Tocilizumab: A Review of Its Use in the Treatment of Juvenile Idiopathic Arthritis

Abstract

Tocilizumab (RoActemra(®); Actemra(®)) is a recombinant humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist. Both in the US and EU, tocilizumab has been approved for the treatment of two subtypes of juvenile idiopathic arthritis (JIA), namely systemic JIA (sJIA) and polyarticular JIA (pJIA), in patients aged ≥2 years. These approvals are based on favorable results from two randomized, double-blind, placebo-controlled, multinational, phase III trials in which patients aged 2-17 years with active sJIA (TENDER) or pJIA (CHERISH) received an intravenous dose of tocilizumab based on bodyweight every 2 or 4 weeks, respectively. Tocilizumab met the primary endpoint in both of these ongoing, multi-part studies. That is, in TENDER, significantly more tocilizumab recipients than placebo recipients achieved a JIA American College of Rheumatology (ACR) 30 response plus absence of fever, as assessed at the end of a 12-week double-blind treatment period, while in CHERISH, significantly fewer tocilizumab recipients than placebo recipients experienced a JIA ACR 30 flare during a 24-week double-blind withdrawal period (all patients had previously received open-label tocilizumab in a 16-week lead-in phase). Tocilizumab was generally well tolerated in the TENDER trial. Infections (e.g. upper respiratory tract infection and pharyngitis or nasopharyngitis) accounted for just over one-third of all reported adverse events in this trial; tocilizumab-treated patients appeared to have an approximately 11 % risk of a serious infection per year of treatment. Clinical laboratory abnormalities included neutropenia and elevated aminotransferase levels. The tolerability profile of tocilizumab in CHERISH was generally consistent with that of the drug in TENDER.

Therapeutic Potential of IL‐17‐Mediated Signaling Pathway in Autoimmune Liver Diseases

“…Antagonistical antibody against the interleukin 6 receptor (tocilizumab) demonstrates significant clinical efficacy and satisfying safety; hence tocilizumab has been approved in many countries for the treatment of certain inflammatory autoimmune diseases such as RA and juvenile idiopathic arthritis (JIA) [117, 118]. In addition, IL-1 β is another crucial cytokine for IL-17 induction.…”

Cytokine profiles in pediatric multiple sclerosis

“…In contrast, serum IL-6 appears to correlate positively with disease activity in other inflammatory childhood diseases such as Kawasaki disease, juvenile inflammatory arthritis (JIA), and ulcerative colitis [16][17][18]. Indeed, anti-IL-6 therapy is currently in use for JIA [19]. IL-6 is a multifunctional cytokine produced by many cell types in response to infection, but also plays a pro-inflammatory role in incurring EAE [20][21][22].…”

Experience of Parenteral Administration of Methotrexate in a Female Patient Suffering from Early Juvenile Idiopathic Arthritis and Uveitis

“…[27]. Новые данные показали, что комбинированное при-менение ГИБП с метотрексатом повышает их эффектив-ность, в частности усиливает их положительное влияние на деструкцию суставов [28,29].…”