Treatment with abatacept plus a prednisone taper significantly reduced the rate of relapse and improved duration of remission compared with placebo in patients with giant cell arteritis (GCA) who achieved remission with abatacept plus prednisone. Moreover, the addition of abatacept to standard treatment with prednisone did not increase toxicity compared with prednisone alone (Langford CA, et al. Arthritis Rheumatol. 2017;69: 837-845).
At 12 months, the rate of relapse-free survival was 48% for those treated with abatacept and 31% for those who received placebo, representing an absolute difference of 17% favoring abatacept (P = .049). Median duration of remission was 9.9 months for abatacept versus 3.9 months for placebo (P = .023).
“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, providing supportive evidence of the efficacy of abatacept in this study population. This difference between groups is clinically meaningful to patients with GCA; corresponding to a prolonged duration of remission during which time they are not exposed to glucocorticoids and their potential toxicities that impact quality of life. These findings are particularly impactful given the older patient population affected by this disease, which is the most common form of primary systemic vasculitis,” reported lead investigator Carol A. Langford, MD, MHS, FACP, Chair, Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, OH, and colleagues.
GCA is characterized by vasculitis of unknown cause that typically attacks medium- and large-sized arteries, including the carotid arteries, aorta, and major branches. The disease mainly affects people aged >50 years, and is the most common type of systemic vasculitis in North America. Although glucocorticoids are effective in improving GCA symptoms and preventing cranial ischemic complications such as blindness, these drugs have significant toxicity, especially in older patients. More than 70% of patients with GCA will relapse and require long-term glucocorticoid therapy.
“It has therefore been a high priority and unmet need in GCA to identify safer, effective therapeutic options beyond glucocorticoids,” the study investigators noted.
Abatacept, FDA approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, inhibits T-cell activation, which is thought to play a critical role in the pathogenesis of GCA. Abatacept has a low rate of toxicity, and the most common adverse events associated with use of the drug are hypersensitivity and infection. These observations formed the rationale for studying abatacept in GCA.Study Details
The multicenter study enrolled 49 patients at 11 academic centers with newly diagnosed or relapsed GCA with active disease in the last 2 months leading up to the trial. All patients were treated with intravenous infusions of abatacept 10 mg/kg on days 1, 15, and 29, and on week 8, along with prednisone. At week 12, 41 patients in remission were randomized in a double-blind fashion to continue receiving abatacept every 4 weeks thereafter (n = 20) or to switch to placebo (n = 21). At randomization, all patients were receiving prednisone 20 mg daily with standardized tapering continuing after randomization, and discontinued at week 28.
The need for an increased prednisone dose or to restart prednisone was considered a relapse criterion. Patients continued receiving abatacept or placebo until they met criteria for early termination, or until 12 months after enrollment of the last patient.
Patients whose disease relapsed discontinued the study drug and were treated in accordance with best medical judgment. After discontinuing the study drug, patients were scheduled for posttreatment visits at weeks 4, 12, and 24, and then they were classified as being off of the study.
Imaging of the aorta and branches was conducted at study entry, and was repeated every 6 months in those with identified large-vessel involvement.
The primary end point was remission duration (ie, relapse-free survival), and the secondary end point was toxicity.Safety
“In seeking to identify a less toxic treatment option in GCA, the safety of abatacept was an important aspect of this study,” reported Dr Langford and colleagues.
No difference was found in type or severity of adverse events in patients randomized to receive abatacept compared with those who received placebo. In addition, no enhanced signal of toxicity was observed during the first 12 weeks of the trial, when all patients concurrently received high-dose glucocorticoids plus abatacept.
Strengths of the study include the use of clinical investigators experienced with the care of patients with GCA, and with the double-blind, randomized, withdrawal trial design. Study limitations cited by Dr Langford and coinvestigators include the small size of the study and the lack of biomarkers for disease activity, remission, and relapse. Despite these limitations, the investigators believe that the difference in relapse-free survival favoring abatacept was clinically meaningful.
Dr Langford and colleagues cautioned that because abatacept was used as an adjunctive treatment with standardized prednisone in this study, no conclusions can be reached regarding use of abatacept for the treatment of GCA independent of glucocorticoids.
Other novel drugs should continue to be studied in GCA, they added.