By Leonard Calabrese, DO and  Rula Hajj-Ali, MD

Giant cell arteritis (GCA) is the most common form of systemic vasculitis, affecting an estimated 2.6 in 100,000 people. This unique disease impacts people over the age of 50, most commonly when they reach their 70s.

GCA affects large blood vessels, especially cranial branches of the aorta, and can manifest as headache or jaw pain. It holds the risk of permanent blindness.

Beyond glucocorticoids

While glucocorticoids (GCs) are the cornerstone of therapy and can reduce the risk of visual loss, they’re also toxic, especially for older patients. Relapses are common in GCA, and given the side effects of GCs, adjunctive treatment options are highly necessary. To date, conventional agents such as methotrexate have not been particularly effective.

As the role of biologics in the treatment of rheumatic diseases expands, researchers have studied TNF alpha inhibitors in GCA. Research shows increased expression of TNF alpha in the temporal artery specimens of patients with GCA. But virtually all clinical trials using TNF alpha inhibitors have failed in these patients, and their use is not recommended.

Promise in biologics?

More recently, interleukin-6 inhibitors have showed increasing promise in treating large vessel vasculitis. Tocilizumab (TCZ), currently the only currently approved interleukin-6 receptor antibody, has demonstrated efficacy in a small series of patients with relapsing/refractory GCA and later with patients with newly diagnosed GCA. In 2015, the first randomized controlled trial showed TCZ’s efficacy for inducing and maintaining remission in GCA.  Relapse-free survival in the treatment group reached 85 percent versus 20 percent in the placebo group. Frequent adverse events (seven serious events among 20 patients in the treatment arm) necessitate more definitive results on the safety and efficacy of TCZ in GCA. A phase III, multicenter, randomized, double-blind, placebo-controlled study of TCZ in GCA is underway. (GiACTA – Clinicaltrials.gov identifier: NCT01791153). While not available for peer review, sponsor-released preliminary results suggest efficacy.

Other biologic therapeutics are also of interest in this disease state. A multicenter clinical trial evaluating the efficacy of abatacept for GCA was recently completed. In this study, both relapse-free survival at 12 months (48 percent vs. 31 percent) and median duration of remission (9.9 vs. 3.9 months) were significantly higher among patients receiving abatacept compared with placebo. This remains a pilot study, and replication in larger cohorts is necessary.

Another emerging biologic agent in the treatment of GCA is ustekinumab (a monoclonal antibody to interleukin-12/23p40).  A small open study revealed no relapses during treatment with ustekinumab, but results are too preliminary to advocate for routine usage.

Learn more about best practices and future advances

This is an exciting time for clinicians treating GCA. We have witnessed increasing focus on targeted biologic therapy in this disease and hope that investigations will show alternatives to GC treatment.

Clinicians and advanced practitioners interested in vasculitis should join us for a one day satellite symposium, PRIMARY VASCULITIDES: Best Practices and Future Advances, on April 5, 2017, at the Intercontinental Hotel and Convention Center in Cleveland, Ohio.  This meeting will cover practical issues of diagnosis, treatment and management of various forms of vasculitis including GCA. The meeting will be chaired by Carol Langford, MD, MHS, and Rula Hajj-Ali, MD, and feature a faculty of international experts.

Sign up for updates and registration information at ccfcme.org/primaryvasc

This one day symposium precedes the Biologic Therapies VII Summit: Precision Medicine in the Biologic Era, April 6-8, 2017, InterContinental Hotel and Convention Center, Cleveland, Ohio.

This activity has been approved for AMA PRA Category 1 Credit™.

Dr. Calabrese is Director of the R.J. Fasenmyer Center for Clinical Immunology in Cleveland Clinic’s Department of Rheumatic and Immunologic Diseases.

Dr. Hajj-Ali is a staff physician in the Center for Vasculitis Care and Research and the R.J. Fasenmyer Center for Clinical Immunology in the Department of Rheumatic and Immunologic Diseases.