Background/Purpose

 Giant cell arteritis (GCA) is a primary vasculitis that involves the aorta and its major branches. It usually affects people aged more than 50 years. GCA may be refractory to standard therapy with corticosteroids that, in turn, may be associated with substantial adverse events. Tocilizumab (TCZ) has demonstrated efficacy in single cases or in small series of patients with GCA. Our aim was to assess the efficacy and side-effects of TCZ in a multicenter study of patients with refractory GCA.

Methods

Multicenter open-label study of patients with refractory GCA. TCZ was used because of inadequate response to corticosteroids and in most cases to other therapies. All the patients meet the 1990 ACR criteria for GCA. TCZ therapy was used at standard dose of 8 mg/kg/monthly.

Results:

22 patients (17 women/ 5 men; mean age±SD was 69±8 years) were assessed. Sixteen (73%) of them had a positive temporal artery biopsy. The main clinical features at the time of TCZ onset were: polymyalgia rheumatica (n=15), asthenia (n=7), headache (n=5), constitutional syndrome (n=4), jaw claudication (n=2), visual manifestations (n=2), claudication of the lower limbs (n=1), chest pain (n=1), arthritis (n=1), dyspnea (n=1) and scapular pain (n=1). Fifteen patients also had aortitis. Besides corticosteroids and before TCZ therapy, 19 patients had received several traditional immunosuppressive agents: methotrexate (n=19), azathioprine (n=1) and leflunomide (n=1). In addition, 2 patients had also been treated with other biologic agents before starting on TCZ. One patient received etanercept that was switched to TCZ due to inefficacy. Another patient received infliximab that was switched to rituximab, then to abatacept and finally to TCZ because of inefficacy. Most patients experienced clinical and laboratory improvement within the first 3 months after the onset of TCZ (TABLE). After a median [IQR 25^th-75^th] follow-up of 6 [3-16] months, the erythrocyte sedimentation rate decreased from a median value of 44 [20-81] to 12 [3-20] mm/1^st hour. Similarly, C-reactive protein levels also decreased from a median initial value of 1.9 [1.2-5.4] to 0.2 [0.1-0.9] mg/dL. A corticosteroid sparing effect was also achieved (from a median [IQR] prednisone dose of 18.75 [10-45] mg/day at TCZ onset to 5 [0-7.5] mg/day at last visit). In 3 patients TCZ was discontinued due to severe neutropenia (351 neutrophils/mm³); recurrent pneumonia; and cytomegalovirus infection, respectively. Also, one patient died after the second infusion of TCZ as the result of a stroke in the setting of an infectious endocarditis.

Conclusion

In our series, TCZ seems to be effective in the treatment of GCA refractory to corticosteroids and other immunosuppressive agents.

TABLE

*p<0.05 compare to baseline