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

Monika M Schoels, Désirée van der Heijde, Ferdinand C Breedveld, Gerd R Burmester, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Cem Gabay, Allan Gibofsky, Juan Jesus Gomez-Reino, Graeme Jones, Tore K Kvien, Miho Murakami, Norihiro Nishimoto, Josef S Smolen, Monika M Schoels, Désirée van der Heijde, Ferdinand C Breedveld, Gerd R Burmester, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Cem Gabay, Allan Gibofsky, Juan Jesus Gomez-Reino, Graeme Jones, Tore K Kvien, Miho Murakami, Norihiro Nishimoto, Josef S Smolen

Abstract

Background: Suppression 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.

Objective: To review published evidence on safety and efficacy of IL-6i in inflammatory diseases.

Methods: We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov.

Results: Comprehensive 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.

Conclusions: IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.

Figures

Figure 1
Figure 1
Search and selection process.AoSD, adult onset Still's disease; ACR, American College of Rheumatology conference, CLE, cutaneous lupus erythematosus;  EULAR, European League Against Rheumatism; IBD, inflammatory bowel disease; inhib., inhibitors, JIA, juvenile idiopathic arthritis; N, number; PMR, polymyalgia rheumatica; RA, rheumatoid arthritis, SpA, spondyloarthropathy; SLE, systemic lupus erythematosus; SSc, systemic sclerosis.
Figure 2
Figure 2
ACR20/50/70 response rates. (A) Comparison of tocilizumab monotherapy versus combination of tocilizumab with DMARDs. (B) Comparison of 4 mg/kg versus 8 mg/kg 4-weekly. Risk ratios and 95% CIs are displayed. RR>1 favour combination therapy (in panel A) or the 4 mg/kg TCZ dose (in panel B). ACR, American College of Rheumatology

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