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I thank Liebling and colleagues for their interest in our manuscript1 and for sharing their experience with a patient with refractory Takayasu arteritis who developed aortic ulceration while on tocilizumab therapy.2 Our first multicentre, randomised, double-blind, placebo-controlled study (the TAKT study) showed a favourable effect for tocilizumab over placebo in patients with refractory Takayasu arteritis. As shown in online supplementary figure S1 of our manuscript,1 the study included patients who did not respond to conventional or biologic disease-modifying antirheumatic drugs, similar to the patient reported by Liebling et al. The data from an open-label extension of this study, the largest prospective clinical trial in patients with Takayasu arteritis, showed the steroid-sparing effect of tocilizumab when the glucocorticoid dose was tapered based on the disease activity of the patient.3 The difference in the exposure-adjusted relapse rate between the double-blind period in which glucocorticoid was mandatorily tapered (203.1 events per 100 patient-years in the placebo group and 101.1 events per 100 patient-years in the tocilizumab group) and the open-label extension period (23.6 events per 100 patient-years) highlights the importance of the glucocorticoid dose reduction rate for the management of this disease, as was previously reported by Ohigashi et al.4 While it is not clearly described in their recent letter, the difference in the speed of glucocorticoid dose tapering while this patient was receiving tocilizumab and other biologics might have influenced her clinical course.
Several reports have indicated that progression of aortic structural damage in patients with Takayasu arteritis may occur without clinical symptoms or elevated inflammatory markers.5 6 Both clinical assessment and serial imaging tests are important for monitoring patients with Takayasu arteritis, especially when receiving tocilizumab as it suppresses the clinical symptoms and normalises acute-phase reactants. In our TAKT study, radiographic progression was observed in some patients while they were receiving tocilizumab with glucocorticoid tapering. It should be noted, therefore, that once radiographic progression is detected, then therapy modification including an increase in glucocorticoid dose or addition of immunosuppressant therapy should be considered in order to prevent further structural remodelling even if there are no signs of relapse.
Finally, the treatment options remain uncertain for patients with Takayasu arteritis who have inadequate responses to the current therapies. Needless to say, some patients with Takayasu arteritis may have an inadequate response to tocilizumab and may benefit from switching to other biologics. As the evidence for the efficacy and safety of the treatments for Takayasu arteritis is currently limited, the evidence-based treatment algorithm for patients with Takayasu arteritis will need to be further explored in the future.
Handling editor Josef S Smolen
Contributors YN wrote the response to the eLetter.
Competing interests YN reports personal fees from Chugai as a consultant for the sponsor-initiated clinical trial (Chugai Pharmaceutical Co., Ltd.) using tocilizumab for Takayasu arteritis; grants and personal fees from Chugai; grants and personal fees from Astellas, Pfizer, AbbVie and MSD outside the submitted work; grants from Takeda, Otsuka and Bayer; and personal fees from Daiichi Sankyo and Kowa Pharmaceutical Co. outside the submitted work.
Patient consent Obtained.
Provenance and peer review Commissioned; internally peer reviewed.
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