title: Tocilizumab in the treatment of rheumatoid arthritis and beyond.
abstract: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Hanson
authors.affiliation: Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Korsten
authors.affiliation: Anesthesia and Pain Management, King Hussein Cancer Center, Amman, Jordan.
authors.forename: Munir
authors.initials: M
authors.lastname: Shawagfeh
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Shiva
authors.initials: S
authors.lastname: Arami
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Suncica
authors.initials: S
authors.lastname: Volkov
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Vila
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: William
authors.initials: W
authors.lastname: Swedler
authors.affiliation: Liver Transplant, Kidney Transplant Royal Medical Services, Jordan.
authors.forename: Abdel Naser
authors.initials: AN
authors.lastname: Shunaigat
authors.affiliation: Liver Transplant, Kidney Transplant Royal Medical Services, Jordan.
authors.forename: Sameer
authors.initials: S
authors.lastname: Smadi
authors.affiliation: Cardiac Surgery Methodist Hospitals, Merrillville, IN, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Sawaqed
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Perkins
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahrara
authors.affiliation: Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Nadera J
authors.initials: NJ
authors.lastname: Sweiss
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology; D004359:Drug Therapy, Combination; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab
keywords: IL-6; biologics; rheumatoid arthritis; tocilizumab
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