Indian Journal of Rheumatology

EDITORIAL
Year
: 2021  |  Volume : 16  |  Issue : 4  |  Page : 373--374

Management of Takayasu arteritis: The elusive search for the holy grail!


Upendra Rathore, Durga Prasanna Misra 
 Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Correspondence Address:
Dr. Durga Prasanna Misra
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
India




How to cite this article:
Rathore U, Misra DP. Management of Takayasu arteritis: The elusive search for the holy grail!.Indian J Rheumatol 2021;16:373-374


How to cite this URL:
Rathore U, Misra DP. Management of Takayasu arteritis: The elusive search for the holy grail!. Indian J Rheumatol [serial online] 2021 [cited 2022 Jan 21 ];16:373-374
Available from: https://www.indianjrheumatol.com/text.asp?2021/16/4/373/333214


Full Text



Takayasu arteritis (TAK) is an enigmatic large vessel vasculitis more commonly encountered in Asia, including in India.[1] Aberrant activation of the immune system is understood to be the mechanism driving the pathogenesis of TAK.[2] However, the medical therapy of TAK yet remains unclear.[3],[4] Assessment of disease activity in TAK also remains challenging.[5] The site of pathology, namely the aorta and its branches remains inaccessible for direct examination, unlike the other form of large vessel vasculitis, giant cell arteritis, where temporal arteries are easily accessible for biopsy or imaging through ultrasound. Therefore, outcome assessment in TAK relies predominantly on clinical remission, whose assessment per se is heterogenous and often discordant with the actual vascular pathology, and stabilization or improvement of the extent of disease on serial angiography.[5],[6] TAK responds well to corticosteroid therapy, however, the disease activity often relapses as corticosteroid therapy is tapered or withdrawn.[7] For this reason, disease-modifying antirheumatic drugs (DMARDs) are often added upfront to maintain remission of disease activity.

Unfortunately, no DMARD has yet shown definitive efficacy or effectiveness in TAK. Few quality randomized controlled trials are available in TAK. Subcutaneous weekly administration of tocilizumab failed to demonstrate superiority against placebo for reduction of time to relapse using an intention-to-treat analysis, however, demonstrated a benefit with tocilizumab in per-protocol analysis.[8],[9] Intravenous abatacept failed to demonstrate superiority versus placebo for time to relapse in another clinical trial.[10] Few observational studies have had suitable control groups for comparison of outcomes in TAK. Limited data in this regard suggest the potential for better clinical response with leflunomide than with cyclophosphamide, comparable clinical responses with leflunomide and methotrexate, similar responses with either antitumor necrosis factor-alpha agents or tocilizumab and better clinical responses (with similar angiographic progression) for tofacitinib versus methotrexate.[11],[12],[13] Pooled comparisons from studies comparing biological DMARDs with conventional DMARDs suggest a potential for better clinical and angiographic response with biological DMARDs, although the results failed to attain statistical significance. Pooled data from uncontrolled observational studies have demonstrated clinical remission or angiographic stabilization in >60% patients treated with tocilizumab, antitumor necrosis factor-alpha agents, azathioprine, and leflunomide with a similar degree of clinical response with mycophenolate mofetil. The lack of an appropriate control group limits the understanding of a majority of observational studies on the management of TAK.[12],[13]

In this context, Shumy et al. reported outcomes in a cohort of 11 patients with active TAK treated with corticosteroids with further addition of methotrexate if there was inadequate control of disease activity, followed up for 6 months and outcomes were assessed at 1 month, 3 months, and 6 months. Corticosteroid monotherapy was successful in maintaining clinical remission in only one patient, whereas eight out of the ten remaining patients continued to be in remission following the addition of methotrexate.[14] The interpretation of the findings of the study was limited by the small number of patients (although this needs to be understood in the context of TAK being a rare disease), the limited duration of follow-up, the lack of assessment of angiographic evolution of disease following therapy, the lack of evaluation of patient reported outcomes such as quality of life and fatigue, and the lack of a suitable comparator group.[1],[5],[15]

Nevertheless, the present study adds important information from Bangladesh regarding TAK, and the findings are of relevance to the Asian and the South East Asian regions.[16] Clinical trials are difficult in TAK, therefore, good quality observational studies with appropriately matched control groups (matched for key prognostic factors) are essential to better understand the disease.[13] Since clinical response and inflammatory markers have poor concordance with vascular pathology (which itself is difficult to access for evaluation), often a diagnosis of active TAK is only evident retrospectively by the progression of angiographic extent of disease on serial angiography.[5],[6] Emerging modalities like 18-fluorodeoxyglucose positron emission tomography computerized tomography (PET) or PET magnetic resonance imaging hold promise to provide both anatomical and functional information regarding vascular wall metabolic activity.[17] However, PET is not a reliable tool for patients on immunosuppressive therapy.[18] Recent literature has emerged regarding the use of composite scores involving imaging along with serological markers to assess disease activity in TAK. However, such tools require validation across different populations before they can be widely used.[19],[20] Future observational studies should provide due attention to methodological aspects to enhance their quality and contribute valuable scientific information toward the management of TAK.

References

1Misra DP, Wakhlu A, Agarwal V, Danda D. Recent advances in the management of takayasu arteritis. Int J Rheum Dis 2019;22 Suppl 1:60-8.
2Arnaud L, Haroche J, Mathian A, Gorochov G, Amoura Z. Pathogenesis of takayasu's arteritis: A 2011 update. Autoimmun Rev 2011;11:61-7.
3Misra DP, Sharma A, Kadhiravan T, Negi VS. A scoping review of the use of non-biologic disease modifying anti-rheumatic drugs in the management of large vessel vasculitis. Autoimmun Rev 2017;16:179-91.
4Ferfar Y, Mirault T, Desbois AC, Comarmond C, Messas E, Savey L, et al. Biotherapies in large vessel vasculitis. Autoimmun Rev 2016;15:544-51.
5Misra DP, Misra R. Assessment of disease activity in takayasu's arteritis. Indian J Rheumatol 2015;10:S43-7.
6Hoffman GS. Takayasu arteritis: Lessons from the American national institutes of health experience. Int J Cardiol 1996;54 Suppl:S99-102.
7Misra DP, Rathore U, Patro P, Agarwal V, Sharma A. Corticosteroid monotherapy for the management of Takayasu arteritis – A systematic review and meta-analysis. Rheumatol Int 2021;41:1729-42.
8Nakaoka Y, Isobe M, Takei S, Tanaka Y, Ishii T, Yokota S, et al. 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 2018;77:348-54.
9Nakaoka Y, Isobe M, Tanaka Y, Ishii T, Ooka S, Niiro H, et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: Final results of the randomized controlled phase 3 TAKT study. Rheumatology (Oxford) 2020;59:2427-34.
10Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, et al. A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of Takayasu arteritis. Arthritis Rheumatol 2017;69:846-53.
11Rathore U, Thakare DR, Patro P, Agarwal V, Sharma A, Misra DP. A systematic review of clinical and preclinical evidences for Janus kinase inhibitors in large vessel vasculitis. Clin Rheumatol 2021. Online ahead of print [doi: 10.1007/s10067-021-05973-4].
12Rathore U, Patro P, Agarwal V, Sharma A, Misra D. Disease-modifying antirheumatic drugs for the management of takayasu arteritis – Protocol for a systematic review. Indian J Rheumatol 2021;16:79-82.
13Misra DP, Rathore U, Patro P, Agarwal V, Sharma A. Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis – A systematic review and meta-analysis. Clin Rheumatol 2021;40:4391-416.
14Shumy F, Anam AM, Choudhury MR, Shahin A, Haq SA, Rasker JJ, et al. Rate and predictors of response to glucocorticoid therapy in patients of Takayasu arteritis at a tertiary level hospital of Bangladesh: A longitudinal study. Indian J Rheumatol 2021;16:375-80.
15Misra DP, Rathore U, Patro P, Agarwal V, Sharma A. Patient-reported outcome measures in Takayasu arteritis: A systematic review and meta-analysis. Rheumatol Ther 2021;8:1073-93.
16Wong SP, Mok CC, Lau CS, Yip ML, Tam LS, Ying KY, et al. Clinical presentation, treatment and outcome of Takayasu's arteritis in southern Chinese: A multicenter retrospective study. Rheumatol Int 2018;38:2263-70.
17Janes AL, Castro MF, Arraes AE, Savioli B, Sato EI, de Souza AW. A retrospective cohort study to assess PET-CT findings and clinical outcomes in Takayasu arteritis: Does 18F-fluorodeoxyglucose uptake in arteries predict relapses? Rheumatol Int 2020;40:1123-31.
18Mason JC. Takayasu arteritis – Advances in diagnosis and management. Nat Rev Rheumatol 2010;6:406-15.
19Campochiaro C, Misra DP. PET in Takayasu arteritis: Onwards and upwards towards a future of robust multimodality disease activity assessment? Rheumatology (Oxford) 2021. Online ahead of print [doi: 10.1093/rheumatology/keab644].
20Ma LY, Wu B, Jin XJ, Sun Y, Kong XF, Ji ZF, et al. A novel model to assess disease activity in Takayasu arteritis based on 18F-FDG-PET/CT: A Chinese cohort study. Rheumatology (Oxford) 2021. Online ahead of print [doi: 10.1093/rheumatology/keab487].