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IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial
  1. P Emery1,
  2. E Keystone2,
  3. H P Tony3,
  4. A Cantagrel4,
  5. R van Vollenhoven5,
  6. A Sanchez6,
  7. E Alecock7,
  8. J Lee8,
  9. J Kremer9
  1. 1 Leeds Teaching Hospitals Trust, University of Leeds, Leeds, UK
  2. 2 Mount Sinai Hospital, Toronto, Canada
  3. 3 Medizinische Klinik II, Würzburg, Germany
  4. 4 Hôpital Rangueil, Toulouse, France
  5. 5 Karolinska University Hospital, Stockholm, Sweden
  6. 6 Hospital de Especialidades, Guadalajara, Mexico
  7. 7 Roche Products Ltd, Welwyn, UK
  8. 8 Roche Products Inc, Nutley, New Jersey, USA
  9. 9 Albany Medical College, Albany, New York, USA
  1. Professor P Emery, Academic Section of Musculoskeletal Disease, 2nd Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK; p.emery{at}leeds.ac.uk

Abstract

Objectives: The phase III RADIATE study examined the efficacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with rheumatoid arthritis (RA) refractory to tumour necrosis factor (TNF) antagonist therapy.

Methods: 499 patients with inadequate response to one or more TNF antagonists were randomly assigned to receive 8 mg/kg or 4 mg/kg tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks. ACR20 responses, secondary efficacy and safety endpoints were assessed.

Results: ACR20 was achieved at 24 weeks by 50.0%, 30.4% and 10.1% of patients in the 8 mg/kg, 4 mg/kg and control groups, respectively (less than p<0.001 both tocilizumab groups versus control). At week 4 more patients achieved ACR20 in 8 mg/kg tocilizumab versus controls (less than p = 0.001). Patients responded regardless of most recently failed anti-TNF or the number of failed treatments. DAS28 remission (DAS28 <2.6) rates at week 24 were clearly dose related, being achieved by 30.1%, 7.6% and 1.6% of 8 mg/kg, 4 mg/kg and control groups (less than p = 0.001 for 8 mg/kg and p = 0.053 for 4 mg/kg versus control). Most adverse events were mild or moderate with overall incidences of 84.0%, 87.1% and 80.6%, respectively. The most common adverse events with higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash and headache. The incidence of serious adverse events was higher in controls (11.3%) than in the 8 mg/kg (6.3%) and 4 mg/kg (7.4%) groups.

Conclusion: Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety profile.

Trial registration number: NCT00106522.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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Footnotes

  • Funding: Grant support was received from F Hoffmann-La Roche Ltd and Chugai Pharma KK.

  • Competing interests: PE, EK, RvV and JK have received research grants from F Hoffmann-La Roche Ltd. PE, RvV and JK have received consulting fees from F Hoffmann-La Roche Ltd. EA and JL are employees of Roche Products.

  • Ethics approval: Protocol approval by institutional review boards, ethics committees and/or regulatory authorities was obtained.

  • Patient consent: Obtained.

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