Younge et al found that certain factors and combinations of factors could be highly predictive of temporal artery biopsy results, including jaw claudication, new headache, scalp tenderness, and decreased vision.
In one series, approximately 9% of patients with negative biopsy subsequently were diagnosed with giant-cell arteritis, “so that unfortunately can occur.” One variant of giant-cell arteritis tends to affect the large vessels leaving the aorta and to spare the temporal arteries, which could lead to a negative biopsy. The most common cause of a negative biopsy, however, is that “it is a different diagnosis.”
“If the biopsy is negative, but you suspect this [disorder] very, very strongly, then continue the treatment because then there should be a marked improvement in symptoms within a week.” As this is an autoimmune disorder, consultation with a rheumatologist is usually helpful.
Imaging studies are not part of routine testing, but FDG PET may be useful in making the diagnosis.
Old and New Therapies
The FDA has not approved medications specifically for giant-cell arteritis. The mainstay of treatment is corticosteroids. Rheumatologists principally treat giant-cell arteritis, and neurologists should involve them early in the process, Dr. Swanson said.
Low-dose aspirin is frequently added for its antiplatelet effect, and this practice is supported by observational studies. Follow-up includes monitoring and treating the effects of glucocorticoids. Once glucocorticoid therapy is initiated, the risk of blindness is estimated to be about 1%.
To avoid corticosteroid or glucocorticoid adverse effects, such as osteopenia and bone fracture, methotrexate has been used. Three studies using methotrexate have shown reductions in the cumulative dose of glucocorticoid over 48 weeks and a reduced risk of relapse after prednisone is stopped. It takes 24 to 36 weeks for methotrexate to have its full anti-immune effect, Dr. Swanson noted.
Several case series have reported that tocilizumab, a humanized monoclonal antibody that targets interleukin 6, may be effective in patients in whom it has been difficult to taper glucocorticoids to an acceptable level or who have had refractory or relapsing disease. Controlled trials of this drug are under way, and “it will be important to have those results to know if this [drug] is in fact worthwhile,” Dr. Swanson said.
Results from a randomized, double-blind, placebo-controlled trial of tocilizumab in giant-cell arteritis were published online ahead of print March 4 in Lancet. In the phase II trial, 20 patients received IV tocilizumab and 10 patients received placebo infusions at four-week intervals for a year. Both groups received oral prednisolone. At 12 weeks, 85% of patients in the tocilizumab group achieved complete remission of disease, compared with 40% of patients in the placebo group. By 52 weeks, 85% of patients in the tocilizumab group achieved relapse-free survival, compared with 20% in the placebo group. The mean cumulative prednisolone dose was 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group. Rates of serious adverse events were higher in the placebo group than in the active treatment group. These preliminary results suggest that tocilizumab may become an important new management tool, Dr. Swanson said.
Cyclophosphamide has been used in patients at high risk of glucocorticoid-related adverse effects who have not responded adequately to other agents. In a meta-analysis of 88 cases, 84% of patients responded to cyclophosphamide, but 19% relapsed and 2.5% discontinued the therapy because of adverse effects.
Several other potential treatments may be on the horizon, including abatacept, a novel fusion protein that consists of cytotoxic T lymphocyte antigen (CTLA) linked to a modified heavy-chain constant region of human immunoglobulin G1; anakinra, which blocks the biologic activity of interleukin-1 (IL-1) by competitively inhibiting IL-1 binding to the IL-1 type I receptor; and gevokizumab, a humanized anti-IL-1β monoclonal antibody. Randomized trials have found that tumor necrosis factor inhibition therapies, including infliximab, etanercept, and adalimumab, are not effective in giant-cell arteritis.
—Jake Remaly