Sustained inflammation of the aortic wall despite tocilizumab treatment in two cases of Takayasu arteritis

Sir, Takayasu arteritis (TA) is a chronic inflammatory arteritis affecting predominantly the aorta and its main branches, leading to wall thickening, followed by stenosis [1]. Only half of patients respond when treated with glucocorticosteroids (GCs) [2]. We report on two women with TA treated with the IL-6 antagonist tocilizumab (TCZ) after previous treatment attempts with GCs, DMARDs, CYC and TNF-α antagonists failed. Patient 1 (45 years old) was diagnosed in August 2000 as TA presenting with cephalgia, limb claudication and hypertension. GC treatment was started, followed by MTX, since AZA was not tolerated. Renal artery involvement was treated by percutaneous transluminal stent placement. Relapse (8 years later) including severe aortitis was treated by steroid pulses followed by CYC, infliximab and adalimumab. In December 2011, MRI disclosed relapsing thoracic and abdominal aortitis clinically accompanied by B symptoms. Follow-up MRI performed in January 2012 showed a new 60% stenosis of the right common carotid artery, while inflammatory markers increased (ESR 88 mm/h, CRP 3.6 mg/dl). At this point, rescue treatment with TCZ (8 mg/kg) was initiated. GCs were given at a stable dose of 10 mg of prednisolone. Patient 2 (21 years old) was diagnosed in November 2010 as TA presenting with abdominal pain, diarrhoea and high-activity serological markers. MRI showed stenotic changes in the abdominal aorta, including the left renal artery, coeliac trunk and superior mesenteric artery. After insufficient response to CYC and infliximab, rescue therapy with TCZ in addition to MTX was initiated in June 2012. The patient refused to take GCs. ESR and CRP served as serological response markers, and the clinical activity was assessed using the BVAS and the Disease Extent Index for Takayasu Arteritis (DEI.Tak) [3]. Vascular inflammation was monitored by MRI of the aorta before and during therapy. Written consent for publication was obtained from both patients. Despite a decrease in serological markers, BVAS and DEI.Tak, the MRI findings did not improve consistently. In fact, deterioration in both patients could be seen (Fig. 1). A reduction of the thickening of the aortal walls as observed in the first published case of successful TCZ treatment reported by Nishimoto et al. [4] was not seen in our patients. Salvarani et al. [5] confirmed the promising results by showing, in addition to satisfactory clinical and laboratory response, significant improvement in PET/CT findings in two cases with TA. A report of two patients with TA described rapid resolution of large vessel vasculitis [6]. A closer look at the results of both case series showed, however, that in contrast to the patients with GCA, none of the TA patients responded with a complete remission on MRI or PET/CT findings. Clinical and serological course with corresponding MRI findings. (a) ESR, CRP and BVAS persistent score, BVAS new/worse score and DEI.Tak score during TCZ treatment (8 mg/kg every 4 weeks) showing a laboratory and clinical response in patient 1. *ESR not applicable; +: TCZ paused for 8 weeks because of severe respiratory infection; #: TCZ paused for 1 week because of common cold. MRI of the abdominal aorta (axial fat-suppressed T1-weighted post-contrast in black-blood technique in March 2012 and at follow-up MRI in August 2012 showing an increase in inflammation despite therapy). (b) ESR, CRP and BVAS persistent score, BVAS new/worse and DEI.Tak score during TCZ treatment showing a laboratory and clinical response in patient 2. MRI of the abdominal aorta (axial fat-suppressed T1-weighted post-contrast in black-blood technique in May 2012 and at follow-up MRI in September 2012 showing an increase in inflammation despite therapy). This is the first report that illustrates an increase in the thickness and enhancement of the aortic wall during TCZ therapy. Both cases pointed out that therapeutic success should not be monitored only by ESR/CRP or BVAS. Even the use of the DEI.Tak, which seems to be more accurate in describing the clinical abnormalities in Takayasu patients, may lead to wrong assumptions. Imaging techniques are needed to observe treatment response, especially with the use of IL-6 antagonists. Furthermore, it has been shown that there is still a need for new therapeutic regimens in TA. Disclosure statement: The authors have declared no conflicts of interest.