Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS)

Torre, Francesco La; Muratore, Maurizio; Vitale, A.; Moramarco, Fulvio; Quarta, L.; Cantarini, Luca

doi:10.1007/s00296-015-3305-2

Cited by 40 publications

(18 citation statements)

References 36 publications

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“…77 Recent reports of canakinumab use in patients with colchicine-resistant FMF, HIDS, and TRAPS show similar efficacy as observed in those with CAPS. 72,78,79 All 3 of these injectable drugs have similar efficacy in patients with CAPS, which supports the concept that IL-1b is the key driver of disease pathology. Interestingly, milligram/kilogram drug dosing is similar for all 3 compounds; however, the pharmacokinetics differs significantly and require markedly different dosing regimens.…”

Section: Biologic Therapiessupporting

confidence: 60%

The role of the inflammasome in patients with autoinflammatory diseases

Hoffman

Broderick

2016

Journal of Allergy and Clinical Immunology

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Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation often driven by inflammasomes, and independent of infection and autoreactive antibodies or antigen-specific T cells. These diseases are increasingly recognized as disorders of immune dysregulation, presenting with a constellation of fevers, rashes, and mucosal symptoms in many cases, which suggests that the allergist/immunologist is the appropriate specialist for these patients. However, many practicing physicians are unaware of these disorders in their pediatric and adult patient populations, leading to substantial delays in diagnosis. Recognizing autoinflammatory disease symptom patterns, performing appropriate diagnostic tests, and instituting early effective therapy are essential to reduce morbidity and mortality in these patients. This review will focus on understanding the molecular basis of inflammasomes, recognizing the distinguishing features of the classic autoinflammatory disorders, and appreciating the treatment modalities available.

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Section: Biologic Therapiessupporting

confidence: 60%

The role of the inflammasome in patients with autoinflammatory diseases

Hoffman

Broderick

2016

Journal of Allergy and Clinical Immunology

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“…1k). These findings support and extend previous studies [14][15][16][17] by revealing the presence of additional proinflammatory serum cytokines/chemokines (IFN-γ, IL-17, IL-22 and MCP-1) in TRAPS patients and also increased serum TGF-β and VEGF.…”

Section: In-vivo Constitutive Inflammatory Stimulation In Traps Patientssupporting

confidence: 91%

Patients with tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are hypersensitive to Toll-like receptor 9 stimulation

Negm

Singh

Abduljabbar

et al. 2019

Clinical and Experimental Immunology

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Summary Tumour necrosis factor receptor‐associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder characterized by recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNFRSF1A, which encodes tumour necrosis factor receptor 1 (TNF‐R1). Our aim was to understand the influence of TRAPS mutations on the response to stimulation of the pattern recognition Toll‐like receptor (TLR)‐9. Peripheral blood mononuclear cells (PBMCs) and serum were isolated from TRAPS patients and healthy controls: serum levels of 15 proinflammatory cytokines were measured to assess the initial inflammatory status. Interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17, IL‐22, tumour necrosis factor (TNF)‐α, vascular endothelial growth factor (VEGF), interferon (IFN)‐γ, monocyte chemoattractant protein 1 (MCP‐1) and transforming growth factor (TGF)‐β were significantly elevated in TRAPS patients’ sera, consistent with constitutive inflammation. Stimulation of PBMCs with TLR‐9 ligand (ODN2006) triggered significantly greater up‐regulation of proinflammatory signalling intermediates [TNF receptor‐associated factor (TRAF 3), IL‐1 receptor‐associated kinase‐like 2 (IRAK2), Toll interacting protein (TOLLIP), TRAF6, phosphorylated transforming growth factor‐β‐activated kinase 1 (pTAK), transforming growth factor‐β‐activated kinase‐binding protein 2 (TAB2), phosphorylated TAK 2 (pTAB2), IFN‐regulatory factor 7 (IRF7), receptor interacting protein (RIP), nuclear factor kappa B (NF‐κB) p65, phosphorylated NF‐κB p65 (pNF‐κB p65) and mitogen‐activated protein kinase kinase (MEK1/2)] in TRAPS patients’ PBMCs. This up‐regulation of proinflammatory signalling intermediates and raised serum cytokines occurred despite concurrent anakinra treatment and no overt clinical symptoms at time of sampling. These novel findings further demonstrate the wide‐ranging nature of the dysregulation of innate immune responses underlying the pathology of TRAPS and highlights the need for novel pathway‐specific therapeutic treatments for this disease.

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“…It is characterized by recurrent and prolonged fever, myalgia, arthralgia, erysipelas, and serositis. A 4-year-old boy diagnosed with TRAPS related to a heterozygous variant in the TNFRSF1A gene had already received glucocorticoids, anti-IL-1β monoclonal antibody, TNF inhibitor (infliximab), and tocilizumab based on a previous diagnosis of systemic JIA [75]. After the DNA mutation was identified, he received a tocilizumab infusion, which resulted in the sustained remission of all symptoms for at least 2 years.…”

Section: Resultsmentioning

confidence: 99%

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review

et al. 2018

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Tocilizumab, an anti-interleukin-6 (IL-6) agent, is indicated as a treatment for several autoimmune or inflammatory diseases, including rheumatoid arthritis and juvenile idiopathic arthritis (JIA). IL-6 plays roles in both immune system dysregulation and inflammation, and thus efforts to extend the utility of tocilizumab in patients with autoinflammatory conditions are ongoing. Here, we survey the literature on the off-label use of tocilizumab in patients with juvenile-onset rheumatic diseases including juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis (DM), vasculitis, juvenile scleroderma, and other autoinflammatory diseases. There is no real evidence that tocilizumab is useful for patients with SLE and juvenile DM, but several cases of childhood Takayasu arteritis have experienced promising outcomes. In juvenile-onset scleroderma, for which no therapy that can halt disease progression is available, tocilizumab may stop progression and the associated functional impairment. Tocilizumab prevents systemic inflammation in patients with Kawasaki’s disease, but may develop coronary aneurysms. Tocilizumab has been used to treat several pediatric autoinflammatory diseases, including JIA-associated uveitis and Castleman’s disease. Further work in larger populations is necessary to confirm the effects of tocilizumab in patients with pediatric rheumatic diseases.

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Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS)

Cited by 40 publications

References 36 publications

The role of the inflammasome in patients with autoinflammatory diseases

The role of the inflammasome in patients with autoinflammatory diseases

Patients with tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are hypersensitive to Toll-like receptor 9 stimulation

Off-label use of tocilizumab to treat non-juvenile idiopathic arthritis in pediatric rheumatic patients: a literature review

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