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Tocilizumab plus prednisone bested prednisone alone in giant cell arteritis remission rates
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WASHINGTON — Tocilizumab plus a prednisone taper was associated with improved sustained remission rates compared with prednisone alone in a cohort of patients with giant cell arteritis, according to findings presented at the American College of Rheumatology Annual Meeting.
In a level 1 study, John H. Stone, MD, and colleagues aimed to assess tocilizumab for efficacy and safety in a cohort of 251 patients with giant cell arteritis (GCA). There were four treatment groups: 50 patients treated with short-course prednisone (26-week prednisone taper plus weekly subcutaneous placebo); 50 patients who received a long-course prednisone (52-week prednisone taper plus weekly subcutaneous placebo); 100 patients who received weekly subcutaneous tocilizumab 162 mg plus 26-week prednisone taper; and 50 patients who received every other week subcutaneous tocilizumab 162 mg plus 26-week prednisone taper. Patients were stratified by baseline prednisone dose (≤30 or >30 mg/day).
The primary outcome measure was the ratio of patients in sustained remission between week 12 and week 52. Specifically, investigators aimed to compare the tocilizumab groups with the short-course and long-course prednisone groups. Researchers defined sustained remission as the absence of flare and normalization of C-reactive protein (CRP) after week 12 combined with adherence to the protocol-defined prednisone taper.
Results indicated 56% of patients in the weekly tocilizumab group and 53.1% of those in the every-other-week group experienced sustained remission at 12 months, while 14% of those in the short-course prednisone group experienced this outcome. The other comparison demonstrated 17.6% of patients in the long-course prednisone group reached sustained remission.
“I strongly suspect that 56% is an underestimate of the true effect of tocilizumab in this setting,” Stone said. “This was highly statistically significant for the primary outcome and the secondary outcome.”
Stone noted there is a clear differentiation in time to flare between the treatment groups.
“The weekly tocilizumab group sustained its response,” he said. “The every-other-week tocilizumab group showed a bit of a drop-off after prednisone cessation.”
Elevated CRP levels were added to traditional ACR criteria, along with unequivocal symptoms of PMR and imaging evidence of large-vessel vasculitis. The inclusion of CRP in the analysis did not impact the primary endpoint, according to Stone.
Patients in both tocilizumab groups had less than half the median cumulative steroid exposure rates than those treated with long-course prednisone. All regimens yielded similar adverse event rates. Stone reported no fatalities, new vision loss or bowel perforations.
He concluded there are three new facts in giant cell arteritis.
“First, there is something new in GCA,” he said. “Second, tocilizumab has a powerful steroid-sparing effect in GCA. Third, the era of unending glucocorticoid treatment with no viable alternative is over.” – by Rob Volansky
Reference:
Stone JH, et al. Abstract #911. Presented at: The American College of Rheumatology Annual Meeting; Nov. 11-16, 2016. Washington.
Disclosure: Stone reports associations with Roche Pharmaceuticals.
Perspective
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Leonard Calabrese, DO
For me, the American College of Rheumatology Annual Meeting this year was a treat because it was the year for vasculitis. There were multiple plenary presentations on the field of vasculitis and I think we have broken through the ceiling. There is nothing more dramatic than the breakthrough of tocilizumab – interleukin-6 inhibition in the treatment of giant cell arteritis. The trial, with John H. Stone, MD, as the principal investigator and done on a multicentric basis, was extraordinarily impressive. It met all endpoints to robust degrees of statistical significance.
What did they show? They showed tocilizumab could control giant cell arteritis with minimal doses of steroids and the relapse rate was dramatically less with less glucocorticoids in patients with this difficult-to-manage disease. I expect to see fast-track approval for this drug in the near future. However, having said that, there are many questions that remain. What will be the dose? Will it be 8 mg? Will it be 4 mg per kilogram? The data was not clear to me of superiority. Secondly, what about toxicity? This was about a 250-some patient population study and it looked safe, but as the denominator grows with an elderly and vulnerable population, I do have concerns. Lastly, how will we use it? Does everybody get it? Do only people who are steroid failures get it? It will not be clear for a while and we will have to wait for regulatory approval.
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