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GiACTA Longterm

Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial

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Year of Publication: 2021

Authors: John H Stone, Jian Han, Martin Aringer, ..., Min Bao; GiACTA investigators

Journal: The Lancet Rheumatology

Citation: Lancet Rheumatol. 2024; PMID: 38279390

Link: https://doi.org/10.1016/S2665-9913(21)00038-2

PDF: http://www.thelancet.com/article/S2665991321000382/pdf

Clinical Question

What is the durability of tocilizumab effect after discontinuation in giant cell arteritis, and can tocilizumab effectively manage relapses while providing long-term glucocorticoid-sparing benefits?

Study Overview

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

42% of patients treated with weekly tocilizumab for 1 year maintained drug-free remission for 2 years after cessation
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

Patients per Arm

Part two: 215 total; 81 in remission from weekly tocilizumab arm, 59 started part two on no treatment

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

      

Design

Study Type: Open-label extension of randomized controlled trial

Randomization:

Blinding: Unblinded in part two; treatment at investigator discretion

Follow-up Duration: 2 years (part two); 3 years total

Countries:

Sample Size: 215

Analysis: van Elteren test for cumulative glucocorticoid comparisons

Inclusion Criteria

Completion of part one of GiACTA trial
Clinical remission at end of part one (1 year)

Baseline Characteristics

Control (Placebo 26-week taper):

Sample completing part one: Not specified for part two entry

Control (Placebo 52-week taper):

Sample completing part one: Not specified for part two entry

Tocilizumab Weekly:

Patients in remission at year 1: 81
Started part two on no treatment: 59

Tocilizumab Every-Other-Week:

Sample completing part one: Not specified for part two entry

Arms

Field	Tocilizumab Weekly (Part One)	Tocilizumab Every-Other-Week (Part One)	Control	Control	Part Two (Extension)
Intervention	Tocilizumab 162 mg subcutaneous once weekly plus 26-week prednisone taper	Tocilizumab 162 mg subcutaneous every other week plus 26-week prednisone taper	Placebo injections plus 26-week prednisone taper	Placebo injections plus 52-week prednisone taper	Treatment at investigator discretion: no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations
Duration	1 year	1 year	1 year	1 year	2 years

Outcomes

Outcome	Type	Control	Intervention	P-value
Maintenance of clinical remission (absence of relapse) and cumulative glucocorticoid dose over 3 years (exploratory objectives in part two)	Primary			≤0.001 (TCZ weekly vs placebo); <0.05 (TCZ every-other-week vs placebo)
Drug-free remission maintenance (tocilizumab weekly arm patients starting part two on no treatment)	Secondary	N/A	25/59 (42%) maintained tocilizumab-free and glucocorticoid-free remission throughout part two
Median time to remission after relapse - Tocilizumab alone	Secondary	N/A	15 days (n=17)
Median time to remission after relapse - Tocilizumab plus glucocorticoids	Secondary	N/A	16 days (n=36)
Median time to remission after relapse - Glucocorticoids alone	Secondary	54 days (n=27)	N/A
Overall Safety	Adverse	No new or unexpected findings	No new or unexpected findings over full 3 years

Subgroup Analysis

Not reported in abstract

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

Funding

F Hoffmann-La Roche

Based on: GiACTA Longterm (The Lancet Rheumatology, 2021)