Tocilizumab's Efficacy in Treating Giant Cell Arteritis

A randomized clinical trial of tocilizumab to treat giant cell arteritis finds that the drug given in combination with a glucocorticoid is more effective than a glucocorticoid and a placebo.

Giant cell arteritis causes the inflammation of the arterial lining in medium and large arteries. Accompanied by symptoms such as headache and fatigue, giant cell arteritis can cause stroke or reduced blood flow to the eye, which can in turn result in vision loss.

Glucocorticoids are the gold-standard treatment for this disorder, but they come with a high risk of side effects and mortality, researchers Peter Villiger, M.D., and Sabine Adler, M.D., of the University Hospital of Bern in Switzerland and their colleagues reported March 4 in The Lancet. The researchers sought to investigate an alternative treatment in the monoclonal antibody tocilizumab. 

With funding from Roche and the University of Bern, the researchers recruited 30 patients 50 years of age and older with new or recurrent giant cell arteritis. They randomly assigned 20 patients to receive treatment with tocilizumab plus prednisolone, and 10 to receive prednisolone and a placebo. [[{"type":"media","view_mode":"media_crop","fid":"46927","attributes":{"alt":"©AlilaMedicalMedia/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_4092332114215","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5487","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©AlilaMedicalMedia/Shutterstock.com","typeof":"foaf:Image"}}]]

By week twelve of the study, 85 percent of tocilizumab patients (17) achieved remission, compared with 40 percent of patients in the placebo group (4). The risk difference between groups was 45 percent (CI: 95 percent, 11-79, p=0.0301).

Eighty-five percent of tocilizumab patients also achieved relapse-free survival by week 52 of the trial, the researchers reported, compared with 20 percent (2) in the placebo group. Half of the placebo group and 35 percent of the tocilizumab group experienced serious adverse events.

Patients in the tocilizumab group were more likely to taper prednisolone to zero by the end of the trial (80 percent versus 20 percent in the placebo group), and the tocilizumab group stopped glucocorticoids 12 weeks earlier, on average, than the placebo group (CI: 95 percent, 7-17, p<0.0001). As a result, the cumulative prednisolone dose after 52 weeks in the tocilizumab group was 43 mg/kg, compared with 110 mg/kg in the placebo group (p=0.0005), the researchers wrote.

"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," they concluded.

Because tocilizumab targets interleukin-6 receptors, the trial suggests the IL-6 plays a key role in giant cell arteritis. Previous research had already found that IL-6 is increased in the serum of giant cell arteritis patients.  

References:

Villiger PM, Adler S, Kuchen S, et al. “Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomized, double-blind, placebo-controlled trial.” The Lancet 2016. DOI: http://dx.doi.org/10.1016/S0140-6736(16)00560-2

Emilie D, Liozon E, Crevon M-C, et al. “Production of interleukin 6 by granulomas of giant cell arteritis.” Human Immunology 1994;39(1):17–24. doi:10.1016/0198-8859(94)90096-5.