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THU0293 Safety and Efficacy of Short-Term Treatment with Tocilizumab in Patients with Refractory Takayasu Arteritis
  1. P. Novikov1,
  2. I. Smitienko2,
  3. A. Elonakov3,
  4. G. Koilubaeva4,
  5. S. Moiseev1
  1. 1Sechenov First Moscow State Medical University
  2. 2Russian Peoples' Friendship University
  3. 3Moscow's regional research clinical institute n.a. M.F. Vladimirskiy, Moscow, Russian Federation
  4. 4National Center for Cardiology and Therapy, Bishkek, Kyrgyzstan

Abstract

Background Takayasu arteritis (TAK) is a granulomatous vasculitis that involves aorta and/or its main branches and usually affects young or middle-aged women (before 50 years of age). Tocilizumab (TOCI) (monoclonal antibodies to IL-6 receptor) is a promising agent for treatment of refractory TAK, also clinical experience is very limited.

Objectives To evaluate the efficacy and safety of short-term treatment with TOCI in patients with TAK refractory to standard immunosuppressive treatment.

Methods We enrolled in our case series all patients with TAK who were treated with TOCI. Diagnosis of TAK was established according to the ACR criteria and CHCC2012. TOCI was administered intravenously at a dosage of 8 mg/kg every 4 weeks. Criteria of efficacy included complete and incomplete remission and relapse of arteritis. Activity of disease was evaluated using the NIH criteria. In all patients, we calculated the Indian Takayasu Clinical Activity Score (ITAS2010).

Results Ten patients with TAK (all females, median age 23.5 years (19-56), type 5 (generalized) in nine patients) were included in retrospective study. Median duration of disease was 48.5 months (29-146). High activity of disease was confirmed by standard laboratory tests (median ESR 56 mm/h, CRP 15.4 mg/L) and MRA/PET/US. Median ITAS score was 5 (3-12), median Kerr index was 2 (1-4). Prior to tocilizumab administration all patients were treated with combination of immunosuppressive drugs (PRED + MTX or MMF or TNF inhibitors (n=3)) for 41 months (16-140).

Average duration of TOCI treatment was 6 months (3-15). Complete and partial remission was achieved in 4 (40%) and 3 (30%) patients, respectively. Median PRED dose was reduced from 30 mg (10-60) to 9.5 mg daily (≤10 mg daily in 5 patients). In 3 patients we observed carotodynias and PRED dose was increased to 10-20 mg. After treatment average ESR and CRP were 12 mm/h and 0.8 mg/L, respectively. Repeated MRA and US confirmed low activity of disease in 5 (71.4%) of 7 patients while in 2 patients (28.6%) MRA showed persistent active vascular inflammation. Median ITAS score declined to 1 (1-5) and median Kerr index to 0 (0-2). TOCI infusions were well-tolerated; we observed 3 cases of carotodynia in few days after infusions; 2 patients developed community-acquired pneumonia and 1 – Herpes zoster infection and purulent bronchitis, with subsequent TOCI dose reduction to 4 mg/kg. In 2 patients surgical vascular intervention was performed (before treatment it was impossible due to active vasculitis). Two patients developed relapse of arteritis when we attempted to increase the dosing interval of TOCI to 6–8 weeks.

Conclusions TOCI is effective in case of active systemic inflammation in patients with refractory TAK. The risk of infections should be taken into account. We observed high rate of carotodynias after TOCI infusions, that requires further confirmation. Long-term results with clinically important end-points (vascular interventions, risk of stenosis progression, long-term outcomes etc.) are awaited.

Disclosure of Interest None declared

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