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 Schoels1,
- Désirée van der Heijde2,
- Ferdinand C Breedveld2,
- Gerd R Burmester3,
- Maxime Dougados4,
- Paul Emery5,
- Gianfranco Ferraccioli6,
- Cem Gabay7,
- Allan Gibofsky8,
- Juan Jesus Gomez-Reino9,
- Graeme Jones10,
- Tore K Kvien11,
- Miho M Murikama12,
- Norihiro Nishimoto12,
- Josef S Smolen1,13
- 12nd Department of Medicine, Center for Rheumatic Disease, Hietzing Hospital, Vienna, Austria
- 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
- 3Department of Rheumatology and Clinical Immunology, Charité, Free University and Humboldt University, Berlin, Germany
- 4Department of Rheumatology, Cochin Hospital, René Descartes University, Paris, France
- 5Academic Unit of Musculoskeletal Diseases, Leeds University, Leeds, UK
- 6Division of Rheumatology and Internal Medicine—CIC, Catholic University of the Sacred Heart—School of Medicine, Rome, Italy
- 7Division of Rheumatology, University Hospital, University of Geneva, Geneva, Switzerland
- 8Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA
- 9Department of Rheumatology Unit, Hospital Clinico Universitario, Santiago de Compostela, Santiago
- 10Musculoskeletal Unit, Menzies Research Institute, University of Tasmania, Hobart, Australia
- 11Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
- 12Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, Japan
- 13Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
- Correspondence to Dr Monika M Schoels, 2nd Department of Internal Medicine, Center for Rheumatic Diseases, Hietzing Hospital, Wolkersbergenstrasse 1, Vienna 1130, Austria;
- Accepted 14 October 2012
- Published Online First 10 November 2012
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.
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