Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement

Abstract

BackgroundSuppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications.ObjectiveTo review published evidence on safety and efficacy of IL-6i in inflammatory diseases.MethodsWe performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov.ResultsComprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable.ConclusionsIL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

“…Evidence has indicated that blocking the effects of IL-6 in RA is effective and safe, especially with the IL-6R inhibitor, tocilizumab [159] . Tocilizumab (Actemra ® ) is a humanized mAb of IgG1 class against IL-6R which prevents the formation of the IL-6/IL-6R complex and the activation of signal transduction cascade through JAKs and STATs.…”

Inflammation-Induced IL-6 Functions as a Natural Brake on Macrophages and Limits GN

“…The mAb tocilizumab, which is directed against the human IL-6R, is successfully used to treat rheumatoid arthritis and Still's disease. [16][17][18] However, some significant caveats remain. Besides its proinflammatory role, IL-6 signaling has also been shown to exert strong anti-inflammatory effects.…”

Retrospective Analysis of Efficacy and Safety of Tocilizumab Treatment in Children with Severe Systemic Juvenile Idiopathic Arthritis: 12-month Follow-up

“…Длительное применение глюкокортикоидов приводит к развитию тяжелых нежелательных явлений, а сни-жение дозы преднизолона -к очередному обостре-нию болезни. Достаточное число доказательств в пользу ведущей роли ИЛ 6 в патогенезе сЮИА позволили раз-работать и создать лекарство -тоцилизумаб -для лечения этого варианта ЮИА [5][6][7][8][9][10][11]. Результаты двух международных рандомизированных плацебоконтроли-руемых исследований показали высокую эффективность препарата для лечения как артрита, так и системных проявлений болезни, а также хороший профиль безопас-ности препарата [16,19].…”

“…Многие клинические и лабораторные проявления болезни при сЮИА обусловлены высоким содержани-ем интерлейкина (ИЛ) 6 в сыворотке крови и синови-альной жидкости [5][6][7][8][9][10][11]. С гиперпродукцией ИЛ 6 свя-зывают развитие таких внесуставных проявлений, как лихорадка и тромбоцитоз.…”