In one study of 125 patients with GCA, adverse events associated with glucocorticoids were seen in 86% of patients, with two or more events occurring in 58%.2 The development of adverse glucocorticoid side effects was associated with age and higher cumulative glucocorticoid dose.
This is a concern because GCA is a disease of older people. The average age of onset for the disease is 72, and almost all people with the disease are older than 50.3
“Prednisone is effective, but associated with significant potential side effects, and it does not prevent relapses,” says Dr. Langford. “It has, therefore, been a high priority to identify effective therapeutic options that are safer than glucocorticoids to treat GCA.”
Potential to Reduce Relapses
In this randomized and blinded multicenter study, Dr. Langford and her colleagues set out to examine the efficacy and safety of abatacept combined with prednisone compared with prednisone alone for the treatment of GCA.1 The 49 patients enrolled in the clinical trial at 11 academic centers had newly diagnosed or relapsing GCA and were treated with abatacept 10 mg/kg intravenously on Days 1, 15 and 29 and at Week 8, together with prednisone administered daily according to a standardized dosage and tapering schedule. The 41 patients who were in remission at Week 12 were then randomized to continue abatacept or be switched to placebo IV once a month. Prednisone was stopped at Week 28.
At study completion, which was 12 months after the last patient was randomized, 10 patients treated with abatacept had relapsed and 10 stayed in remission, whereas 14 patients randomized to placebo had relapsed, and seven had stayed in remission. The relapse-free survival rate at 12 months was, therefore, 48% for those receiving abatacept and 31% for those receiving placebo (P=0.049). In addition, a longer median duration of remission was seen in those receiving abatacept compared with those receiving placebo (median duration 9.9 months vs. 3.9 months; P=0.023).
Side Effect Risk
Although assessing effectiveness was the primary endpoint of this study, it was not the only outcome that was examined. Dr. Langford says, “Although abatacept had low rate of toxicity in other disease settings, examining safety in GCA was a high priority in this trial.”
There was no difference in the frequency or severity of adverse events between the treatment arms of abatacept and placebo, including the rate of serious adverse events. Infection was of concern, and it was of note that there was no statistically significant difference in the frequency of infections between the two randomized groups.
Study Conclusions
Overall, “patients who achieved remission and were randomized to continue abatacept had a significantly higher rate of relapse-free survival compared with those who were randomized to placebo,” Dr. Langford says. “The difference between groups is clinically meaningful to patients with GCA and corresponds to a prolonged duration of remission, during which time they would not be exposed to glucocorticoids and their potential toxicities that impact quality of life.”
