Adding tocilizumab to tapered glucocorticoid therapy in patients with giant-cell arteritis (GCA) led to higher rates of sustained remission at 52 weeks than placebo plus tapered glucocorticoid therapy, according to the results of the phase 3, randomized, double-blind, 52-week, placebo-controlled GiACTA (GCA Actemra) trial.1
GCA is a chronic inflammatory disorder that targets large- and medium-sized arteries. Symptoms of the disease include headaches; visual disturbances; polymyalgia rheumatica; claudication of the arms, legs, and jaw; and inflammation of the aorta and its branches. For years, the cornerstone of treatment for patients with GCA has been glucocorticoids, with the goal of alleviating headaches, suppressing inflammation, and preventing visual loss. However, because of the cumulative toxic nature of these medications,2 investigators have been searching for alternative therapies that can be used in the management of patients with GCA. One such drug is tocilizumab, a monoclonal antibody FDA approved for the treatment of patients with moderate-to-severe rheumatoid arthritis and juvenile idiopathic arthritis.3 In May 2017, the FDA expanded approval of subcutaneous tocilizumab for the treatment of adult patients with GCA.
This approval was based largely on data from the GiACTA trial (N = 251).1 In this study, John H. Stone, MD, MPH, Director, Clinical Rheumatology, Massachusetts General Hospital, Boston, and colleagues sought to evaluate whether adding subcutaneous tocilizumab to prednisone therapy in patients with GCA would result in higher rates of sustained disease remission than placebo.
Patients in GiACTA were randomized to 1 of 4 treatment arms, which included tocilizumab 162 mg weekly plus prednisone tapered over 26 weeks, tocilizumab 162 mg every 2 weeks plus prednisone tapered over 26 weeks, weekly placebo plus prednisone tapered over 26 weeks, and weekly placebo plus prednisone tapered over 52 weeks. The primary end point was the proportion of patients who achieved sustained glucocorticoid-free remission through 52 weeks.
At 52 weeks, 56% of patients in the weekly tocilizumab arm and 53% of patients in the cohort receiving tocilizumab every 2 weeks had sustained remissions compared with 14% of patients in the placebo arm who received a 26-week prednisone taper and 18% of patients in the placebo arm who received a 52-week prednisone taper.
“Tocilizumab combined with a 26-week prednisone taper was superior to either a 26-week or 52-week prednisone taper plus placebo with regard to the sustained remission of giant-cell arteritis,” Dr Stone and colleagues reported.
Serious adverse events occurred more frequently in patients who received placebo plus prednisone (22% in the 26-week prednisone taper arm and 25% in the 52-week prednisone taper arm) than in those who received tocilizumab plus prednisone (15% in the weekly tocilizumab arm and 14% in the cohort receiving tocilizumab every 2 weeks). The most frequently observed serious adverse event was infection.
Dr Stone and colleagues suggested that the higher rates of serious adverse events in the placebo arms may be associated with the high cumulative doses of prednisone given to these groups.
“Patients who were assigned to the placebo groups received approximately twice the cumulative glucocorticoid dose as patients assigned to the tocilizumab groups. The numerically higher rates of serious adverse events in the placebo groups might have been the result of the effects of glucocorticoids,” they said.
Although tocilizumab administered weekly or every 2 weeks yielded higher rates of sustained glucocorticoid-free remission in patients with GCA than placebo when used in combination with tapered prednisone, Dr Stone and colleagues asserted that further investigation will be necessary to determine the long-term safety and efficacy of tocilizumab in this patient population. They also noted that a 2-year, open-label follow-up to the GiACTA trial may be helpful in providing these additional data.
- Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017; 377:317-328.
- Fraser JA, Weyand CM, Newman NJ, Biousse V. The treatment of giant cell arteritis. Rev Neurol Dis. 2008;5:140-152.
- US Food and Drug Administration. FDA approves first drug to specifically treat giant cell arteritis. May 22, 2017. www.fda.gov/newsevents/newsroom/pressannouncements/ucm559791.htm. Accessed September 18, 2017.