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Background: Large-vessel vasculitis includes Takayasu arteritis (TAK) and giant cell arteritis. TAK predominantly affects young females and can lead to significant arterial damage over the long term [1]. Glucocorticoids have long been the cornerstone of treatment, used in conjunction with immunosuppressive drugs. Recently, the utility of molecular targeted drugs has been elucidated. Relapse occurs in approximately 60% of patients, with tocilizumab (TCZ) and tumor necrosis factor inhibitors (TNFi) being the preferred molecular targeted drugs in such cases [2, 3]. Most existing data focus on the relatively short-term efficacy of these treatments, and there is limited information on switching between molecular targeted drugs in TAK. Furthermore, due to its approval in Japan, TCZ is the most commonly used molecular targeted drug as first-line therapy for relapsed cases in the country [4].
Objectives: To evaluate the long-term efficacy and safety of molecular targeted drugs in patients with TAK, with a particular focus on the outcomes of switching between different molecular targeted drugs in cases of relapse or inadequate response.
Methods: A retrospective study was conducted involving 121 patients with TAK. These patients met the ACR/EULAR classification criteria or JCS diagnostic criteria. They were treated at Tohoku University Hospital in Sendai, Japan, one of the major centers for TAK treatment in the country, between 2018 and 2024. Clinical backgrounds, the use and switching of molecular targeted drugs, long-term efficacy, and retention rates were analyzed.
Results: Among the 121 patients, 105 (87.6%) were female. The mean age at onset was 33.9 ± 15.2 years, and the mean disease duration was 210 ± 151 months. Type V artery lesions were documented in 35 patients (28.9%), and 39 patients (32.2%) underwent vascular surgery. Molecular targeted drugs were used in 50 patients (41.3%), 47 of whom were initiated on these therapies due to TAK relapse. Patients receiving molecular targeted drugs were characterized by younger age at onset (28.3 ± 12.5 years), a higher frequency of type V artery lesions, and a greater prevalence of extra-arterial comorbidities. Extra-arterial manifestations included ulcerative colitis (n=8), arthritis (n=4), and hearing loss (n=4). The molecular targeted drugs used included TCZ (38 patients), TNFi (14), JAK inhibitors (3), abatacept (2), rituximab (1), and ustekinumab (2). Eight patients required more than two molecular targeted drugs, and four required three or more. During a median follow-up of 57 months after initiating molecular targeted therapy, retention rates were as follows: TCZ, 73.7%; TNFi, 85.7%. Despite the high retention rate of TCZ, seven patients with worsening vascular lesions, relapses without vascular changes, or severe infections did not switch to another class of molecular targeted drugs due to the absence of clear guidance in the 2017 Japanese treatment guidelines. Discontinuation of TCZ was more frequent in patients undergoing vascular surgery or with extra-arterial comorbidities. TCZ was discontinued in 10 patients due to the following reasons: infection (n=3), major relapse (n=4), exacerbation of extra-arterial manifestations (n=2), and drug side effects (n=1). Among these patients, six switched to TNFi as second-line therapy, and one switched to rituximab. All patients who switched to TNFi from TCZ are continuing to use TNFi in combination with a low dose of prednisolone (PSL). Regarding safety profiles, severe colitis occurred in three patients treated with TCZ, and infective endocarditis was documented in two. The mean daily dose of PSL significantly decreased among patients receiving molecular targeted drugs: pre-initiation, 10.6 ± 4.3 mg/day; at initiation, 22.3 ± 10.2 mg/day; and most recently, 4.7 ± 3.8 mg/day. Eleven patients treated with TCZ discontinued PSL, and nine of them remained relapse-free without progression on vascular imaging.
Conclusion: Molecular targeted drugs demonstrated high retention rates and effectively maintained remission while reducing glucocorticoid doses in relapsed TAK cases. The transition from TCZ to TNFi showed satisfactory results but was limited by a lack of supporting evidence. These findings highlight the need for further research to expand therapeutic options and optimize switching strategies in TAK management.
REFERENCES: [1] Mutoh T, Shirai T, Ishii T et al. Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis. Nat Commun. 2020;11:1253.
[2] Shirai T, Sato H, Fujii H et al. The feasible maintenance dose of corticosteroid in Takayasu arteritis in the era of biologic therapy. Scand J Rheumatol. 2021;50:462-468.
[3] Mutoh T, Shirai T, Fujii H et al. Insufficient Use of Corticosteroids without Immunosuppressants Results in Higher Relapse Rates in Takayasu Arteritis. J Rheumatol. 2020;47:255-263.
[4] Shirai T, Ishii T, Okazaki S et al. Active withdrawal of corticosteroids using tocilizumab and its association with autoantibody profiles in relapsed Takayasu arteritis: a multicentre, single-arm, prospective study (the Ab-TAK study). Front. Immunol. 2025; 15:1473100.
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (