WASHINGTON -- A combination of tocilizumab (Actemra) plus prednisone was superior to prednisone alone -- which formerly was the mainstay of treatment -- for achieving remission in giant cell arteritis (GCA), a phase III study showed.
"There is something new in giant cell arteritis at last, and the era of unending glucocorticoid treatment with no viable alternative is over," said , of Harvard Medical School, in a plenary session at the .
In a study that included 251 patients with GCA confirmed by temporal artery biopsy or cross-sectional imaging, patients were randomized to one of four groups: short-course prednisone (26 week taper) plus subcutaneous placebo; long-course prednisone (52-week taper) plus subcutaneous placebo; weekly subcutaneous tocilizumab, 162 mg, plus 26-week prednisone taper; or every other week tocilizumab, 162 mg, plus 26-week prednisone taper.
At month 12, 56% of patients receiving weekly tocilizumab plus prednisone were in sustained remission, as were 53.1% of those receiving tocilizumab every other week plus prednisone.
In contrast, only 14% of patients in the placebo plus short-course prednisone group had achieved sustained remission at that time (P<0.0001), Stone reported.
In addition, only 17.6% of patients receiving placebo plus long-course prednisone were in sustained remission at 1 year (P≤0.0002), he noted.
Giant cell arteritis involves inflammation of the medium and large arteries and is association with symptoms such as headache, visual difficulties, and constitutional symptoms. Inflammatory markers such as C-reactive protein (CRP) also typically are elevated.
The potential consequences include blindness, aortic aneurysms, and stroke. "This is a devastating disease and one that is difficult to study in clinical trials," Stone said. "For more than 65 years, there has been no new proven therapy," he added.
With steroid treatment, relapses are common with dose reduction and the majority of patients experience steroid-related toxicity. Attempts to use steroid-sparing agents including methotrexate and tumor necrosis factor inhibitors have largely failed.
Open-label studies have suggested a potential benefit to inhibition of interleukin-6 with agents such as tocilizumab, so Stone and colleagues conducted an international yearlong trial at 76 centers in 14 countries. Sustained remission at week 52 – meaning an absence of flare and normal CRP with adherence to the prescribed prednisone taper – was the primary endpoint.
Another important outcome was the cumulative steroid exposure, which was less than half in the tocilizumab groups than in the long-course prednisone group. In both of the tocilizumab groups, the cumulative median steroid dose was 1,862 mg, compared with 3,817 mg in the long-course prednisone group (P<0.0002). Tocilizumab had a powerful steroid-sparing effect, Stone noted.
Overall adverse events were similar across the four groups, with more than 90% of patients reporting any event. Serious adverse events were reported in 22% and 25.5% of the short-course and long-course prednisone groups, respectively, and in 15% and 14.3% of the weekly and every other week tocilizumab groups. A total of 12% and 9.8% of patients in the short-course and long-course prednisone groups withdrew from the study, as did 15% and 18.4% of patients in the weekly and every other week tocilizumab groups, respectively.
No patients died or experienced new vision loss during follow-up.
Primary Source
American College of Rheumatology
Stone J, et al "Efficacy and safety of tocilizumab in patients with giant cell arteritis: primary and secondary outcomes from a phase 3, randomized, double-blind, placebo-controlled trial" ACR 2016; Abstract 911.