Tocilizumab in patients with multisystem Erdheim–Chester disease

Berti, Alvise; Cavalli, Giulio; Guglielmi, B.; Biavasco, Riccardo; Campochiaro, Corrado; Tomelleri, Alessandro; Nicoletti, Roberto; Panzacchi, A.; Ferrarini, Marina; Dagna, Lorenzo

doi:10.1080/2162402x.2017.1318237

Cited by 32 publications

(18 citation statements)

References 21 publications

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“…Clinical manifestations include bone pain, neurological symptoms, retroperitoneal fibrosis, and congestive heart failure ( Cavalli et al, 2013a , b ; Ferrero et al, 2016 ; Iurlo et al, 2016 ; Chiapparini et al, 2018 ). Anakinra is effective in ameliorating skeletal, cardiac, retroperitoneal, and systemic manifestations ( Aouba et al, 2010 ; Killu et al, 2013 ; Franconieri et al, 2016 ; Tomelleri et al, 2018 ), thus substantiating the central role of macrophages in diseases responsive to IL-1 blockade ( Diamond et al, 2014 ; Berti et al, 2017 ; Cavalli et al, 2017a ). Interestingly, a traditional treatment option for ECD, that is, alpha interferon (IFNα), may exert beneficial effects via induction of IL-1Ra ( Tilg et al, 1993 ) and inhibition of inflammasome activation ( Guarda et al, 2011 ).…”

Section: Multifactorial Inflammatory Conditionsmentioning

confidence: 71%

Anakinra Therapy for Non-cancer Inflammatory Diseases

2018

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Interleukin-1 (IL-1) is the prototypical inflammatory cytokine: two distinct ligands (IL-1α and IL-1β) bind the IL-1 type 1 receptor (IL-1R1) and induce a myriad of secondary inflammatory mediators, including prostaglandins, cytokines, and chemokines. IL-1α is constitutively present in endothelial and epithelial cells, whereas IL-1β is inducible in myeloid cells and released following cleavage by caspase-1. Over the past 30 years, IL-1-mediated inflammation has been established in a broad spectrum of diseases, ranging from rare autoinflammatory diseases to common conditions such as gout and rheumatoid arthritis (RA), type 2 diabetes, atherosclerosis, and acute myocardial infarction. Blocking IL-1 entered the clinical arena with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist (IL-1Ra); IL-1Ra prevents the binding of IL-1α as well as IL-1β to IL-1R1. Quenching IL-1-mediated inflammation prevents the detrimental consequences of tissue damage and organ dysfunction. Although anakinra is presently approved for the treatment of RA and cryopyrin-associated periodic syndromes, off-label use of anakinra far exceeds its approved indications. Dosing of 100 mg of anakinra subcutaneously provides clinically evident benefits within days and for some diseases, anakinra has been used daily for over 12 years. Compared to other biologics, anakinra has an unparalleled record of safety: opportunistic infections, particularly Mycobacterium tuberculosis, are rare even in populations at risk for reactivation of latent infections. Because of this excellent safety profile and relative short duration of action, anakinra can also be used as a diagnostic tool for undefined diseases mediated by IL-1. Although anakinra is presently in clinical trials to treat cancer, this review focuses on anakinra treatment of acute as well as chronic inflammatory diseases.

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Section: Multifactorial Inflammatory Conditionsmentioning

confidence: 71%

Anakinra Therapy for Non-cancer Inflammatory Diseases

2018

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“…The first-line treatment of EDC is interferon-α, but high-dose GC and different chemotherapy regimens have also been proposed. Based on increased understanding of EDC pathogenesis, target therapies are being increasingly proposed in the last decade, such as tyrosine kinases inhibitors (TKI) and mAbs including vemurafenib (Allen et al 2018) or tocilizumab blocking the interleukin-6 receptor (Berti et al 2017). An attractive feature of this last drug is its usually good tolerance.…”

Section: Langerhans Cell Histiocytosis (Lch) and Other Histiocytic DImentioning

confidence: 99%

Hypophysitis and Granulomatous Pituitary Lesions in Systemic Diseases

Jaffrain-Rea¹,

Filipponi²

2019

Endocrinology

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In clinical practice, expansive sellar lesions are largely represented by primary diseases of the pituitary gland, mostly pituitary tumors, which can be managed by endocrinologists and/or multidisciplinary pituitary teams. Hypophysitis has long been considered as a rare disease, and is classified on the basis of pathological findings, and as primary or secondary. Nowadays, an enlarging spectrum of pituitary and/or hypothalamic inflammatory, granulomatous, or even neoplastic disorders can be recognized, which may be part of systemic conditions and require appropriate multidisciplinary management involving a variety of specialists. For example, hypophysitis is being increasingly recognized in the setting of systemic IgG4-related disorders or as side effects of immune checkpoints inhibitors in oncological patients. Lymphocytic hypophysitis may sometimes be part of autoimmune polyendocrine syndromes. Significant knowledge has been added in the last decade in the pathogenesis and management of histiocytic disorders, which may infiltrate the pituitary and/or the hypothalamus Infective causes of pituitary inflammation should not be underestimated and are increasingly recognized in immunocompromised patients. Based on updated literature on these topics, this chapter aims to place pituitary inflammatory, granulomatous, and histiocytic disorders in their systemic context and stimulate multidisciplinary collaboration in order to optimize their diagnosis and clinical management.

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“…The last alternative therapeutic strategy involved the use of anti-cytokine agents. The main anti-cytokine therapies that have been investigated in ECD are (1) anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, (2) infliximab, a TNF-α monoclonal chimeric antibody, and (3) tocilizumab, a monoclonal antibody blocking the IL-6 receptor ( 13 , 28 , 29 ). Between these three drugs we chose anakinra, because of its rapid onset of action, excellent safety profile, and—above all—the demonstrated efficacy in the treatment of idiopathic pericarditis, as well as ECD ( 30 , 31 ).…”

Section: Case Reportmentioning

confidence: 99%

“…In particular, activated macrophages produce high amounts of pro-inflammatory cytokines interleukin (IL)-1, IL-6, and TNF-α. Based on this understanding of ECD pathogenesis, different therapeutic approaches have been proposed for the treatment of this disease: first-line treatment with interferon (IFN)-α, treatment with small molecule kinase inhibitors, such as the BRAF inhibitor vemurafenib, and treatment with cytokine-blocking agents ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Treating Heart Inflammation With Interleukin-1 Blockade in a Case of Erdheim–Chester Disease

et al. 2018

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Pericarditis is an inflammatory heart disease, which may be idiopathic or secondary to autoimmune or auto-inflammatory diseases and often leads to severe or life-threatening complications. Colchicine and non-steroidal anti-inflammatory drugs represent the mainstay of treatment, whereas use of corticosteroids is associated with recurrence of disease flares. While effective and safe anti-inflammatory therapies remain an unmet clinical need, emerging clinical and experimental evidence points at a promising role of inhibition of the pro-inflammatory cytokine interleukin-1 (IL-1). We thus evaluated treatment with the IL-1 receptor antagonist anakinra in a case of extremely severe pericarditis with cardiac tamponade and heart failure secondary to Erdheim–Chester disease (ECD), a rare clonal disorder of macrophages characterized by rampant inflammation and multiorgan involvement. A 62-year-old man was admitted to the Emergency Department with severe pericardial effusion requiring the creation of a pleuro-pericardial window. A whole-body contrast-enhanced computed tomography pointed at a diagnosis of ECD with involvement of the heart and pericardium and of the retroperitoneal space. Over the following days, an echocardiography revealed a closure of the pleuro-pericardial window and a relapse of the pericardial effusion. Treatment with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, was started at a standard subcutaneous dose of 100 mg/day. After 2 days, we observed a dramatic clinical improvement, an abrupt reduction of the inflammatory markers, and a reabsorption of the pericardial effusion. Anakinra was maintained as monotherapy, and the patient remained asymptomatic in the absence of disease flares for the following year. Recent studies point at inhibition of IL-1 activity as an attractive treatment option for patients with refractory idiopathic recurrent pericarditis. Anakinra treatment may also have a role in patients with pericarditis in the setting of systemic inflammatory disorders, such as ECD.

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Tocilizumab in patients with multisystem Erdheim–Chester disease

Cited by 32 publications

References 21 publications

Anakinra Therapy for Non-cancer Inflammatory Diseases

Anakinra Therapy for Non-cancer Inflammatory Diseases

Hypophysitis and Granulomatous Pituitary Lesions in Systemic Diseases

Treating Heart Inflammation With Interleukin-1 Blockade in a Case of Erdheim–Chester Disease

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