Moving away from ‘failed’ prednisone to IL-6 blockade in giant cell arteritis
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Recent landmark study results have shown that interleukin-6 blockade may be superior to prolonged prednisone therapy in giant cell arteritis, according to a presenter at the 2020 Congress of Clinical Rheumatology-West.
“The great majority of patients with GCA are unsuccessful in tapering their prednisone,” John H. Stone, MD, director of clinical rheumatology at Massachusetts General Hospital, said in his presentation. “We did not know how often they failed until the GIACTA trial.”
Stone framed the discussion by presenting case patient data and zeroing in on questions pertaining to the efficacy and safety of prednisone compared with those reported for IL-6 inhibition with tocilizumab (Actemra, Genentech).
One of the patients Stone discussed had undergone months of prednisone therapy for GCA but who nonetheless was admitted to the ED with a widened mediastinum. He was bloated and had gained significant weight in what Stone described as “a very scary situation.”
This admission was in 2010, “when there was nothing else for GCA,” according to Stone. “Clearly, he had failed on steroids.”
Stone described this as a “perfect opportunity” to address two key questions: one was the frequency with which steroids fail, and the other was whether IL-6 inhibition could be a viable treatment option.
The patient in the ED underwent intravenous treatment with tocilizumab. “On day 3 it looked like tocilizumab had been a big dud,” Stone said, reporting no change in the patient’s acute phase reactants.
But, ultimately, the patient’s CRP and ESR began to fall and serum IL-6 concentration “soared,” according to Stone. “This seemed to confirm everything that we thought we knew about IL-6 physiology and IL-6 blockade,” he said. “This all led directly to the GIACTA trial, which aimed to answer how often prednisone fails.”
The answer, according to Stone, is “often,” as high as 80%. Moreover, findings from GIACTA showed that tocilizumab not only improved disease parameters, but also quality of life. “I have never seen a biologic agent perform that well in any disease,” he said.
While the full results from GIACTA are still forthcoming, Stone offered clinicians some concrete advice on balancing prednisone with tocilizumab in GCA. “Patients want to know, what are my chances of treatment success with prednisone, of being in remission and off prednisone at 1 year?” he said.
Given the high rate of flares, along with the inherent adverse events associated with prednisone in mind, Stone offered a straightforward response to this question: “I always start IL-6 receptor blockade as soon as I can,” he said.
The final component of Stone’s presentation dealt with tocilizumab tapering. He reported that findings from GIACTA showed that 42% of patients who underwent IL-6 blockade maintained remission for 2 years “without requiring a milligram of prednisone or retreatment with tocilizumab.”
That said, Stone acknowledged some patients will require ongoing, if not lifetime, treatment with tocilizumab, which he reported can be “unappealing.” But he believes this is a worthwhile tradeoff, given that the drug can reduce flares, induce remission and be safely tapered.
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Stone JH. Current Recommendations in Treatment of Vasculitis. Presented at: Congress of Clinical Rheumatology-West annual symposium; October 8-11, 2020 (virtual meeting).
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