Adapted with permission from Nishimoto N, Yoshizaki K, Miyasaka N, et al. 2004. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum, 50:1761–9. Copyright © 2004. Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.

Abbreviation: TOC, tocilizumab.

Table 1 DAS28 remission (<2.6)% improvement scores among tocilizumab’s clinical studies. Tocilizumab treatment significantly improved the measures of DAS28 scores compared to the control group. Adapted from Nishimoto et al (2006b)

	Late P II		SATORI		SAMURAI
	T	C	T	C	T	C
12 weeks	18.2	0	34.3	1.6	29.3	1.4
24 weeks	N.A	N.A	41.0	1.6	40.1	4.1
52 weeks	N.A	N.A	N.A	N.A	58.6	3.4

Notes: SATORI = Study of active controlled monotherapy for rheumatoid arthritis patients with inadequate response to methotrexate; SAMURAI = Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor.

NishimotoNYoshizakiKMiyasakaN2004Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trialArthritis Rheum501761915188351

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NishimotoNMiyasakaNYamamotoK2006bConsistent clinical response resulted from three Japanese randomized controlled trials of tocilizumab, humanized anti-IL-6 receptor antibody, in active rheumatoid arthritis (RA) patientsArthritis Rheum54S410

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