Tocilizumab for the Treatment of AA Amyloidosis

Tanaka, Toshio; Hagihara, Keisuke; Hishitani, Yoshihiro; Ogata, Atsushi

doi:10.5772/20245

Cited by 9 publications

(5 citation statements)

References 49 publications

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“…The pleiotropic activity of IL-6 also indicates that IL-6 blockade represents a rational treatment strategy for various diseases. A good example of the efficacy of such treatment is the dramatic improvement engendered by tocilizumab in amyloid A amyloidosis and anemia of inflammation through inhibition of their respective responsible proteins, SAA and hepcidin synthesis 151 , 152 . However, the mechanisms through which tocilizumab exerts its therapeutic effects on various phenotypically different autoimmune and inflammatory diseases are not yet well understood.…”

Section: Future Directionsmentioning

confidence: 99%

Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases

Tanaka¹,

2012

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Interleukin (IL)-6, a cytokine featuring redundancy and pleiotropic activity, contributes to host defense against acute environmental stress, while dysregulated persistent IL-6 production has been demonstrated to play a pathological role in various autoimmune and chronic inflammatory diseases. Targeting IL-6 is thus a rational approach to the treatment of these diseases. Indeed, clinical trials of tocilizumab, a humanized anti-IL-6 receptor antibody have verified its efficacy and tolerable safety for patients with rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for treatment of these diseases. Moreover, a considerable number of case reports and pilot studies of off-label use of tocilizumab point to the beneficial effects of tocilizumab for a variety of other phenotypically different autoimmune and chronic inflammatory diseases. Elucidation of the source of IL-6 and of mechanisms through which IL-6 production is dysregulated can thus be expected to lead to clarification of the pathogenesis of various diseases.

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Section: Future Directionsmentioning

confidence: 99%

Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases

Tanaka¹,

2012

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“…Because the synthesis of SAA depends primarily on IL-6, TCZ injection promptly reduces the serum concentration of SAA, just as in the case of C-reactive protein, and the suppressive activity of TCZ on the serum SAA level is more powerful than that of TNF inhibitors. 88 , 89 Case reports and series studies published to date have demonstrated the marked ameliorative effect of TCZ on gastrointestinal symptoms and renal dysfunction caused by amyloid A amyloidosis. 90 – 92 …”

Section: Conclusion and Place In Therapymentioning

confidence: 99%

Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors

Tanaka¹,

Hishitani²,

Ogata³

2014

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation, systemic inflammation, and immunological abnormalities. Because cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 play a major role in the development of RA, their targeting could constitute a reasonable novel therapeutic strategy for treating RA. Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs) including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs). Although bDMARDs have elicited to a paradigm shift in the treatment of RA due to the prominent efficacy that had not been previously achieved by sDMARDs, a substantial percentage of patients failed primary or secondary responses to bDMARD therapy. Because RA is a heterogeneous disease in which TNF-α and IL-6 play overlapping but distinct pathological roles, further studies are required to determine the best use of TNF inhibitors and tocilizumab in individual RA patients.

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“…217,219 This suggests that IL-6 blocking may be an innovative strategy for amyloid A amyloidosis complicated with chronic inflammatory diseases. 223…”

Section: Additional Applications Of Tocilizumab For Other Immune-medimentioning

confidence: 99%

Tocilizumab: An Updated Review of Its Use in the Treatment of Rheumatoid Arthritis and Its Application for Other Immune-Mediated Diseases

Tanaka

Ogata

Narazaki

2013

Clinical Medicine Insights: Therapeutics

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Interleukin-6 (IL-6), produced by a variety of cells, is a typical cytokine featuring redundancy and pleiotropic activity. IL-6 is promptly and transiently synthesized in response to infections or injuries, and participates in host defense by inducing immune responses, hematopoiesis, and acute-phase reactions. However, since its abnormal persistent production of mostly unknown etiology plays an important pathological role in the development of various immune-mediated diseases, a humanized anti-IL-6 receptor monoclonal antibody, tocilizumab, was developed and is now used as an innovative biologic for rheumatoid arthritis in more than 90 countries. Several factors strongly suggest that a IL-6 blockade strategy may have a broad application for the treatment of various immune-mediated diseases. These factors include favorable results of pilot or case studies with off-label use of tocilizumab, pathological analyses of the contribution of IL-6 to the development of immune-mediated diseases, and the potential capability of tocilizumab to both repair an imbalance of effector T cell subsets and to suppress pathologic autoantibody production. However, clinical trials to evaluate the efficacy and safety of tocilizumab for these diseases are essential. Furthermore, clarification of the cell source of IL-6 production and of the mechanisms through which dysregulated continuous IL-6 synthesis is induced constitutes an important issue for future studies into the pathogenesis of diseases.

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Tocilizumab for the Treatment of AA Amyloidosis

Cited by 9 publications

References 49 publications

Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases

Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases

Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors

Tocilizumab: An Updated Review of Its Use in the Treatment of Rheumatoid Arthritis and Its Application for Other Immune-Mediated Diseases

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