Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab

Gon, Yoshie; Yoshifuji, Hajime; Nakajima, Toshiki; Murakami, Kosaku; Nakashima, Ran; Ohmura, Koichiro; Mimori, Tsuneyo; Terao, Chikashi

doi:10.1080/14397595.2020.1800560

Cited by 24 publications

(14 citation statements)

References 17 publications

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“…Our case supports the findings of three recently reported cases from Japan, in which ustekinumab was used successfully in refractory Takayasu arthritis disease. In contrast to our patient, those patients did not receive as many prior immunosuppressive therapies, and one had co-existent ulcerative colitis [ 5 , 6 ].…”

contrasting

confidence: 56%

Successful treatment with the IL12/IL23 antagonist ustekinumab in a patient with refractory Takayasu arteritis

Saur¹,

Horger

Henes³

2021

Rheumatology Advances in Practice

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contrasting

confidence: 56%

Successful treatment with the IL12/IL23 antagonist ustekinumab in a patient with refractory Takayasu arteritis

Saur¹,

Horger

Henes³

2021

Rheumatology Advances in Practice

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“…Anti-VEGF antibody, an mTOR inhibitor, and an IL-12/IL-23 inhibitor (e.g., ustekinumab) are on the market. Ustekinumab has been tested for GCA and TAK ( 96 , 97 ), but the results obtained to date are not encouraging ( 98 , 99 ).…”

Section: Discussionmentioning

confidence: 99%

Vasculitogenic T Cells in Large Vessel Vasculitis

Watanabe¹,

Hashimoto²

2022

Front. Immunol.

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Vasculitis is an autoimmune disease of unknown etiology that causes inflammation of the blood vessels. Large vessel vasculitis is classified as either giant cell arteritis (GCA), which occurs exclusively in the elderly, or Takayasu arteritis (TAK), which mainly affects young women. Various cell types are involved in the pathogenesis of large vessel vasculitis. Among these, dendritic cells located between the adventitia and the media initiate the inflammatory cascade as antigen-presenting cells, followed by activation of macrophages and T cells contributing to vessel wall destruction. In both diseases, naive CD4+ T cells are polarized to differentiate into Th1 or Th17 cells, whereas differentiation into regulatory T cells, which suppress vascular inflammation, is inhibited. Skewed T cell differentiation is the result of aberrant intracellular signaling, such as the mechanistic target of rapamycin (mTOR) or the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathways. It has also become clear that tissue niches in the vasculature fuel activated T cells and maintain tissue-resident memory T cells. In this review, we outline the most recent understanding of the pathophysiology of large vessel vasculitis. Then, we provide a summary of skewed T cell differentiation in the vasculature and peripheral blood. Finally, new therapeutic strategies for correcting skewed T cell differentiation as well as aberrant intracellular signaling are discussed.

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“…However, exclusion of individual studies could not ameliorate heterogeneity for pooled estimates of mean prednisolone dose. Separately, Gon et al reported a reduction in mean prednisolone dose by 9.7 mg 1 year following tocilizumab therapy [84]. The pooled proportion of patients experiencing any adverse effect with tocilizumab was 23% (95% CI 12-35%, 13 studies, 162 patients, I 2 53.84%, Supplementary Fig.…”

Section: Biologic Dmardsmentioning

confidence: 97%

Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis—a systematic review and meta-analysis

et al. 2021

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The pharmacotherapy of Takayasu arteritis (TAK) with disease-modifying anti-rheumatic drugs (DMARDs) is an evolving area. A systematic review of Scopus, Web of Science, Pubmed Central, clinical trial databases and recent international rheumatology conferences for interventional and observational studies reporting the effectiveness of DMARDs in TAK identified four randomized controlled trials (RCTs, with another longer-term follow-up of one RCT) and 63 observational studies. The identified trials had some concern or high risk of bias. Most observational studies were downgraded on the Newcastle-Ottawa scale due to lack of appropriate comparator groups. Studies used heterogenous outcomes of clinical responses, angiographic stabilization, normalization of inflammatory markers, reduction in vascular uptake on positron emission tomography, reduction in prednisolone doses and relapses. Tocilizumab showed benefit in a RCT compared to placebo in a secondary per-protocol analysis but not the primary intention-to-treat analysis. Abatacept failed to demonstrate benefit compared to placebo for preventing relapses in another RCT. Pooled data from uncontrolled observational studies demonstrated beneficial clinical responses and angiographic stabilization in nearly 80% patients treated with tumour necrosis factor alpha inhibitors, tocilizumab or leflunomide. Certainty of evidence for outcomes from RCTs ranged from moderate to very low and was low to very low for all observational studies. There is a paucity of high-quality evidence to guide the pharmacotherapy of TAK. Future observational studies should attempt to include appropriate comparator arms. Multicentric, adequately powered RCTs assessing both clinical and angiographic responses are necessary in TAK. Supplementary Information The online version contains supplementary material available at 10.1007/s10067-021-05743-2.

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Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab

Cited by 24 publications

References 17 publications

Successful treatment with the IL12/IL23 antagonist ustekinumab in a patient with refractory Takayasu arteritis

Successful treatment with the IL12/IL23 antagonist ustekinumab in a patient with refractory Takayasu arteritis

Vasculitogenic T Cells in Large Vessel Vasculitis

Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis—a systematic review and meta-analysis

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