Clinical Trial: Efficacy and Tolerance of Tocilizumab In Takayasu Arteritis

Study Status: Terminated
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Efficacy and Tolerance of First-line Treatment With Tocilizumab in Active Takayasu Arteritis French Prospective Multicenter Study

Brief Summary: First-line tocilizumab treatment during 6 months could permit rapid steroid-tapering and induction of remission in Takayasu arteritis (TA).

Detailed Summary:

Scientific/Medical Rationale Takayasu arteritis (TA) is a large-vessel vasculitis that affects the aorta and its primary branches and may lead to arterial segmental stenosis, occlusion and/or aneurism formation. The symptoms are either non specific and reflect systemic inflammation, or related to vascular injury and induced organ-ischemia. Even though many patients respond to glucocorticoids, relapses or steroid-dependence may necessitate the use of combination therapy. Azathioprine (2 mg/kg/day) and methotrexate (20-25 mg/week) have been used in patients with TA, and can induce disease remission and prevent the development of new arterial lesions. The addition of other immunosuppressive agents to glucocorticoids could be required in majority of patients. Magnetic resonance imaging constitutes an interesting non-invasive imaging to assess arterial changes during follow-up.

The pathogenesis of TA includes vessel injury mediated by T-cells, natural killer cells, γδ-T cells and macrophages. T-cells and macrophages infiltrates contribute to granuloma and giant cells formation, and produce IFNγ which stimulate the production of pro-inflammatory cytokines. The secretion of pro-inflammatory cytokines, including TNFα and IL-6, is implicated in vascular inflammation and injury in TA.

In the light of these data, several studies have reported the efficacy of TNFα inhibitors in TA, but only one observational study of 15 cases and a few case-reports are available. The investigators have reported the French multicenter experience on infliximab in TA. In this cohort of 15 french TA patients refractory to other immunosuppressive agents with more than 20 mg prednisone daily, infliximab enabled a significant improvement of both clinical and biological features, in addition to having a steroid-sparing effect. Further
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: number of good responders without prednisone after 6-months tocilizumab treatment [ Time Frame: 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of good and partial responders at 3 , 6, 12 months [ Time Frame: one year ]
  • Total dose steroids during 6 months [ Time Frame: 6 months ]
    determined by the area under the curve
  • TA global activity associated with tocilizumab treatment, by the questionnaires: BVAS, PGO, Dei-Tak; [ Time Frame: 18 months ]
  • Clinical response evaluation [ Time Frame: 18 months ]
    Absence of new clinical features and stability or disappearance of baseline features
  • Biological response evaluation [ Time Frame: 18 months ]
    Disappearance of inflammation or decrease of at least 50% (at least two parameters including VS, CRP, fibrinogen)
  • radiological response : PET and MRI at 6, 9 and 12 months [ Time Frame: 12 months ]
  • Patients quality of life associated with tocilizumab treatment, by the quality of life questionnaires: SF-36 [ Time Frame: 18 months ]


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: February 17, 2014
Date Started: April 2014
Date Completion: April 2016
Last Updated: March 27, 2014
Last Verified: December 2013