Efficacy of Abatacept for Treating Vasculitis

Article

Two new studies find that abatacept plus prednisone improves duration of remission for giant cell arteritis patients, but not for Takayasu’s arteritis patients.

Two new studies find that abatacept plus prednisone improves duration of remission for giant cell arteritis patients, but not for Takayasu’s arteritis patients, compared with placebo. Giant cell arteritis is the most common form of vasculitis, while Takayasu’s arteritis is a rare form of vasculitis.

The studies were conducted in parallel by the same research team. The giant cell arteritis study appears in the March 3 online issue of Arthritis & Rheumatology while the Takayasu’s arteritis study appears in the March 8 online issue.

With giant cell arteritis and Takayasu’s arteritis, activated T cells play a critical role in disease pathogenesis. Abatacept works by blocking T cell activation. The Food and Drug Administration approved abatacept for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Prior studies have shown that abatacept has a low rate of toxicity, with its main side effects being infections and hypersensitivity.

Led by Carol Langford, M.D., of the Cleveland Clinic in the United States, both studies were conducted at 11 academic medical centers. Patients in both studies were enrolled and treated with abatacept 10 mg/kg IV on days 1, 15, 29, and week 8, along with prednisone. After 12 weeks, patients underwent a blinded 1:1 randomization to abatacept or placebo, with all patients undergoing a standardized prednisone taper so that the glucocorticoid was discontinued at week 28. Patients kept their randomized assignment until they met criteria for termination or 12 weeks after enrollment of the last patient. The primary end point was duration of remission or relapse-free survival. The secondary endpoint was toxicity.

In the first trial, 41 newly diagnosed or relapsing giant cell arteritis patients were evaluated. At 12 months, the relapse-free survival at was 48% for those receiving abatacept and 31% for those receiving placebo (p=0.049). A longer median duration of remission was observed for patients who received abatacept compared to patients who received placebo (9.9 months vs. 3.9 months, respectively; p=0.023). No difference was observed between the treatment arms for adverse events.

Giant cell arteritis is a chronic granulomatous vasculitic disease that that affects medium and large-sized arteries. The condition is more common in people over the age of 50. Glucocorticoids have been the foundation therapy for giant cell arteritis; however, glucocorticoids have been associated with high toxicity. Additionally, relapse occurs in at least 70% of patients.

“This study demonstrated that treatment of GCA with abatacept combined with glucocorticoids results in a longer duration of relapse-free survival than treatment with prednisone alone and is well tolerated,” wrote Langford and colleagues. “In the older patient population impacted by GCA, this potential for a glucocorticoid-sparing option is clinically important and meaningful.”

In the second trial, 26 newly diagnosed or relapsing patients with Takayasu’s arteritis were evaluated. At 12 months, the relapse-free survival was 22% for patients who received abatacept and 40% for patients who received placebo (p= 0.853). Patients treated with abatacept did not have a longer median duration of remission compared with placebo (5.5 months vs. 5.7 months, respectively). Additionally, there was no difference in adverse events by treatment arm.

“This was the first-ever randomized trial to be performed in TAK and in conducting this study, a great deal was learned about the challenges of performing a sufficiently powered trial in this disease,” wrote Langford and the study team.

Takayasu’s arteritis is a vasculitic disease that commonly affects the aorta, its major branches, and the pulmonary arteries. The disease is predominantly diagnosed in women and is most common in people between the ages of 18-40. In the United States, the estimated incidence of Takayasu’s arteritis is 2.6 cases per million per year. Damage from Takayasu’s arteritis can result in vascular stenoses or aneurysms.

Glucocorticoids are the main therapy for Takayasu’s arteritis; however, only 28-50% of patients achieve remission with this treatment. Safer, more effective therapies are needed to better manage Takayasu’s arteritis patients.

In summary, both studies raise interesting questions about the best strategies for treating vasculitis. To date, it is not clear whether giant cell arteritis and Takayasu’s arteritis should be considered unique diseases or if they represent a part of a single clinical spectrum. 

“The divergence in therapeutic efficacy seen in these parallel trials provides strong evidence of the need to continue scientific investigations to better understand the underlying immunologic nature of these diseases, which in turn may guide therapeutic strategies,” wrote Langford and colleagues. 

 

Disclosures:

The National Institute of Arthritis and Musculoskeletal and Skin Diseases in the United States funded this research.

References:

Carol A. Langford, David Cuthbertson, Steven R. Ytterberg, et al. “A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis,”Arthritis & Rheumatology. Published online March 3, 2017. DOI: 10.1002/art.40044

Carol A. Langford, David Cuthbertson, Steven R. Ytterberg, et al. “A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis,”Arthritis & Rheumatology. Published online March 8, 2017. DOI: 10.1002/art.40037

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