Corticosteroid- and cyclophosphamide-free treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis using tocilizumab

Sakai, Ryota; Shibata, Akiko; Chino, Kentaro; Kondo, Tsuneo; Okuyama, Atsushi; Takei, Hiroyuki; Amano, Koichi

doi:10.3109/14397595.2015.1021138

Cited by 9 publications

(5 citation statements)

References 7 publications

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“…Additionally, another literature review assessed the effectiveness and safety of tocilizumab in this population when combined with large-dose CS and reported its potential for treating primary and secondary vasculitis[ 8 ]. There was also a case of MPA that was successfully treated with tocilizumab alone[ 9 ]. Nevertheless, whether tocilizumab is still active in EGPA remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Tang¹,

Xu²,

Hong³

et al. 2023

World J Clin Cases

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BACKGROUND Tocilizumab is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vasculitis. However, tocilizumab in combination with glucocorticoids for successfully treating granulomatosis with polyangiitis (GPA) has rarely been reported. CASE SUMMARY Here, we report a 40-year-old male patient who suffered GPA for 4 years. He was treated with multiple rounds of drugs, including cyclophosphamide, Tripterygium wilfordii, mycophenolate mofetil, and belimumab, with no improvement. In addition, he exhibited persistently high IL-6 levels. After tocilizumab treatment, his symptoms improved, and his inflammatory marker levels returned to normal. CONCLUSION Tocilizumab may be effective for treating GPA.

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Section: Discussionmentioning

confidence: 99%

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Tang¹,

Xu²,

Hong³

et al. 2023

World J Clin Cases

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“…Sakai et al [42] also reported a case involving AAV that developed in a 69-year-old man being treated with bucillamine for rheumatoid arthritis. The AAV was accompanied by interstitial pneumonia, pauci-immune and crescent-forming glomerulonephritis, and mononeuritis multiplex.…”

Section: Interleukin-6 Targeted Therapymentioning

confidence: 99%

“…Sakai et al [42] conducted an open-label pilot study of tocilizumab for MPA. Patients with newly developed MPA classified according to the algorithm of the European Medical Agency [43] were eligible for the study.…”

Section: Interleukin-6 Targeted Therapymentioning

confidence: 99%

Molecular targeted therapies for microscopic polyangiitis and granulomatosis with polyangiitis

Harigai

Tsutsumino

Takada

et al. 2019

Korean J Intern Med

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Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.

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“…[1][2][3] Moreover, we and others have recently reported that TCZ is an effective treatment in some patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). [4][5][6][7] Although IL-6 plays an important role in the pathogenesis of many autoimmune diseases, the mechanism of TCZ efficacy remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…With the introduction of biologics to rheumatoid arthritis, tocilizumab (TCZ), a humanised anti‐interleukin (IL)‐6 receptor (IL‐6R) monoclonal antibody, is a promising agent in various autoimmune diseases, such as large vessel vasculitis (giant cell arteritis and Takayasu arteritis) and adult‐onset Still's disease 1–3 . Moreover, we and others have recently reported that TCZ is an effective treatment in some patients with anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) 4–7 . Although IL‐6 plays an important role in the pathogenesis of many autoimmune diseases, the mechanism of TCZ efficacy remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab monotherapy uncovered the role of the CCL22/17‐CCR4⁺ Treg axis during remission of crescentic glomerulonephritis

et al. 2020

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Objectives Tocilizumab (TCZ) is a humanised anti‐interleukin (IL)‐6 receptor (IL‐6R) monoclonal antibody that is a promising agent to treat various autoimmune diseases. However, the mechanism of TCZ efficacy is unclear. This study aims to elucidate the relationship between Tregs and IL‐6R blockade in autoimmunity‐mediated renal disease based on a TCZ‐treated cohort of patients with anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) and in an experimental model of crescentic glomerulonephritis (cGN). Methods We examined multiple serum levels of cytokines and chemokines and peripheral blood mononuclear cells in patients with AAV who received TCZ monotherapy and achieved drug‐free remission. Moreover, we investigated the mechanistic role of IL‐6R blockade in accelerated cGN model to analyse the local sites of inflammation. Results Serum chemokines CCL22 and CCL17, in addition to the CCR4 + Foxp3 + Treg population, increased in patients who demonstrated drug‐free remission after the cessation of TCZ. In the cGN model, IL‐6R blockade ameliorated the disease, elevated CCL22/17 in CD206 + CD11b + CD11c + kidney M2‐like type macrophages, and increased the migration of Tregs into the kidney and regional lymph nodes. The local administration of CCL22 in the kidney facilitated Treg accumulation and reduced glomerular crescent formation. Conclusions This study revealed a new mechanism whereby effector Tregs migrate into the inflammatory kidney via the CCL22/17–CCR4 axis that is facilitated by M2‐like type macrophages that are induced by IL‐6R blockade.

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Corticosteroid- and cyclophosphamide-free treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis using tocilizumab

Cited by 9 publications

References 7 publications

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Molecular targeted therapies for microscopic polyangiitis and granulomatosis with polyangiitis

Tocilizumab monotherapy uncovered the role of the CCL22/17‐CCR4⁺ Treg axis during remission of crescentic glomerulonephritis

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Corticosteroid- and cyclophosphamide-free treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis using tocilizumab

Cited by 9 publications

References 7 publications

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids: A case report

Molecular targeted therapies for microscopic polyangiitis and granulomatosis with polyangiitis

Tocilizumab monotherapy uncovered the role of the CCL22/17‐CCR4+ Treg axis during remission of crescentic glomerulonephritis

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Tocilizumab monotherapy uncovered the role of the CCL22/17‐CCR4⁺ Treg axis during remission of crescentic glomerulonephritis