- This post hoc analysis of the GiACTA trial of tocilizumab investigated outcomes separately for patients with new-onset vs. relapsing giant cell arteritis (GCA) over three years, and it compared the effectiveness of dosing weekly vs. every two weeks
- Patients treated with weekly tocilizumab had a longer median time to first disease flare than those who received tocilizumab every two weeks
- The median cumulative glucocorticoid dose was significantly lower for patients who received weekly tocilizumab than those in the placebo group
- These findings were consistent regardless of whether patients had new-onset or relapsing disease at the time of tocilizumab initiation
- These results confirm the benefits of early treatment with weekly tocilizumab to control GCA for the longest time possible without glucocorticoid therapy
U.S. approval of tocilizumab for the treatment of giant cell arteritis (GCA) was based on positive results from GiACTA, a randomized, placebo-controlled, multicenter phase 3 study of patients with new-onset or relapsing GCA. The trial had two parts:
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- In the 52-week double-blind phase (n=250), tocilizumab administered weekly or every two weeks (Q2W) in combination with prednisone taper was superior to placebo plus prednisone taper at inducing sustained remission, while significantly reducing the cumulative glucocorticoid dose (reported in The New England Journal of Medicine)
- In the 104-week open-label extension phase (n=215, treated according to investigator discretion), patients who continued to receive tocilizumab experienced fewer flares and, over the three-year study period, maintained a lower cumulative glucocorticoid exposure than those who received placebo in the double-blind phase (reported in Lancet Rheumatology)
Subgroup analysis of the double-blind phase showed that weekly dosing of tocilizumab was more effective than Q2W dosing for patients with relapsing GCA at baseline, whereas there was no difference between the tocilizumab dosing schedules in outcomes for patients with new-onset disease.
John H. Stone, MD, MPH, director of Clinical Rheumatology at Massachusetts General Hospital, was the lead investigator of both phases of GiACTA. Recently he and colleagues took a deeper dive into the trial data to determine whether the differences in outcomes according to tocilizumab dosing persisted over time. In Rheumatology (Oxford), they report long-term benefits of weekly over Q2W tocilizumab dosing, not only for patients with relapsing disease but also for those with new-onset disease.
The researchers evaluated patients according to their original treatment assignments, and outcomes were assessed from baseline until the end of the three-year study. About half of all patients (weekly tocilizumab group, 47%; Q2W tocilizumab group, 53%; placebo group, 46%) had new-onset disease at baseline, defined as diagnosis ≤6 weeks before tocilizumab initiation.
Time to First Flare After Remission
Weekly tocilizumab was associated with the longest median time to first flare, regardless of whether patients had new-onset or relapsing GCA at baseline:
- New-onset disease at baseline—577 days with weekly tocilizumab, 479 days with Q2W tocilizumab, and 179 days with placebo
- Relapsing disease at baseline—575, 428, and 224 days
The median cumulative glucocorticoid dose was lower for patients who received weekly tocilizumab than those receiving placebo, again regardless of the duration of disease at baseline:
- New-onset disease at baseline—3,068 mg with weekly tocilizumab (P=0.0331 vs. placebo), 4,080 mg with Q2W tocilizumab (P=0.3233 vs. placebo), and 4,639 mg with placebo
- Relapsing disease at baseline—2,191 mg with weekly tocilizumab (P=0.0331 vs. placebo), 2,352 mg with Q2W tocilizumab (P=0.3233 vs. placebo), and 6,178 mg with placebo
Guidance for Prescribers
GCA is a long-term, chronic disease for many patients, almost exclusively older adults in whom the potential for glucocorticoid toxicity is particularly worrisome. The results of this study confirm the benefits of early treatment with weekly tocilizumab. Controlling GCA for the longest time possible without needing to resume glucocorticoid therapy will help prevent complications of both the disease and its treatment.
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