Saturday’s “A Guide to Navigating the Waters of Giant Cell Arteritis and Polymyalgia Rheumatica” session included a look at the potential use of tocilizumab, which has received FDA designation as a breakthrough therapy for these conditions.
Rebecca L. Manno, MD, MHS, Associate Professor of Medicine at Johns Hopkins University in Baltimore and Assistant Director of the Johns Hopkins Vasculitis Center, delivered the talk as part of the ACR Review Course.
Tocilizumab, a monoclonal antibody against interleukin 6 (IL-6), is under investigation for treating both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). Increased production of IL-6 correlates with high disease activity in both diseases, and steroid treatment alone does not completely normalize IL-6 production.
In October of this year, the FDA designated tocilizumab a so-called breakthrough therapy because preliminary data indicate the drug may be more effective than existing therapies. The implication of this designation is that the FDA may expedite the development and review of tocilizumab, Dr. Manno said.
During her presentation, Dr. Manno defined GCA as systemic vasculitis of medium and large arteries for which age over 50 years is a key risk factor, with a peak incidence in patients between the ages of 70 and 80 years. The lifetime risk of GCA in the United States is 1.04 percent in women and 0.5 percent in men.
“GCA is a form of arteritis that affects the aorta and other major arteries, including the carotid, vertebral, and temporal arteries. The inflammation is generally granulomatous, and GCA is commonly associated with PMR,” she said.
Large-vessel imaging has a role in the diagnosis of GCA, including conventional and CT angiography, MRI and MRA, and 18-FDG (fludeoxyglucose) PET CT, which appears to be the most promising modality for GCA, Dr. Manno said.
“Temporal artery biopsy is the gold standard for the diagnosis of GCA,” she noted.
Patients who have negative results from a temporal artery biopsy and symptoms of large vessel involvement, such as claudication and asymmetric blood pressure pulses and bruits, should undergo imaging of the thoracic aorta and branch vessels to “investigate the possibility of aneurysm or occlusive disease in these vessels,” according to guidelines from the American College of Cardiology and the American Heart Association.
PMR is an inflammatory syndrome that targets the shoulder, neck, and pelvic girdle region of the body that also occurs in similar age groups as GCA patients. Its incidence in people over 50 years of age is 41 to 68 per 100,000. The lifetime risk of PMR is 2.43 percent in women and 1.66 percent in men.
In addition to age and symptoms of pain in the shoulder, neck, and hip areas, common factors associated with PMR are prolonged morning sickness, an elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP) levels on blood tests, and rapid responses to low-dose prednisone.
High-dose prednisone should be the initial treatment of GCA, but PMR requires low-dose prednisone. In addition, the ACR and the European League Against Rheumatism (EULAR) have conditionally recommended considering early therapy for PMR with methotrexate plus glucocorticoids (GCs), especially in patients at high risk for relapse or prolonged therapy.
Clinical trials of the use of methotrexate (MTX) for GCA patients indicate that the drug may lower the risk of an initial relapse, increase the rate of glucocorticoid-free remission, and allow a lower dose of glucocorticoids.
Recommendations for PMR treatment from the ACR and EULAR state, “Moderate- to high-quality data support the use of IM GCs and MTX as GC-sparing agents in PMR, whereas several treatment aspects such as initial GC doses and tapering regimen have not, or only inadequately, been investigated.”