Results from a phase III study provide ‘positive news for patients with GCA’ says A/Prof Tony Sammel.
A trial of upadacitinib for giant cell arteritis resulted in almost half of the patients achieving sustained remission, according to findings presented in a press release.
The phase III SELECT-GCA study was conducted in numerous centres, including several in Australia. A total of 46% of patients given 15mg upadacitinib plus a steroid taper achieved sustained remission, compared with 29% of patients given placebo and steroid taper.
“This is positive news for patients with GCA,” said Associate Professor Anthony Sammel, who was involved with the trial at its Prince of Wales Hospital site in Sydney.
“At the moment, the standard of care is tocilizumab with a 26-week prednisone taper. We now have a second agent which has been shown to have efficacy in a phase III trial.”
“At this stage, in whom we use it and how we use it is still to be determined.”
The trial included 428 patients randomised to receive 15mg upadacitinib in combination with a 26-week corticosteroid tapering regimen, 7.5mg upadacitinib in combination with a 26-week corticosteroid tapering regimen or placebo with a 52-week steroid taper.
The primary endpoint was sustained remission from week 12 through week 52, defined as an absence of GCA symptoms and adherence to the steroid taper.
The difference in the proportion of patients meeting the primary endpoint – 46% vs 29% for the 15mg group vs placebo respectively – was statistically significant.
The rates of complete remission, which included lack of symptoms, taper adherence and normalisation of both erythrocyte sedimentation rate and high sensitivity C-reactive protein from week 12 through 56, were significantly higher for the 15mg upadacitinib group than placebo (37% vs 16% respectively). There were also significantly fewer flares in the 15mg upadacitinib group than placebo (34% vs 56%).
The press release noted that the results for the 7.5mg group did not meet the primary or any secondary endpoints but the figures weren’t reported.
The safety profile for upadacitinib was consistent with that observed in approved indications with no new safety signals.
“Clearly, it’s been shown to be effective, although it’s not a panacea – we’re still seeing a third of patients flaring,” said Professor Sammel.
He noted that the findings are similar to, and perhaps numerically less impressive than those for tocilizumab in the GiACTA trial, which reported sustained remission of 53% and a flare rate of 23%, but acknowledged you can’t compare directly between trials.
“The issues with tocilizumab really relate to the fact that the PBS only provides 12 months of supply, and when we stop the medicine at 12 months, we see a relapse rate of 50 to 60% in the subsequent two years.
“So it’s a very useful agent when you’re on it, but there are issues with how long to continue it and issues with relapse when it’s stopped. Some patients are intolerant of it, they get cytopenias or they have infections, or they have other reasons that they’re unable to do it – it’s an injection, obviously, which is difficult for some patients.”
However, he pointed out that there are also issues with JAK inhibitors, in particular the increased risk of cardiovascular events and malignancies that emerged in the ORAL Surveillance trial, particularly for people older than 65 with cardiovascular risk factors.
“I think that’s an issue in the GCA cohort, where the median age is 73, so there are going to be patients where ideally we wouldn’t use a JAK inhibitor first line,” said Professor Sammel.
“However, there’s probably that younger cohort of patients in their 50s who don’t have cardiovascular risk factors where it’s going to be possibly quite a useful agent. And I think it’s going to be a useful agent in people who either have relapsed through tocilizumab, or are unable to tolerate it due to cytopenias, or have a reason why they don’t want to use an injection medication.”
The second stage of the study will evaluate the safety and efficacy of continuing versus withdrawing upadacitinib in maintaining remission in participants who achieved sustained remission in the first period, which Professor Sammel said could favour the use of upadacitinib over tocilizumab.
“We’re going to see if you can maintain that remission state when you come off the drug, because relapse is one of the big problems with tocilizumab. That’s something of potential benefit, depending on what the data ends up looking like,” he said.
AbbVie noted in its press release that the results will be presented at “a future medical meeting”.
