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Reference: GiACTA (N Engl J Med 2017 Jul 27;377(4):317) (level 1 [likely reliable] evidence)
- First-line therapy for giant cell arteritis (GCA) is high-dose corticosteroids for several weeks followed by a gradual taper. The interleukin-6 (IL-6) receptor antagonist tocilizumab may reduce symptoms and corticosteroid use by interfering with pathogenic pathways.
- In the GiACTA trial, 251 adults with GCA were randomized to 1 of 4 treatment groups for 52 weeks: tocilizumab 162 mg subcutaneous injection either once weekly or once every other week, each with a 26-week prednisone taper, or placebo injection once weekly with either a 26-week or 52-week prednisone taper.
- Sustained remission (no disease flare, C-reactive protein level < 1 mg/dL, and adherence to prednisone taper) was observed in 56% of patients with tocilizumab once weekly, 53% with tocilizumab every other week, 14% with placebo and 26-week taper, and 18% with placebo and 52-week taper (p < 0.001, NNT 3, for each tocilizumab group vs. each placebo group).
GCA is a chronic systemic vasculitis involving large- and medium-sized arteries, most commonly the temporal and other cranial arteries. High-dose oral corticosteroid therapy for several weeks followed by a gradual taper is the first-line treatment, but long-term systemic corticosteroid use is associated with significant adverse events (Curr Treat Options Neurol 2017, Ann Intern Med 2016). Adjunct therapies targeting possible pathogenic pathways such as that mediated by IL-6 may help control symptoms and disease progression and also reduce corticosteroid use (Autoimmun Rev 2017). The effect of the IL-6 receptor inhibitor tocilizumab on GCA was investigated in the Giant-Cell Arteritis Actemra (GiACTA) trial. In this trial, 251 patients ≥ 50 years old taking prednisone 20-60 mg orally daily for GCA (newly diagnosed in 47%) that was active within the past 6 weeks were randomized to 1 of 4 treatment groups for 52 weeks: tocilizumab 162 mg subcutaneous injection either once weekly or once every other week, each with a 26-week prednisone taper, or placebo injection once weekly with either a 26-week or 52-week prednisone taper. During the prednisone taper, patients and trial personnel were blinded to prednisone doses < 20 mg, and placebo tablets were used once the dose reached 0 mg. Randomization was stratified by baseline daily prednisone dose (≤ 30 mg vs. > 30 mg). Disease flare was defined as the recurrence of signs or symptoms of GCA or erythrocyte sedimentation rate ≥ 30 mm/hour that was attributed to GCA. The primary outcome of sustained remission was defined as achieving C-reactive protein levels < 1 mg/dL by week 12, lack of disease flare during weeks 12 to 52, and adherence to the prednisone taper.
At 52 weeks, patients taking tocilizumab had significantly greater rates of sustained remission and lower cumulative corticosteroid doses than patients taking placebo. Consistent results were observed for sustained remission without the low CRP level requirement. Tocilizumab was also associated with reduced rates of serious adverse events.
The GiACTA trial demonstrated that adjunct tocilizumab increases the rate of sustained remission and reduces corticosteroid use in adults with GCA. These results form the basis of the recent FDA approval of tocilizumab for GCA (FDA press release 2017 May 22). Long-term safety and efficacy of tocilizumab in patients with GCA will be assessed during a 2-year open-label follow-up phase of this trial, but it should be noted that tocilizumab has been FDA-approved for rheumatoid arthritis since 2010. In this study, while there was a higher rate of neutropenia with tocilizumab, the rates of infection were similar. Given the potential benefits of adjunct tocilizumab and potentially serious complications of GCA and long-term corticosteroid use, tocilizumab is an additional option to consider for adults with GCA.
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