Trial of tocilizumab in giant-cell arteritis

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • J. H. Stone - , Harvard University (Author)
  • K. Tuckwell - , Roche Products Limited UK (Author)
  • S. Dimonaco - , Roche Products Limited UK (Author)
  • M. Klearman - , Genentech Incorporated (Author)
  • M. Aringer - , Department of Internal Medicine III (Author)
  • D. Blockmans - , KU Leuven (Author)
  • E. Brouwer - , University of Groningen (Author)
  • M. C. Cid - , University of Barcelona (Author)
  • B. Dasgupta - , Mid and South Essex NHS Foundation Trust (Author)
  • J. Rech - , Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • C. Salvarani - , University of Modena and Reggio Emilia (Author)
  • G. Schett - , Scientific Research Institute of Clinical immunology (Author)
  • H. Schulze-Koops - , Friedrich-Alexander University Erlangen-Nürnberg, Ludwig Maximilian University of Munich (Author)
  • R. Spiera - , Hospital for Special Surgery (HSS) (Author)
  • S. H. Unizony - , Harvard University (Author)
  • N. Collinson - , Roche Products Limited UK (Author)

Abstract

BACKGROUND Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis. METHODS In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed. RESULTS Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week. CONCLUSIONS Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann–La Roche; ClinicalTrials.gov number, NCT01791153.).

Details

Original languageEnglish
Pages (from-to)317-328
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number4
Publication statusPublished - 27 Jul 2017
Peer-reviewedYes

External IDs

PubMed 28745999

Keywords

ASJC Scopus subject areas