Half of GCA patients receiving tocilizumab remained in remission 2 years after withdrawal

ATLANTA — Approximately 47% of patients in clinical remission after receiving 1 year of weekly tocilizumab for giant cell arteritis maintained their treatment-free remission for an additional 2 years, according to a speaker at the 2019 ACR/ARP Annual Meeting.

“Tocilizumab was demonstrated in a randomized, double-blind, placebo-controlled published two years ago to be superior to prednisone for achieving sustained remission at one year,” John H. Stone, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, told Healio Rheumatology. “The results of that trial, which was part one of the GiACTA trial led to the approval by regulatory agencies in the United States and across the world for tocilizumab for giant cell arteritis.”

“A very important question, however, was addressed in this part two of the trial,” he added. “Among patients who were treated with weekly tocilizumab, and did well in part one, then what would happen when tocilizumab was stopped?”

To determine the long-term maintenance of efficacy and safety of tocilizumab (Actemra, Genentech) in patients with giant cell arteritis, Stone and colleagues conducted a 2-year extension of their previous phase 3, 52-week GiACTA trial. After the trial’s double-blind period, patients who achieved clinical remission were instructed to cease tocilizumab treatment. A total of 215 participants entered this extension. The researchers defined clinical remission as the absence of flare per investigator assessment without the need for normalizing C-reactive protein levels of less than 1 mg/dL.

Treatment for giant cell arteritis, in the form of starting or ceasing open-label tocilizumab or glucocorticoids, was left to the investigator’s discretion based on patients’ disease status. Outcomes included clinical remission with no flares maintained throughout part two, flare, time to first flare, treatments received, cumulative glucocorticoid dose and safety. Among the patients who entered part two of the trial, 197 completed all 3 years, including the initial one year of treatment in part one.

According to the researchers, among the 81 patients who received weekly tocilizumab and achieved clinical remission at week 52 of part one of the trial, 47% maintained their remission during part two. Among the 36 participants treated with tocilizumab every other week and achieved remission during part one, 36% maintained their remission status. In addition, of the 51 patients originally treated with tocilizumab who maintained remission in part two, 65% were treatment-free, compared to 45% of patients who received placebo in part one who maintained remission in part two.

The median time to first flare was 575 days for patients who received weekly tocilizumab in part one and 428 days for those previously treated every other week. Among those in the placebo groups in part one, the median time to first flare was 162 days for those who received placebo plus 26 days of prednisone tapering and 295 days for those treated with placebo plus 52 days of prednisone tapering. Among patients who received tocilizumab and achieved remission in but one, but who experienced flares in part two, retreatment with tocilizumab, either with or without glucocorticoids, was effective for restoring clinical remission.

In addition, cumulative glucocorticoid dose over the 3 years total study period was lowest among patients who received weekly tocilizumab in part one, at 2,647 mg per day, compared with 3,782 mg for those treated with tocilizumab every other week, 5,248 mg for those who received a placebo plus 26-week prednisone tapering and 5,323 mg for those treated with placebo plus 52 weeks of prednisone tapering.

Serious adverse events rates during all 3 years of parts one and two were 23.2 per 100 patient-years for patients who never received tocilizumab, and 25.4 for patients who received at least one dose of tocilizumab. Serious infection rates were 4.6 per 100 patient-years for patients who never received tocilizumab, and 3.5 for those treated with at least one dose.

“The implications of this, I think, are very clear,” Stone said. “As soon as possible, patients who are diagnosed with giant cell arteritis, or who have a flare of giant cell arteritis having been previously diagnosed, should be started on IL-6 receptor blockade as soon as possible. They should also be started on prednisone, and that prednisone should be tapered as quickly as possible.”

“However, the main point is that IL-6 receptor blockade should be as soon as it can be approved,” he added. “It will lead to a higher likelihood of sustained remission over the first year, less cumulative prednisone, and then a significant number of those patients will be able to stop therapy and be on no treatment for a significant period of time — at least two years.” – by Jason Laday

Reference:
Stone J. Long-term outcome of tocilizumab for patient with giant cell arteritis: Results from part 2 of a randomized controlled phase 3 trial. Presented at: American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; Nov. 9-13, 2019; Atlanta.

Disclosure: Stone reports professional relationships with Genentech, Roche and Xencor. Please see the abstract for all other authors’ relevant financial disclosures.