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)

Overview

Journal Front Immunol

Date 2025 Jan 22

PMID 39840060

Authors

Tsuyoshi Shirai

Tomonori Ishii

Soshi Okazaki

Yuko Shirota

Yusho Ishii

Hiroko Sato

Hiroshi Fujii

Affiliations

Soon will be listed here.

Abstract

Objectives: The feasibility of corticosteroid withdrawal (CW) for Takayasu arteritis (TAK) remains uncertain. Two autoantibodies (Abs) are identified against endothelial protein C receptor (EPCR) and scavenger receptor class B type 1 (SR-BI) in TAK, determining its three subgroups. This study aimed to evaluate CW using tocilizumab (TCZ) and its association with the Ab profile.

Methods: This prospective study, lasted for 24 weeks, included patients with relapsed but stable TAK. Scheduled tapering of prednisolone (PSL) was performed with subcutaneous TCZ (CW at week 20). The primary endpoint was the difference in type A remission, defined by CW and the absence of inflammatory signs, according to the Ab profile at week 24.

Results: Twenty patients were included and 18 patients with a mean PSL dose of 4.9 ± 2.8 mg/day were analysed. Anti-EPCR Ab-positive (E+), anti-SR-BI Ab-positive (S+), and double-negative (DN) groups included four (22.2%), eight (44.4%), and six (33.3%) patients, respectively. At week 24, the mean PSL dose was 2.0 ± 2.7 mg/day. Type A remission was observed in eight patients (44.4%), with significant differences based on the Ab profile: E+ (three patients, 75%), S+ (five patients, 62.5%), and DN (zero patients, 0%) (P=0.018). Besides, age, disease duration, PSL dose, type V arterial lesion, arterial dilation, and C-reactive protein >0.01 mg/dL were identified as risks for CW failure.

Conclusion: CW using TCZ was achieved in 44.4% of patients with TAK relapse and was significantly higher in E+ and S+ patients. CW can be a feasible target, and the precise selection of patients is critical.

References

Goel R, Danda D, Joseph G, Ravindran R, Kumar S, Jayaseelan V . Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: Single centre experience from a large tertiary care teaching hospital in Southern India. Semin Arthritis Rheum. 2017; 47(5):718-726. DOI: 10.1016/j.semarthrit.2017.09.014. View

Liu Y, Zhang H, Zhang T, Yuan M, Du C, Zeng P . Effects of Tocilizumab Therapy on Circulating B Cells and T Helper Cells in Patients With Neuromyelitis Optica Spectrum Disorder. Front Immunol. 2021; 12:703931. PMC: 8360623. DOI: 10.3389/fimmu.2021.703931. View

Shirai T, Hilhorst M, Harrison D, Goronzy J, Weyand C . Macrophages in vascular inflammation--From atherosclerosis to vasculitis. Autoimmunity. 2015; 48(3):139-51. PMC: 4606880. DOI: 10.3109/08916934.2015.1027815. View

Nakaoka Y, Isobe M, Takei S, Tanaka Y, Ishii T, Yokota S . Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2017; 77(3):348-354. PMC: 5867398. DOI: 10.1136/annrheumdis-2017-211878. View

Shirai T, Fujii H, Ono M, Watanabe R, Ishii T, Harigae H . An innovative method to identify autoantigens expressed on the endothelial cell surface: serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF). Clin Dev Immunol. 2013; 2013:453058. PMC: 3562638. DOI: 10.1155/2013/453058. View

Manabe Y, Ishibashi T, Asano R, Tonomura S, Maeda Y, Motooka D . Gut dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis. Arthritis Res Ther. 2023; 25(1):46. PMC: 10037851. DOI: 10.1186/s13075-023-03031-9. View

Shirai T, Fujii H, Ono M, Nakamura K, Watanabe R, Tajima Y . A novel autoantibody against fibronectin leucine-rich transmembrane protein 2 expressed on the endothelial cell surface identified by retroviral vector system in systemic lupus erythematosus. Arthritis Res Ther. 2012; 14(4):R157. PMC: 3580549. DOI: 10.1186/ar3897. View

Shirai T . Common Autoantibody among Takayasu Arteritis and Ulcerative Colitis: A Possible Pathophysiology That Includes Gut-Vessel Connection in Vascular Inflammation. JMA J. 2023; 6(3):265-273. PMC: 10407456. DOI: 10.31662/jmaj.2023-0038. View

Yoshifuji H . Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy. Mod Rheumatol. 2018; 29(2):287-293. DOI: 10.1080/14397595.2018.1546358. View

10.

Shirai T, Murakami K, Fujii H, Ishii T, Harigae H . Comment on: Aortarctia: a rare manifestation of relapsing polychondrits. Rheumatology (Oxford). 2020; 59(7):1784-1785. DOI: 10.1093/rheumatology/keaa019. View

11.

Mutoh T, Ishii T, Shirai T, Akita K, Kamogawa Y, Fujita Y . Refractory Takayasu arteritis successfully treated with rituximab: case-based review. Rheumatol Int. 2019; 39(11):1989-1994. DOI: 10.1007/s00296-019-04390-w. View

12.

Isobe M, Maejima Y, Saji M, Tateishi U . Evaluation of tocilizumab for intractable Takayasu arteritis and F-fluorodeoxyglucose-positron emission tomography for detecting inflammation under tocilizumab treatment. J Cardiol. 2021; 77(5):539-544. DOI: 10.1016/j.jjcc.2020.12.011. View

13.

Gon Y, Yoshifuji H, Nakajima T, Murakami K, Nakashima R, Ohmura K . Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab. Mod Rheumatol. 2020; 31(3):678-683. DOI: 10.1080/14397595.2020.1800560. View

14.

Ramirez G, Rovere-Querini P, Blasi M, Sartorelli S, Di Chio M, Baldini M . PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases. Front Immunol. 2019; 10:1135. PMC: 6548810. DOI: 10.3389/fimmu.2019.01135. View

15.

Kerr G, Hallahan C, Giordano J, Leavitt R, Fauci A, Rottem M . Takayasu arteritis. Ann Intern Med. 1994; 120(11):919-29. DOI: 10.7326/0003-4819-120-11-199406010-00004. View

16.

Kakuta Y, Shirai T, McGovern D, Braun J, Fujii H, Masamune A . Novel Diagnostic Autoantibodies Against Endothelial Protein C Receptor in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2021; 21(3):844-846. DOI: 10.1016/j.cgh.2021.12.035. View

17.

Stone J, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D . Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017; 377(4):317-328. DOI: 10.1056/NEJMoa1613849. View

18.

Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S . Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J. 1987; 6(10):2939-45. PMC: 553729. DOI: 10.1002/j.1460-2075.1987.tb02598.x. View

19.

Hanioka Y, Shimizu K, Yamagami K, Yao S, Nakamura R, Nakamura T . Exacerbation of Ulcerative Colitis with Tocilizumab: A Report of Two Cases, One with Takayasu Arteritis and the Other with Relapsing Polychondritis. Intern Med. 2020; 60(10):1615-1620. PMC: 8188011. DOI: 10.2169/internalmedicine.5215-20. View

20.

Schmidt J, Kermani T, Bacani A, Crowson C, Cooper L, Matteson E . Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Mayo Clin Proc. 2013; 88(8):822-30. DOI: 10.1016/j.mayocp.2013.04.025. View