GiACTA Longterm
(2021)Objective
To explore maintenance of efficacy 1 year after discontinuation of tocilizumab, effectiveness of retreatment after relapse, and long-term glucocorticoid-sparing effect in giant cell arteritis
Study Summary
• Tocilizumab significantly reduced cumulative 3-year glucocorticoid exposure (2647 mg vs 5277-5323 mg for placebo groups, p≤0.001)
• Tocilizumab-based regimens restored remission faster after relapse (15-16 days) compared to glucocorticoids alone (54 days)
Intervention
Open-label extension with treatment at investigator discretion: tocilizumab, glucocorticoids, methotrexate, combinations, or no treatment
Inclusion Criteria
Patients completing part one of GiACTA trial who achieved clinical remission at 1 year
Study Design
Arms: Tocilizumab 162mg SC weekly, Tocilizumab 162mg SC every other week, Placebo + 26-week prednisone taper, Placebo + 52-week prednisone taper (from part one); Part two treatment at investigator discretion
Patients per Arm: Part two: 215 total; 81 in remission from weekly tocilizumab arm, 59 started part two on no treatment
Outcome
• Median cumulative glucocorticoid dose over 3 years: 2647 mg (weekly TCZ) vs 5277-5323 mg (placebo groups)
• No new or unexpected safety findings over full 3 years
Bottom Line
42% of patients treated with tocilizumab weekly for one year maintained drug-free remission for two years after stopping treatment. Tocilizumab significantly reduces long-term glucocorticoid exposure and rapidly restores remission in patients who relapse.
Major Points
- Part two was a 2-year open-label extension following the 1-year randomized controlled part one
- 215 patients participated in part two; 81 patients from the weekly tocilizumab group were in remission
- 59 patients who achieved remission on weekly tocilizumab started part two on no treatment
- 25/59 (42%) maintained tocilizumab-free and glucocorticoid-free remission throughout the 2-year extension
- 3-year cumulative glucocorticoid dose was approximately halved with weekly tocilizumab vs placebo
- Tocilizumab-based regimens restored remission in median 15-16 days vs 54 days with glucocorticoids alone
- No new or unexpected safety signals over 3 years of observation
- Results support that continuous indefinite immunosuppression is not required for all GCA patients
Study Design
- Study Type
- Open-label extension of randomized controlled trial
- Randomization
- No
- Blinding
- Unblinded in part two; treatment at investigator discretion
- Sample Size
- 215
- Follow-up
- 2 years (part two); 3 years total
Primary Outcome
Definition: Maintenance of clinical remission (absence of relapse) and cumulative glucocorticoid dose over 3 years (exploratory objectives in part two)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| - | - | - (See individual arms) | ≤0.001 (TCZ weekly vs placebo); <0.05 (TCZ every-other-week vs placebo) |
Limitations & Criticisms
- Open-label design in part two introduces potential bias in treatment decisions and outcome assessment
- Treatment in part two was at investigator discretion, limiting comparability across groups
- Exploratory objectives only; not powered for statistical comparisons in extension phase
- Baseline characteristics for part two entry not fully detailed
- Selection bias: only patients who completed part one and achieved remission entered extension
Citation
Lancet Rheumatol. 2024; PMID: 38279390