Prednisone tapering fails in most patients with giant cell arteritis
CHICAGO — The majority of patients with giant cell arteritis who are treated with prednisone are unsuccessful in tapering the drug, unless combined with tocilizumab, and more than 80% of disease-related flares occur while prednisone is still in use, according to data presented at the 2019 Interdisciplinary Autoimmune Summit.
“How often does prednisone fail? This is a remarkable question that we, four years ago, did not know the answer to,” John H. Stone, MD, director of clinical immunology at Massachusetts General, told attendees. “This, despite the fact that we have had glucocorticoids as the standard of care treatment for giant cell arteritis, as a corner stone of so many of our other inflammatory diseases. For 70 years, we didn’t know the answer to this question.”
According to Stone, this changed when he and his team in 2017 published the results of the GiACTA study in the New England Journal of Medicine. During the trial, 50 patients were treated with prednisone taper plus a placebo for 26 weeks, and another 50 patients were treated with the same regimen for 52 weeks. In addition, 100 patients received 26 weeks of prednisone taper plus 162-mg doses of tocilizumab (Actemra, Genentech) once per week, and 50 patients were treated with the same duration of prednisone taper, but with the tocilizumab administered every two weeks.
The primary outcome was the rate of sustained prednisone-free remission at week 52 in each tocilizumab group, compared with the rate in the placebo group treated with the 26-week prednisone taper. The secondary outcome was the rate of remission in each tocilizumab group, compared with the placebo group treated with the 52-week prednisone taper.
“So, how often does prednisone fail? This trial finally gave us the answer to that question, after 70 years,” Stone said. “‘Frequently,’ is the answer.”
More specifically, in the 26-week prednisone-only group, only 14% of patients achieved the primary outcome. Among those treated with prednisone only for 52 weeks, just 17.6% achieved the primary outcome.
“That is an astonishingly high failure rate,” Stone noted. “I think the reason we didn’t all appreciate it, and didn’t know it would be that high, is because, in practice, we haven’t taken patients off of prednisone — we just let them stay on 5 to 10 mg per day, or more.”
In addition, Stone said the more than 80% of giant cell arteritis flares occur when the patient is still being treated with prednisone, and that, in 60% of cases, they occur when the patient is receiving more than 5 mg per day.
As well as being superior to prednisone as monotherapy, tocilizumab was also safer, Stone added. According to the study, serious adverse events occurred in 15% of patients in the group treated with weekly tocilizumab, 14% in those who received tocilizumab every other week, 22% in patients in the 26-week prednisone group, and 25% in patients treated with the 52-week prednisone taper.
Regarding when to cease tocilizumab, Stone said additional research will be coming soon, but noted that he had allowed one of his patients to stop after one year; two years later, the patient remains in remission, he said.
“Tocilizumab induces steroid-free sustained remissions, is safer than treatment with prednisone alone and, in some patients, may be discontinued safely after one year,” Stone said. “More data will be presented on this at EULAR.” – by Jason Laday
Stone JH. Breaking Down Barriers to the Optimal Management of Giant Cell Arteritis. Presented at: Interdisciplinary Autoimmune Summit; April 5-7, 2019; Chicago.
Disclosure: Stone repots consulting fees and research grants from Genentech and Roche.