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Trial of Tocilizumab in Giant-Cell Arteritis

Published on Jul 27, 2017in The New England Journal of Medicine70.67
· DOI :10.1056/NEJMoa1613849
John H. Stone70
Estimated H-index: 70
(Harvard University),
Katie Tuckwell8
Estimated H-index: 8
(Hoffmann-La Roche)
+ 13 AuthorsNeil Collinson9
Estimated H-index: 9
(Hoffmann-La Roche)
Abstract
BackgroundGiant-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. MethodsIn 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 an...
  • References (36)
  • Citations (207)
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References36
Newest
#1Katie Tuckwell (Hoffmann-La Roche)H-Index: 8
#2Neil Collinson (Hoffmann-La Roche)H-Index: 9
Last. John H. Stone (Harvard University)H-Index: 70
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Abstract Objective To report entry criteria and clinical features of patients with newly diagnosed and relapsing giant cell arteritis (GCA) enrolled in a randomized trial of tocilizumab, an interleukin-6 receptor-alpha inhibitor. Methods Newly diagnosed GCA was defined as diagnosis ≤6 weeks before baseline. Relapsing GCA was defined as diagnosis >6 weeks before baseline with ≥2 consecutive weeks of prednisone ≥40 mg/day. All patients had active GCA within 6 weeks of baseline. All statistical res...
17 CitationsSource
#1Alexis Régent (Paris V: Paris Descartes University)H-Index: 12
#2S. RedekerH-Index: 2
Last. Eric ToussirotH-Index: 33
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Objective. To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA). Methods. A retrospective multicenter study that included 34 patients receiving TCZ for GCA. Results. TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 ± 1.3 mont...
28 CitationsSource
#1Christian Dejaco (University of Graz)H-Index: 27
#2Christina DuftnerH-Index: 24
Last. Bhaskar DasguptaH-Index: 35
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46 CitationsSource
#1John SchmidtH-Index: 6
#2Amar SmailH-Index: 12
Last. Pierre DuhautH-Index: 29
view all 6 authors...
Objective To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis (GCA). Methods In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age- and sex-matched subjects were randomly selected from the general population and matched to patients at the time...
26 CitationsSource
Abstract This article critically reviews the advances in medical management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) with a focus on recent developments in targeted biologic therapy. The role of biologics in the treatment of large vessel vasculitis (LVV) is expanding. TNFα inhibitors appear to be effective in the treatment of TAK but have little benefit in GCA. Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA. Increasing o...
31 CitationsSource
#1Peter M. Villiger (University of Bern)H-Index: 44
#2Sabine Adler (University of Bern)H-Index: 10
Last. Stephan Reichenbach Oberarzt (University of Bern)H-Index: 36
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#1John Schmidt (French Institute of Health and Medical Research)H-Index: 6
#2Amar SmailH-Index: 12
Last. P. Duhaut (French Institute of Health and Medical Research)H-Index: 1
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#1Jobie EvansH-Index: 1
#2Lauren SteelH-Index: 2
Last. Bhaskar Dasgupta (ARU: Anglia Ruskin University)H-Index: 35
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Giant cell arteritis (GCA) is a chronic systemic vasculitis affecting large-sized and medium-sized vessels. Glucocorticoids are currently the mainstay of treatment for GCA and associated large vessel vasculitis (LVV) but are associated with frequent adverse events. Methotrexate has only demonstrated a modest benefit while anti-TNF biological agents (infliximab and etanercept) have been inefficacious. Elevated levels of interleukin-6 (IL-6), a proinflammatory cytokine, has been associated with GC...
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#2Ricardo Blanco (UC: University of Cantabria)H-Index: 37
Last. Miguel A. Gonz (UC: University of Cantabria)H-Index: 73
view all 23 authors...
Abstract Objective To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. Methods A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. Results The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical featu...
70 CitationsSource
#1Tanaz A. Kermani (Mayo Clinic)H-Index: 18
#2Kenneth J. Warrington (Mayo Clinic)H-Index: 33
Last. Steven R. Ytterberg (Johns Hopkins University)H-Index: 40
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Objective. To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA). Methods. Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity. Results. The study included 128 subjects: 102 women (80%) and 26 men (20%). Mean ± SD age at diagnosis of GCA was 69.9 ± 8.6 years. Mean followup for the cohort w...
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#1C Ponte (IMM: Instituto de Medicina Molecular)H-Index: 4
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BACKGROUND: The vasculitides are a group of rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is a web-based electronic clinical record, created in 2008, which currently includes specific modules for 12 diseases and > 20,000 patients registered from 79 rheumatology centres. On October 2014, a dedicated module for vasculitis was created as part of the European Vascu...
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#1M Aitken (NHS Greater Glasgow and Clyde)
#2Neil Basu (Glas.: University of Glasgow)H-Index: 15
Systemic vasculitis are a complex cluster of diseases with high associated morbidity. As disease-related mortality diminishes, the cumulative impact of poor health-related quality of life becomes more pertinent to patients than the initial pathological insult. In this article we explore health-related quality of life in ANCA-associated vasculitis, large-vessel vasculitis and therapeutic strategies that may enhance this critical outcome.
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#1Maria C. Cid (University of Barcelona)H-Index: 52
#2Roberto Ríos-Garcés (University of Barcelona)H-Index: 1
Last. Georgina Espígol-Frigolé (University of Barcelona)H-Index: 21
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For decades, the treatment of GCA has relied on glucocorticoids. Work over the past two decades has supported a modest efficacy of MTX but no clear benefit from anti-TNF-based therapies. More recently, the therapeutic armamentarium for GCA has expanded. The availability of agents targeting specific cytokines, cytokine receptors or signalling pathways, along with a better, although still limited, understanding of the immunopathology of GCA, are opening further therapeutic possibilities. Blocking ...
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#1Ernest Choy (Cardiff University)H-Index: 51
#2Fabrizio BenedettiH-Index: 61
Last. Tadamitsu Kishimoto (Osaka University)H-Index: 166
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In 1973, IL-6 was identified as a soluble factor that is secreted by T cells and is important for antibody production by B cells. Since its discovery more than 40 years ago, the IL-6 pathway has emerged as a pivotal pathway involved in immune regulation in health and dysregulation in many diseases. Targeting of the IL-6 pathway has led to innovative therapeutic approaches for various rheumatic diseases, such as rheumatoid arthritis, juvenile idiopathic arthritis, adult-onset Still’s disease, gia...
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Background: Giant cell arteritis (GCA) is the most common primary systemic vasculitis predominantly affecting large and medium sized vessels. In rare cases, the vasculitis can affect the vessels of the brain. Results: We describe four cases of GCA with involvement of the cerebral vessels causing stroke. These cases were unresponsive to aggressive immunosuppression and we opted to treat with endovascular balloon dilatation of the stenotic areas. The procedure was safe. The four patients were trea...
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BACKGROUND: Relapses frequently occur in giant cell arteritis (GCA), and long-term glucocorticoid therapy is required. The identification of associated factors with poor treatment outcomes is important to decide the treatment algorithm of GCA. METHODS: We enrolled 139 newly diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed with temporal artery biopsy, 1990 American College of Rheumatology classification cr...
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