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TAKT Longterm

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

Year of Publication: 2020

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

Journal: Rheumatology

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


Clinical Question

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

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 study of 36 patients with refractory Takayasu arteritis treated with 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
  • 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 profile consistent with known tocilizumab adverse events, with infections being most common

Design

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

Randomization: 1

Blinding: Open-label extension

Follow-up Duration: 96 weeks

Centers: 0

Countries: Japan

Sample Size: 36


Inclusion Criteria

  • Patients with refractory Takayasu arteritis who completed the initial randomized controlled phase of the TAKT study

Arms

FieldTocilizumab 162 mgControl
InterventionTocilizumab 162 mg subcutaneously weekly for up to 96 weeksGlucocorticoids alone (from initial randomized phase)
Duration96 weeksVariable

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Glucocorticoid dose reduction at 96 weeksPrimary0.223 mg/kg/day (baseline relapse dose)0.105 mg/kg/day at 96 weeks; 46.4% achieved <0.1 mg/kg/day
Imaging evaluation at 96 weeksSecondary17.9% improved, 67.9% stable, 14.3% worsened
SF-36 quality of lifeSecondaryClinically meaningful improvements sustained over 96 weeks
Relapse rateSecondary18 relapses in 14 patients (29.4 events per 100 patient-years)
InfectionsAdverseMost common adverse event

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 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)

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

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