Article

Tocilizumab for the Treatment of Juvenile Idiopathic Arthritis

Baystate Medical Center, Springfield, MA, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 05/2012; 46(6):822-9. DOI: 10.1345/aph.1Q756
Source: PubMed

ABSTRACT

To evaluate the pharmacology, clinical efficacy, safety, and role of tocilizumab for the treatment of juvenile idiopathic arthritis.
A literature search via MEDLINE through PubMed (1970-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was performed to identify clinical trials and review articles. The key search terms tocilizumab, anti-interleukin 6, and juvenile idiopathic arthritis were used, with several combinations of terms. Bibliographies of selected articles were examined to identify additional references, and ongoing trials were identified through a review of www.clinicaltrials.gov.
Articles were limited to those published in English and studies in humans. Studies included in the review examined pediatric data in systemic and polyarticular juvenile idiopathic arthritis. Background information was obtained through reviews of literature on a wide variety of autoimmune disease states in both adult and pediatric populations.
Tocilizumab is Food and Drug Administration-approved for use in patients aged 2 years and older with systemic juvenile idiopathic arthritis. Tocilizumab was superior to placebo in triggering a symptomatic response during Phase 2 and 3 clinical trials. Tocilizumab was determined to be safe, with only a small number of serious adverse drug events occurring within studies.
Tocilizumab provides expansion of the available options for the treatment of systemic juvenile idiopathic arthritis, specifically in patients who have not responded to conventional therapies. Tocilizumab is relatively well tolerated and has proven efficacy for up to 52 weeks. Further studies are warranted to determine its utility as a first-line option for systemic juvenile idiopathic arthritis as well as its role within the treatment of polyarticular juvenile idiopathic arthritis.

Download full-text

Full-text

Available from: Evan R Horton, Nov 21, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in acute inflammation. It is secreted by T cells and macrophages during infection and after trauma. It is responsible for activation of B cells and other immune cells. Its importance was also described in regeneration of some tissues (e.g. liver). In these above named roles IL-6 is essential for physiological functions of human immunity and organs and it is responsible for maintenance of the integrity of macroorganisms. The pathological role of IL-6 starts with the transition of acute inflammation into chronic inflammation. Several types of chronic inflammation - differing by cause, mechanism, outcome, intensity and duration - can promote chronic diseases and also cancer development and progression. Some chronic inflammatory diseases increase the risk of cancer. A typical example is chronic hepatitis or inflammatory bowel diseases, where we could observe a connection with hepatocellular carcinoma or colorectal cancer. There, IL-6 is also responsible for tumor growth, invasion, metastasis and angiogenesis. The other chronic diseases that are related with IL-6 are psoriasis or rheumatoid arthritis which can't turn into malignant diseases. The role of IL-6 was proved by many experimental animal models with knock-out genes for IL-6 or its receptors. Many homozygotes showed the symptoms of named chronic diseases or had increased risk of malignant transformation. In case of substitution of IL-6, normalization of symptoms of chronic diseases were observed or the risk of malignant transformation was decreased. This led scientists to design monoclonal antibodies against IL-6 or its receptor. Some of them were used in clinical trials and their effect is now under evaluation. Anti-IL-6 chimeric monoclonal antibody Siltuximab was administered to patients with metastasizing renal cell carcinoma or prostate cancer, ovarian cancer, etc. Anti-IL-6 receptor monoclonal antibody Tocilizumab was demonstrated to be effective in the treatment of rheumatoid arthritis, Castleman's disease or juvenile idiopathic arthritis. The aim of this paper is to present contemporarily known IL-6 inhibitors, explain their function and blockage of physiological and pathophysiological pathways and their relation to the broad spectrum of benign and malignant diseases with special regard to treatment strategies using IL-6 inhibitors in clinical trials or as approved drugs by national authorization committees.
    No preview · Article · Jan 2013 · Proteomics Research Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays an important role in acute inflammation. It is secreted by T cells and macrophages during infection and after trauma. It is responsible for activation of B cells and other immune cells. Its importance was also described in regeneration of some tissues (e.g. liver). In these above named roles IL-6 is essential for physiological functions of human immunity and organs and it is responsible for maintenance of the integrity of macroorganisms. The pathological role of IL-6 starts with the transition of acute inflammation into chronic inflammation. Several types of chronic inflammation - differing by cause, mechanism, outcome, intensity and duration - can promote chronic diseases and also cancer development and progression. Some chronic inflammatory diseases increase the risk of cancer. A typical example is chronic hepatitis or inflammatory bowel diseases, where we could observe a connection with hepatocellular carcinoma or colorectal cancer. There, IL-6 is also responsible for tumor growth, invasion, metastasis and angiogenesis. The other chronic diseases that are related with IL-6 are psoriasis or rheumatoid arthritis which cańt turn into malignant diseases.The role of IL-6 was proved by many experimental animal models with knock-out genes for IL-6 or its receptors. Many homozygotes showed the symptoms of named chronic diseases or had increased risk of malignant transformation. In case of substitution of IL-6, normalization of symptoms of chronic diseases were observed or the risk of malignant transformation was decreased. This led scientists to design monoclonal antibodies against IL-6 or its receptor. Some of them were used in clinical trials and their effect is now under evaluation. Anti-IL-6 chimeric monoclonal antibody Siltuximab was administered to patients with metastasizing renal cell carcinoma or prostate cancer, ovarian cancer, etc. Anti-IL-6 receptor monoclonal antibody Tocilizumab was demonstrated to be effective in the treatment of rheumatoid arthritis, Castlemańs disease or juvenile idiopathic arthritis. The aim of this paper is to present contemporarily known IL-6 inhibitors, explain their function and blockage of physiological and pathophysiological pathways and their relation to the broad spectrum of benign and malignant diseases with special regard to treatment strategies using IL-6 inhibitors in clinical trials or as approved drugs by national authorization committees.
    No preview · Article · Apr 2013
  • [Show abstract] [Hide abstract]
    ABSTRACT: Systemic sclerosis is an autoimmune disorder with an unknown cause. The cardinal features of the disease are autoimmunity, vasculopathy, inflammation and fibrosis. There appears to be a link between inflammation and inflammatory cells and the uncontrolled deposition of the extracellular matrix. In particular, T cells appear to play a prominent role in disease initiation and propagation through the secretion of a myriad of cytokines and growth factors. These T-cell-dependent products may drive the proliferation and activation of resident fibroblasts, which ultimately leads to fibrosis. This review summarizes the current literature of the role of T cells in systemic sclerosis and suggests that therapeutic targeting of T cells is a promising new avenue.
    No preview · Article · Jun 2013
Show more