Vascular imaging of patients with refractory Takayasu arteritis treated with tocilizumab: post hoc analysis of a randomized controlled trial

Abstract

Objectives Tocilizumab, an anti–interleukin-6 receptor antibody, was investigated in patients with refractory Takayasu arteritis (TAK) in a phase 3 randomized controlled trial. In this post hoc analysis, we investigated whether tocilizumab treatment inhibited the progression of vascular lesions caused by TAK in these patients. Methods Included patients received at least one dose of tocilizumab and underwent computed tomography (CT) at baseline and at week 48 after tocilizumab initiation. Three radiologists not involved in the original trial independently evaluated the CT images. Twenty-two arteries from each patient were assessed for change from baseline in wall thickness (primary end point), dilatation/aneurysm, stenosis/occlusion or wall enhancement for at least 96 weeks after tocilizumab initiation. Patient-level assessments were also conducted. Results In 28 patients, 86.7% of 22 arteries had improved/stable wall thickness at week 96. Proportions of patients with improved/stable, partially progressed or newly progressed lesions were 57.1%, 10.7% and 28.6% for wall thickness; proportions with improved/stable lesions were 92.9% for dilatation/aneurysm and 85.7% for stenosis/occlusion. Patients with newly progressed lesions, reflecting more refractory disease, were prescribed glucocorticoids at dosages that could not be reduced below 0.1 mg/kg/day at week 96. Conclusions ∼60% of patients with TAK did not experience progression in wall thickness within 96 weeks after initiation of tocilizumab treatment. Few patients experienced progressed dilatation/aneurysm or stenosis/occlusion. Wall thickness progression likely resulted from refractory TAK. Patients who experience this should be monitored regularly by imaging, and additional glucocorticoid or immunosuppressive treatment should be considered to avoid vascular progression.

Complexity of Inflammation in the Trajectory of Vascular Disease: Interleukin 6 and Beyond

“…In both the tocilizumab and placebo groups, wall thickening, stenosis (occlusion), enlargement (aneurysm), and contrast effects of 22 vessel segments were compared before double-blind treatment and at the end of the 96-week open-label tocilizumab administration. 20) Among the 28 patients, a total of 57.1% displayed improved or maintained wall thickening; 10.7%, partial progression (worse than baseline) in one or more vessels; and 28.6%, new progression (baseline findings were normal, but wall thickening was observed at 96 weeks).…”

“…The age of onset of the disease is between 10 and 30 years, with a peak in the 20s, and the condition occurs more frequently in women (the male-to-female ratio is approximately 1 : 9). Traditionally, corticosteroids such as prednisolone (PSL) and immunosuppressive drugs have been used to treat Takayasuʼs arteritis, but in the past few years, three clinical studies [18][19][20] and one post-market surveillance study 21) from Japan have evaluated the efficacy of tocilizumab, a humanized antihuman IL-6 receptor monoclonal antibody.…”

Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis

“…In a phase 3 RCT comparing 18 TAK patients each treated with tocilizumab or placebo, the time to relapse was similar between tocilizumab and placebo in the intention-to-treat primary analysis but favored tocilizumab in the per-protocol secondary analysis [ 18 ]. On a longer-term follow-up on these patients, including an open-label extension phase, 60% of TAK treated with tocilizumab experienced a stabilization of angiographic progression [ 124 ]. Observational data also support the use of tocilizumab in TAK [ 15 ].…”

Ultrasound activity score in the carotid arteries for assessing disease activity of Takayasu arteritis

“…The signi cant association of wall thickness and active disease has been supported by multiple studies thereafter [8]. The reduction in circumferential wall thickness in response to treatment has further been reported [9,10]. Nonetheless, there remains a lack of consensus on the added value of ultrasonography in the assessment of TAK disease activity.…”