Combined tocilizumab and prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo in sustaining glucocortoid-free remission in patients with giant-cell arteritis, according to study results published in the New England Journal of Medicine.
Previous studies on tocilizumab, a monoclonal antibody that targets the receptor for the inflammatory cytokine IL-6, indicated that intravenous tocilizumab allowed for a diminution in the steroid dose amounts required for symptom reduction. The US Food and Drug Administration (FDA) approved subcutaneous administration of the drug for treatment of several forms of arthritis, including giant cell arteritis.
John Stone, MD, MPH, of the Massachusetts General Hospital (MGH) rheumatology unit, and colleagues conducted a subsequent 52-week GiACTA trial, the largest ever conducted in giant cell arteritis. They enrolled 251 patients at 76 sites in Europe and the United States, and randomly assigned participants to 4 groups: 100 received weekly tocilizumab injections along with prednisone injections that were tapered over 26 weeks; 50 received tocilizumab every other week, with a 26-week tapered prednisone dose; 50 received weekly placebo injections, with 26-week tapered prednisone doses; and 51 received weekly placebo injections with prednisone tapered over 52 weeks. All participants received a weekly or biweekly injections of either tocilizumab or placebo throughout the year-long study period.
Members of the tocilizumab groups received total prednisone doses averaging 1862 mg, while the placebo/26-week prednisone group averaged 3296 mg and the placebo/52-week prednisone group averaged 3838 mg.
A total of 56% of patients in the tocilizumab-weekly group and 53% of patients in the tocilizumab-every-other week group had sustained remission at 52 weeks (the primary outcome), compared with 14% of the patients in the placebo group who underwent the 26-week taper
(P <.001 for tocilizumab group with placebo) and 18% of patients in the placebo group who underwent the 52-week taper (P <.001 for tocilizumab group with placebo).
Serious adverse events were more likely in the placebo/prednisone groups, probably attributable to the higher cumulative prednisone doses, and participants receiving tocilizumab experienced consistent and significant improvements in their quality of life.
“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,” the researchers said. “Tocilizumab treatment was associated with a reduction in the cumulative prednisone dose over the 52-week trial period. Although both the regimen of weekly tocilizumab and the regimen of every-other-week tocilizumab were superior to the 26-week and 52-week prednisone-plus-placebo regimens with regard to sustained remission, weekly treatment with tocilizumab resulted in greater disease control than did treatment with tocilizumab every other week.
“A 2-year, open-label, follow-up phase of this trial may provide additional information pertaining to the safety and efficacy of tocilizumab beyond 52 weeks,” the researchers concluded.
Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377:317-328. doi:10.1056/NEJMoa1613849