Overview. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA). Design. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids. Conclusion. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development. 1. Introduction Giant cell arteritis (GCA, temporal arteritis) is an inflammatory disease of medium- and large-sized arteries that affects individuals older than 50 years of age [1]. The disease commonly involves the aorta, great vessels, and the extracranial branches of the carotid arteries. GCA is the most common primary form of vasculitis in Western countries and has a prevalence that ranges from 24 to 280 cases per 100,000 in individuals older than 50 years [2–4]. Its clinical presentation consists of constitutional symptoms, headaches, ischemia-related visual manifestations, jaw claudication, and polymyalgia rheumatica. The inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) are elevated in the vast majority of the cases during active disease [5]. GCA and its current treatment strategies carry a substantial morbidity burden. The most feared consequence of the disease is blindness [6], but multiple complications can ensue (e.g., tongue necrosis, aortic aneurysm, stroke, or myocardial infarction). Corticosteroids (CS), the mainstay of treatment, control systemic inflammation effectively and prevent acute damage (i.e., vision loss) but generally fail to cure GCA or induce long-term CS-free remissions. Fifty to 80%
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