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TAKT Longterm

Q: What were the key findings of the TAKT Longterm trial?

Tocilizumab 162 mg weekly for up to 96 weeks demonstrated significant steroid-sparing effects, with nearly half of patients achieving very low glucocorticoid doses, improved quality of life, and stable or improved vascular imaging with acceptable safety profile.

Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study

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Year of Publication: 2020

Authors: Yoshikazu Nakaoka, Mitsuaki Isobe, Yoshiya Tanaka, ..., Norihiro Nishimoto

Journal: Rheumatology

Citation: Rheumatology 2020;59:2427–2434

Link: https://doi.org/10.1093/rheumatology/kez630

PDF: https://academic.oup.com/rheumatology/ar...6221/kez630.pdf

Clinical Question

Does long-term treatment with tocilizumab provide sustained steroid-sparing effects and maintain safety in patients with refractory Takayasu arteritis?

Study Overview

Objective

To investigate the long-term efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis

Study Summary

Tocilizumab 162 mg weekly showed steroid-sparing effect with 46.4% of patients reducing glucocorticoid dose to <0.1 mg/kg/day by 96 weeks
Most patients (85.7%) had improved or stable disease on imaging evaluation after 96 weeks
Patient quality of life improved and was maintained throughout treatment with no new safety concerns

Intervention

Tocilizumab 162 mg subcutaneous weekly

Patients per Arm

36 patients total (all received tocilizumab in extension phase)

Bottom Line

Tocilizumab 162 mg weekly for up to 96 weeks demonstrated significant steroid-sparing effects, with nearly half of patients achieving very low glucocorticoid doses, improved quality of life, and stable or improved vascular imaging with acceptable safety profile.

        Major Points
        Open-label extension of the phase 3 TAKT trial; all 36 patients (previously randomized 18 tocilizumab / 18 placebo in double-blind period) received tocilizumab 162 mg subcutaneously weekly
Median glucocorticoid dose reduced from 0.223 mg/kg/day at baseline relapse to 0.105 mg/kg/day at 96 weeks (mean difference –0.120 mg/kg/day; 95% CI –0.154, –0.087)
46.4% of patients achieved glucocorticoid dose reduction to <0.1 mg/kg/day by week 96
85.7% of patients had improved (17.9%) or stable (67.9%) disease on imaging evaluation at 96 weeks
SF-36 quality of life scores showed clinically meaningful improvements that were sustained over 96 weeks
18 relapses occurred in 14 patients during the extension period (29.4 events per 100 patient-years)
Safety: infections/infestations 88.9% (218.8/100 PY), serious AEs 25% (17.4/100 PY); no withdrawals due to AEs

      

Design

Study Type: Open-label extension of randomized controlled phase 3 trial

Randomization: 1

Blinding: Open-label extension (double-blind during initial phase)

Enrollment Period: Informed consent from 24 September 2014; study end September 2017

Follow-up Duration: Up to 96 weeks or longer; median tocilizumab exposure 108.07 weeks (double-blind + open-label)

Countries: Japan

Sample Size: 36

Inclusion Criteria

Aged ≥12 years at time of informed consent
Confirmed diagnosis of Takayasu arteritis per 2008 Japanese Guideline for Management of Vasculitis Syndrome
Relapse within the previous 12 weeks despite oral glucocorticoid treatment at prednisolone-equivalent dose ≥0.2 mg/kg/day
Completed the double-blind, placebo-controlled period of the TAKT trial

Baseline Characteristics

Characteristic	Control	Active
Note	Extension is single-arm (all patients on tocilizumab); no concurrent control in extension. Baseline data shown for the pooled cohort (n=36) at start of double-blind period.
Female (%)		86.1
Mean age (years)		30.9
Mean disease duration (years)		5.02
HLA-B52 positive (%)		55.6
Inflammatory bowel disease		None

Arms

Field	Tocilizumab (open-label extension)
Intervention	Tocilizumab 162 mg subcutaneously weekly
Duration	Up to 96 weeks or longer (median tocilizumab exposure 108.07 weeks including double-blind period); n=36 entered extension, n=28 completed 96 weeks

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR
Glucocorticoid dose reduction at 96 weeks (vs dose at relapse before study entry)	Primary	0.223 mg/kg/day (median dose at relapse before study entry; IQR 0.207, 0.238)	0.105 mg/kg/day at 96 weeks (IQR 0.039, 0.153); 46.4% achieved <0.1 mg/kg/day	-0.12
Imaging evaluation at 96 weeks (n=28)	Secondary		Improved 17.9% (5/28), stable 67.9% (19/28), worsened 14.3% (4/28)
SF-36 physical and mental component summary scores	Secondary		Clinically meaningful improvements (MCID >2.5) from baseline; sustained through 96 weeks; 7 of 8 domain scores improved
Relapse rate during open-label extension	Secondary		18 relapses in 14 patients (29.4 events per 100 patient-years)
Infections/Infestations	Adverse		88.9% of patients; 218.8 events/100 PY (most frequent AE category)
Serious Adverse Events	Adverse		25% of patients; 17.4 events/100 PY
Gastroenteritis (serious)	Adverse		5.6%; 2.9/100 PY
Pneumonia (serious)	Adverse		5.6%; 2.9/100 PY
Withdrawals due to AE	Adverse		None

Criticisms

Data collected at randomization were used as baseline rather than first tocilizumab dose for patients who received placebo during double-blind period
Small sample size of 36 patients limits generalizability
Open-label design introduces potential bias
No concurrent control group during extension period
Four patients showed worsened imaging at 96 weeks, highlighting need for regular monitoring
Limited frequency of imaging examinations due to safety and cost considerations
Need for biomarkers to facilitate early detection of patients requiring therapy modifications

Funding

Chugai Pharmaceutical Co. Ltd

Based on: TAKT Longterm (Rheumatology, 2020)