Tocilizumab delays flare, reduces glucocorticoid dose in new-onset giant cell arteritis
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Weekly tocilizumab delays initial flare and reduces glucocorticoid exposure in patients with relapsing and new-onset giant cell arteritis, according to data published in Rheumatology.
“The IL-6 receptor alpha inhibitor tocilizumab was approved for the treatment of patients with GCA, based on positive results from the Giant-Cell Arteritis Actemra (GiACTA) trial,” John H. Stone, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, in Boston, and colleagues wrote. “Subgroup analysis of GiACTA part 1 suggested potential differences in tocilizumab efficacy between new-onset and relapsing disease.”
“Specifically, data from part 1 suggested that tocilizumab dosed weekly (TCZ QW) or every other week (TCZ Q2W) was similarly effective at preventing flares and reducing glucocorticoid exposure at the week 52 time point in patients with new-onset disease,” they added. “In contrast, TCZ QW was more effective than TCZ Q2W for these outcomes in patients with relapsing disease at baseline. One consequence of these findings has been a reluctance on the part of some clinicians to reserve the use of tocilizumab for patients with relapsing disease and to treat patients with newly diagnosed GCA with prednisone monotherapy.”
To analyze the long-term benefits of tocilizumab (Actemra, Genentech) in patients with new-onset or relapsing GCA, as well as examine the effectiveness of weekly tocilizumab versus doses given every other week, Stone and colleagues evaluated data from GiACTA’s 3-year study period. In the first, blinded part of the trial, 250 patients with new-onset or relapsing GCA were randomly assigned to receive tocilizumab weekly, tocilizumab every other week or placebo for 52 weeks, with a prednisone taper. In part two, 215 patients received treatment based on the researchers’ discretion for 104 weeks.
For this analysis, Stone and colleagues assessed participants based on their initial treatment assignments and examined outcomes beyond week 52. Key outcomes included time to first flare and cumulative glucocorticoid dose during the 3-year study period according to baseline disease status.
According to the researchers, 48% of participants demonstrated new-onset disease, and 52% had relapsing disease, at baseline. Among patients treated with weekly tocilizumab, the median time to initial flare was 577 days for those with new-onset GCA, and 575 days for those with relapsing disease. Meanwhile, times to first flare were 479 and 428 days, respectively, in patients treated with tocilizumab every other day, and 179 and 224 days, respectively, in the placebo group.
The median cumulative glucocorticoid dose in the weekly-tocilizumab group was 3,068 mg in those with new-onset GCA and 2,191 mg in those with relapsing disease, compared with 4,080 mg and 2,353 mg, respectively, among patients treated every other week, and 4,639 mg and 6,178 mg, respectively, in the placebo group.
“The results presented here suggest that treatment with TCZ QW delays time to flare and reduces glucocorticoid exposure in patients with both new-onset and relapsing GCA,” Stone and colleagues wrote. “These results also suggest that TCZ QW should be initiated as soon as possible in patients with GCA, regardless of whether they already have a history of disease at the time of presentation for treatment. A patient with new-onset GCA may later develop relapsing disease, and both patient types deserve optimal therapy to be initiated from the earliest time point after the recognition of active disease.”
Perspective
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Giant cell arteritis treatment has been revolutionized by the landmark GiACTA (Giant Cell Arteritis Actemra) trial. Given that the disease is predominantly seen in patients in the seventh to eighth decade of life, the implications of the treatment – especially lowering the dose of prednisone – are huge.
Up to 80% of patients experience disease flares over the course of 1 year if steroids are tapered completely, and the flare rate is between 35% and 75% even if patients continue on some dose of prednisone while in remission. Therefore, a study designed to evaluate the long-term effects of tocilizumab weekly vs. every other week vs. placebo is very informative. Besides this, cumulative prednisone dose over 3 years, as well as time to first flare while on treatment, are important to clinical practice.
Take-home points from the study from Stone and colleagues are that the benefits of early steroid-sparing treatment with weekly tocilizumab extend beyond 52 weeks. Tocilizumab at all doses demonstrated greater success in postponing time to first flare. Furthermore, weekly tocilizumab has profound effects on reducing cumulative glucocorticoid exposure over the next 3 years in both patients with new-onset GCA and those with relapsing GCA at baseline.
It appears that superior disease control earlier in the disease course improves overall flare rate. Weekly tocilizumab should be initiated as soon as possible in patients with GCA, regardless of whether they are new-onset or relapsing as the treatment provides valuable gains in both disease states.
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