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

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. Furthermore, early response was notable, since clinical, biological remission and steroid-sparing were achieved within 3 months in the investigators refractory TA patients.

The importance of targeting pro-inflammatory cytokines in TA was recently raised by the report of the efficacy of the humanized anti-IL6 receptor antibody (tocilizumab). Likewise to TNF-α inhibitors, a dramatic and rapid improvement in clinical manifestations and on laboratory parameters was noted. This early response in even long-standing TA disease, as also noted in the investigators study and in previous reports, supports the use of cytokine-targeting therapies in TA.

Like other immunosuppressive agents in TA, TNF-α inhibitors and tocilizumab were used mostly in refractory TA disease, and thus its benefits as a first-line treatment option, particularly with regard to their steroid-sparing effect and in prevention of relapses, could not be assessed.