Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review

Abstract

Tocilizumab, an anti-interleukin-6 (IL-6) agent, is indicated as a treatment for several autoimmune or inflammatory diseases, including rheumatoid arthritis and juvenile idiopathic arthritis (JIA). IL-6 plays roles in both immune system dysregulation and inflammation, and thus efforts to extend the utility of tocilizumab in patients with autoinflammatory conditions are ongoing. Here, we survey the literature on the off-label use of tocilizumab in patients with juvenile-onset rheumatic diseases including juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis (DM), vasculitis, juvenile scleroderma, and other autoinflammatory diseases. There is no real evidence that tocilizumab is useful for patients with SLE and juvenile DM, but several cases of childhood Takayasu arteritis have experienced promising outcomes. In juvenile-onset scleroderma, for which no therapy that can halt disease progression is available, tocilizumab may stop progression and the associated functional impairment. Tocilizumab prevents systemic inflammation in patients with Kawasaki’s disease, but may develop coronary aneurysms. Tocilizumab has been used to treat several pediatric autoinflammatory diseases, including JIA-associated uveitis and Castleman’s disease. Further work in larger populations is necessary to confirm the effects of tocilizumab in patients with pediatric rheumatic diseases.

Hypersensitivity Reactions to Monoclonal Antibodies in Children

“…All four patients had negative prick test but 3 of 4 had positive IDT. Tocilizumab has also been investigated in the off-label treatment of Takayasu arteritis in children and no ADR has been reported, while in other non-JIA rheumatic diseases some ADRs have been observed [58]. No HSR has been reported.…”

“…Chipps et al [65] and Rodrigo et al [66] found that anaphylaxis to omalizumab was rare. An incidence of 0.58% vs. placebo 1.04% (RR 0.51, p = 0.44) has been reported [58]. In the PROSE study [67] there were three anaphylaxes to omalizumab vs two for placebo and three for inhaled corticosteroids (ICS) boost.…”

Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis

“…Tocilizumab, intravenous (IV) or subcutaneous (SC) infusion, was the first drug approved by the Food and Drug Administration (FDA) respectively in 2010 and 2012, which resulted in rapid and sustained improvement in patients with RA. Tocilizumab was approved for use in children with polyarticular JIA as SC in 2013 [ 26 , 39 , 40 ].…”

Introduction on Monoclonal Antibodies

“…Tocilizumab or atlizumab (Actemra® or RoActemra®), is a humanized anti-IL-6 receptor mAb and binds to both soluble and membrane-bound IL-6 receptor. Its efficacy is currently being explored in the treatment of RA, systemic juvenile idiopathic arthritis in children, Castleman's disease, systemic lupus erythematosus (SLE), juvenile dermatomyositis (DM), vasculitis, and juvenile scleroderma [44]. Sarilumab (Kevzara®) is another human IgG1 mAb against IL-6 receptor developed for the treatment of RA [43].…”