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Giant cell arteritis (GCA), also known as temporal arteritis, is a chronic vasculitis of medium and large vessels that occurs in individuals older than 50 years of age. Many manifestations of GCA result from vascular inflammation involving cranial branches of the arteries that originate from the aortic arch.1
Glucocorticoid (GC) treatment is usually instituted once the diagnosis is confirmed by temporal artery biopsy, or when clinical suspicion for GCA is high and the patient is at high risk for vascular complications. GCs can reduce the symptoms of GCA, and decrease the risk for vascular complications.2
GC use is associated with an increased risk of serious adverse cardiovascular events, particularly ischemic heart disease and heart failure.3 Therefore, one treatment goal in GCA is early GC tapering and, when possible, transitioning to GC-sparing medication while maintaining low, controlled disease activity. However, GCA disease relapses have been noted when GC doses are tapered, which can result in re-treatment with higher doses of GC. These doses may be associated with increased complications including diabetes mellitus, osteoporotic fracture, cataracts, and increased infection risk.3
In patients whose risk stratification for adverse effects of GCs is very high, or in patients unable to continue taking GCs, interleukin (IL)-6 blockers like tocilizumab (TCZ) have been used. TCZ, a humanized monoclonal antibody against the IL-6 receptor, has been shown to induce rapid decreases in disease activity in patients with GCA.4
To investigate the feasibility of utilizing TCZ in the induction and maintenance of remission of GCA in patients with newly diagnosed or recurrent GCA, Peter Villiger, MD, and colleagues from the University Hospital at the University of Bern, Bern, Switzerland conducted a randomized, double-blind, placebo-controlled trial studying the safety and efficacy of TCZ in patients meeting the American College of Rheumatology (ACR) criteria for GCA.5
Thirty patients were randomly assigned (2:1) to receive intravenous infusion of either TCZ (8 mg/kg) or placebo every 4 weeks for a year. Both groups of patients were initially treated with high-dose prednisolone (1 mg/kg/day) and weaned off using a predetermined standardized dose-reduction specified by the approved study protocol.
The primary outcome was defined as complete disease remission at a prednisolone dose of 0.1 mg/kg per day at the 3-month mark. Secondary outcome measures were defined as time to relapse after induction, cumulative doses of GC (mg), and proportion of patients who maintain remission without relapse.
Complete remission at 3 months was achieved in 17 (85%) of 20 patients given TCZ and 4 (40%) of 10 patients given placebo (P=.03). Seventeen (85%) patients in the TCZ group reached complete remission by 3 months compared with 2 (20%) patients in the placebo group by 52 weeks (P=.001).
Patients on TCZ were also more likely to have been tapered completely off GCs at month 3, after receiving a lower cumulative dose of prednisolone (43 mg/kg) compared to those on placebo (110 mg/kg) after 1 year (P=.001).
Adverse effects, largely related to GC side effects, were seen in 7 (35%) patients in the TCZ group and 5 (50%) in the placebo group.
Summary and Clinical Applicability
One of the most challenging aspects of managing GCA is identifying an appropriate GC taper regimen, while recognizing and managing any GCA flares that may result in this time period. This was the first randomized, placebo-controlled trial showing the efficacy and safety of using TCZ for GCA treatment induction and remission.
Reference
1. Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med. 2003;349(2):160-9.
2. Lundberg I, Hedfors E. Restricted dose and duration of corticosteroid treatment in patients with polymyalgia rheumatica and temporal arteritis. J Rheumatol. 1990;17(10):1340-5.
3. Huscher D, Thiele K, Gromnica-ihle E, et al. Dose-related patterns of glucocorticoid-induced side effects. Ann Rheum Dis. 2009;68(7):1119-24.
4. Evans J, Steel L, Borg F, Dasgupta B. Long-term efficacy and safety of tocilizumab in giant cell arteritis and large vessel vasculitis. RMD Open. 2016;2(1):e000137.
5. Villiger PM, Adler S, Kuchen S, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. Published Online First March 4, 2016.
