Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial
Abstract
Background Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis.Methods In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137.Results Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events.Interpretation Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis.Funding Roche and the University of Bern.
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Two randomized controlled trials showed efficacy of tocilizumab for induction and maintenance of remission in patients with new-onset and relapsing giant cell arteritis.
“Two RCTs recently showed the efficacy of TCZ for the induction and maintenance of remission in patients with new-onset and relapsing GCA.97,98”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [98]
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- Authors
- Villiger, P. M., Adler, S., Kuchen, S., Wermelinger, F., Dan, D., Fiege, V., Bütikofer, L., Seitz, M., & Reichenbach, S.
- Affiliations
- University of Bern (CH)
- Corresponding author
- Villiger, Peter M
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 387
- Issue
- 10031
- Pages
- 1921-1927
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2292169217
- Cited by
- 577
- References
- 29
- Citations by year
- 2026: 24 · 2025: 37 · 2024: 57 · 2023: 44 · 2022: 59 · 2021: 72 · 2020: 55 · 2019: 62 · 2018: 65 · 2017: 71 · 2016: 29
- FWCI
- 67.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- giant cell arteritis, tocilizumab, IL-6 receptor, remission induction, remission maintenance, prednisolone, steroid-sparing therapy, monoclonal antibodies, treatment efficacy and safety, elderly patients, disease activity assessment, erythrocyte sedimentation rate, C-reactive protein
- MeSH terms
- Aged, Anti-Inflammatory Agents, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Prednisolone, Giant Cell Arteritis, Treatment Outcome, Disease-Free Survival, Maintenance Chemotherapy, Induction Chemotherapy, Antibodies, Monoclonal, Humanized
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