22 June 2020

Three-year GiACTA trial results revealed

Rheumatology

The optimal regimen of tocilizumab for giant cell arteritis is weekly, not fortnightly, the long-awaited, three-year GiACTA trial results show.

Presenting the results in a virtual talk at EULAR this year, Harvard University rheumatologist Professor John Stone said weekly tocilizumab treatment for a year delayed the time to flare and resulted in lower steroid exposure in patients with either new-onset or relapsing GCA compared with placebo – and that these differences were sustained throughout the two year follow up.

“Weekly tocilizumab dosing was consistently better than every-other-week dosing,” he said. “These results support the early use of tocilizumab in GCA and support weekly tocilizumab as opposed to every other week regardless of the type of GCA.”

In the first year of the GiACTA trial, around 250 patients with GCA were randomised to receive either tocilizumab weekly, tocilizumab every other week or a placebo – as well as a prednisone taper for all patients in the trial.

In the second year of the trial, the randomised treatment regimen was halted, and patients moved over to an open-label treatment phase where their doctor prescribed tocilizumab or glucocorticoids (or both) at their discretion.

The third year of the trial tracked how the initial 12-month tocilizumab treatment affected time to flare and total steroid dose.

The results showed that weekly tocilizumab was superior to fortnightly tocilizumab and placebo in terms of extending the time to first flare and reducing the total amount of steroids needed.

Just under half of patients who were assigned to receive tocilizumab every week remained flare-free during the three-year trial (new-onset, 49%; relapsing, 47%), but this was a higher proportion of patients than in the placebo group (new-onset, 28%; relapsing, 31%) and the tocilizumab fortnightly group (new-onset, 27%; relapsing, 35%).

Weekly tocilizumab over 52 weeks for patients with GCA has been PBS subsidised for about a year now, so the GiACTA trial results were “clinically extremely relevant” for Australian patients, Professor Stephen Hall, a rheumatologist at Cabrini Medical Centre in Melbourne and the director of Emeritus Research, said.

“They tell us that even if you take tocilizumab for the full 12 months, the majority of people will relapse,” he said. “It gives us a better idea of what we tell our patients will be achieved by the 12 months of tocilizumab.

“The trial also discourages us from using only every other week tocilizumab because it didn’t achieve the goals that we were hoping to achieve over the longer term,” Professor Hall said.

“It seemed to achieve the 12 months, but when you follow them out longer, it didn’t really fulfil that promise. So, the three-year data has been useful for getting a better definition of what the optimal dose of tocilizumab is.”

Patients with GCA in Australia are only eligible for PBS-subsidised tocilizumab if they have been diagnosed through biopsy or if there is evidence of large?vessel vasculitis by MR angiography, CT angiography or PET/CT; diagnosis through ultrasound is insufficient.

“So, there are a number of ways we can diagnose GCA,” said Professor Hall. “We can diagnose it by biopsy the artery. We can diagnose it by doing advanced imaging like a PET scan, or MR angiograms, or CT angiograms of the vessels, or we can do an ultrasound of the temporal arteries.

“Now, in the clinical trial of GiACTA, they didn’t use ultrasound mainly because it’s an American-driven trial and the Americans don’t use much ultrasound.”

PBAC drew on the GiACTA trial results to make its decision, and “decreed that ultrasound was not an acceptable documentation for GCA”.

The end result was that people who were diagnosed with GCA using ultrasound were unfortunately excluded from getting tocilizumab in Australia unless they underwent a further biopsy, Professor Hall said.

“We’ve got one year’s worth of treatment that we can get on PBS so long as they haven’t been diagnosed on ultrasound,” he said.

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