INNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATURE

Abstract

The need for further improvement of treatments for Takayasu’s arteritis (TA), the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6) inhibition. The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs) of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively); but the differences failed to reach statistical significance (p = 0.0596). Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label) treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now there is no universal imaging method that could provide comprehensive information on the status of vessels in TA; the standardization of future clinical trials of BAs requires the improvement of methods for evaluating the efficiency of treatment for TA; moreover, monitoring of disease activity should include a comprehensive assessment of clinical data, current laboratory biomarkers, and instrumental imaging techniques, primarily non-invasive ones.