Trial Data Reveals the Limitations of Steroids in Giant Cell Arteritis Therapy

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AMSTERDAM—Just how seldom prednisone is successful at inducing remission in giant cell arteritis (GCA), despite such a long history of use for the disease, is one of the many lessons to emerge from the data in the GiACTA trial, said the principal investigator of the trial, which is the largest ever in GCA and is still ongoing in its assessment of how to best use the IL6-inhibitor tocilizumab for these patients.

Clinical Findings

The trial’s findings also offer lessons on the steroid load that GCA patients on prednisone are prescribed, on quality-of-life improvements to which GCA patients can reasonably aspire when taking tocilizumab and the best way forward in the treatment of these patients, John Stone, MD, MPH, professor of medicine at Harvard Medical School, Boston, and the principal investigator of the trial, said in a session at EULAR: the Annual European Congress of Rheumatology.

In the trial, 58 of the 101 patients who received prednisone without tocilizumab—half of them on a tapering dose over 26 weeks, and the other half tapered over a year—had disease flares within one year.¹

“This is really bad,” Dr. Stone said. “[Prednisone] has been the cornerstone therapy of our disease for seven decades, and 60% of patients flared within one year—many while they were still taking treatment.” Many of these patients were taking between 5 mg and 20 mg of prednisone a day. He added that clinicians didn’t have this information until the GiACTA trial was done.

The prednisone-only groups fared poorly in the trial’s primary outcome of disease remission at 52 weeks—only 14% of the 26-week taper group and 18% in the 52-week taper group achieved remission.

The routine failures of prednisone and the disease flares seen in just 24% of tocilizumab-treated patients over a year—with positive effects seen far earlier than a year—are reason to start treating GCA patients on tocilizumab and steroids right away, Dr. Stone said.

“If you put the patient on a full year of steroids, the patient will only have a third of a chance of being off prednisone completely at one year,” Dr. Stone said, noting that there’s greater than an 80% chance of failure over one year. “I think it’s better to start right off with tocilizumab and steroids.”

Patients in the prednisone groups of GiACTA ended up getting the same cumulative dose of the drug, whether they were on a 26-week taper or a 52-week taper, because those in the 26-week arm flared earlier, requiring a boost in prednisone use.

The data from the trial also highlight the deficiencies of sedimentation rate and C-reactive protein (CRP) in assessing disease activity, Dr. Stone said. A third of the flares across both prednisone groups happened in those with a normal CRP.

“We tend to use these acute phase reactant measurements as a crutch, and I think these data underscore very pointedly how bad a crutch that is to use,” he said.

This reinforces the idea that GCA, and GCA flares, are clinical diagnoses.

“We will continue to look for the optimal imaging study and approach to diagnosing disease flare,” he said. “But for quite a while to come, I am sure clinical judgment is going to remain very important in taking care of patients with this disease.”

‘I would really aim to get patients off steroids completely in four months or so.’ —Dr. Stone

Quality of Life

Another striking finding from the trial was in the quality-of-life data. Improvements among patients receiving tocilizumab brought their quality-of-life measurements to levels that surpassed normative values for age- and gender-matched patients.

“I’ve never seen quality-of-life data like these,” Dr. Stone said. He mentioned these surprising improvements may have to do with the role IL-6 seems to play in depression.

Patients in the tocilizumab groups were also less likely to have serious adverse events.

Long-Term Results

As he discussed messages to be gleaned from the GIACTA data, Dr. Stone discussed the patient whose progress on tocilizumab prompted the trial. The 58-year-old man was started on prednisone, with a plan to taper over six months. He flared when the prednisone was stopped. Then he was started on tocilizumab.

At one year, Dr. Stone chose to stop the drug. “He was feeling great. He had been off prednisone for many months. He said, ‘Do I really have to continue to inject this stuff every week?’ I said, ‘Well, we should stop it and see what happens.’” His CRP and ESR are measured every month or two, and have remained low. He’s been in remission for a year since stopping tocilizumab.

Many questions remain for managing GCA patients on tocilizumab. For one thing, how should their disease activity be assessed over time?

“I think we overuse imaging in these patients,” Dr. Stone said. “I think the key will be understanding how he is feeling. His clinical symptomatology and his acute phase reactants, which are simple and easy to measure, will also be crucial.”

And how quickly can prednisone be stopped?

“I think even six months is too long a course in many of our patients,” Dr. Stone said. “This needs to be studied in other trials and longitudinal series. But I would really aim to get patients off steroids completely in four months or so.”

Thomas R. Collins is a freelance writer living in South Florida.

References

1. Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017 Jul 27;377(4):317–328.