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N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849.

Trial of Tocilizumab in Giant-Cell Arteritis.

Author information

1
From the Massachusetts General Hospital Rheumatology Unit, Harvard Medical School, Boston (J.H.S., S.H.U.); Roche Products, Welwyn Garden City (K.T., S.D., N.C.), and Southend University Hospital NHS Foundation Trust, Westcliff-on-Sea (B.D.) - both in the United Kingdom; Genentech, South San Francisco, CA (M.K.); the Department of Rheumatology, Medicine III, University Medical Center and Faculty of Medicine Technische Universität Dresden, Dresden (M.A.), Friedrich-Alexander-University Erlangen-Nürnberg, Department of Internal Medicine 3-Rheumatology and Immunology (J.R.), and Institute of Clinical Immunology (G.S.), Universitätsklinikum Erlangen, Erlangen, and the Division of Rheumatology and Clinical Immunology, Department of Medicine IV, University of Munich, Munich (H.S.-K.) - all in Germany; the Department of General Internal Medicine, University Hospitals Gasthuisberg, Leuven, Belgium (D.B.); the Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center, Groningen, the Netherlands (E.B.); the Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona (M.C.C.); the Division of Internal Medicine, Azienda Ospedaliera-Istituto di Ricovero e Cura a Carattere Scientifico di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Italy (C.S.); and Hospital for Special Surgery, New York (R.S.).

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 .).

PMID:
28745999
DOI:
10.1056/NEJMoa1613849
[Indexed for MEDLINE]
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