Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study

Sota, Jurgen; Vitale, A.; Insalaco, Antonella; Sfriso, Paolo; Lopalco, Giuseppe; Emmi, Giacomo; Cattalini, Marco; Manna, Raffaele; Cimaz, Rolando; Priori, Roberta; Talarico, Rosaria; Marchi, G. De; Frassi, Micol; Gallizzi, Romina; Soriano, Alessandra; Alessio, Maria; Cammelli, Daniele; Maggio, Maria Cristina; Gentileschi, Stefano; Marcolongo, R; Torre, Francesco La; Fabiani, Claudia; Colafrancesco, Serena; Ricci, Francesca; Galozzi, Paola; Viapiana, Ombretta; Verrecchia, Elena; Pardeo, Manuela; Cerrito, Lucia; Cavallaro, Elena; Olivieri, Alma Nunzia; Paolazzi, Giuseppe; Vitiello, Gianfranco; Maier, Armin; Silvestri, Elena; Stagnaro, Chiara; Valesini, Guido; Mosca, Marta; Vita, Salvatore De; Tincani, Anǵela; Lapadula, Giovanni; Frediani, Bruno; Benedetti, Fabrizio; Iannone, Florenzo; Punzi, Leonardo; Salvarani, Carlo; Gargiulo, Mauro; Angotti, Rossella; Messina, Mario; Tosi, Gian Marco; Rigante, Donato; Cantarini, Luca

doi:10.1007/s10067-018-4119-x

Cited by 68 publications

(55 citation statements)

References 27 publications

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“…Several types of agents are available to prevent the biological activtiy of IL-1β, including IL-1β specific antibodies (Canakinumab) [290] and IL1Ra (Anakinra) [290] as well as inflammasome inhibitors (Thalidomide, Parthenolide, and BAY-11-7082) [260,289,291]. The two IL-1 blocking agents Anakinra and Canakinumab have already been approved for the treatment of systemic inflammatory disorders and display an excellent safety profile [290].…”

Section: Inhibition Of Il-1 Signaling Inhibits Tumor Growthmentioning

confidence: 99%

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Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

300

221

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Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1β has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1β generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1β generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1β is a driver of tumor induction and development.

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Section: Inhibition Of Il-1 Signaling Inhibits Tumor Growthmentioning

confidence: 99%

“…The two IL-1 blocking agents Anakinra and Canakinumab have already been approved for the treatment of systemic inflammatory disorders and display an excellent safety profile [290]. …”

Section: Inhibition Of Il-1 Signaling Inhibits Tumor Growthmentioning

confidence: 99%

Interleukin-1 Beta—A Friend or Foe in Malignancies?

Bent

Moll

Grabbe

et al. 2018

IJMS

300

221

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“…The goal of the treatment in AIDs is the remission of the symptoms, the prevention of complications, the normalization of biochemical parameters and a good quality of life. For these reasons, treatment must be started as soon as possible, drugs need to be targeted to the single patient [24] and the therapeutic choose needs the cooperation between the clinicians, the patients and their families. Children need to be considered in the treatment decisions.…”

Section: Discussionmentioning

confidence: 99%

“…The safety profile of Canakinumab is widely documented in paediatric patients [24] and the quality of life improves significantly with a treatment administered monthly with sub cutaneous injections.…”

Section: Discussionmentioning

confidence: 99%

FMF is not always “fever”: from clinical presentation to “treat to target”

Maggio

Corsello

2020

Ital J Pediatr

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Familial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease. Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier. Attacks consist of fever, serositis, arthritis and high levels of inflammatory reactants: C-reactive protein, erythrocyte sedimentation rate, serum amyloid A associated with leucocytosis and neutrophilia. The symptom-free intervals are of different length. The attacks of Familial Mediterranean Fever can have a trigger, as infections, stress, menses, exposure to cold, fatrich food, drugs. The diagnosis needs a clinical definition of the disease and a genetic confirmation. An accurate differential diagnosis is mandatory to exclude infective agents, autoimmune diseases, etc. In many patients there is no genetic confirmation of the disease; furthermore, some subjects with the relieve of MEFV mutations, show a phenotype not in line with the diagnosis of Familial Mediterranean Fever. For these reasons, diagnostic criteria were developed, as Tel Hashomer Hospital criteria, the "Turkish FMF Paediatric criteria", the "clinical classification criteria for autoinflammatory periodic fevers" formulated by PRINTO. The goals of the treatment are: prevention of attacks recurrence, normalization of inflammatory markers, control of subclinical inflammation in attacks-free intervals and prevention of medium and long-term complications, as amyloidosis. Colchicine is the first step in the treatment; biological drugs are effective in non-responder patients. The goal of this paper is to give a wide and broad review to general paediatricians on Familial Mediterranean Fever, with the relative diagnostic, clinical and therapeutic aspects.

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“…An alternative approach to secondary HLH (sHLH) is to target pro‐inflammatory cytokines. Anakinra is a recombinant human IL‐1 receptor antagonist, which competitively inhibits IL‐1α and IL‐1β, with a proven safety record in pediatric patients with sHLH due to autoimmune disorders . Considering its safety profile and therapeutic target, we utilized anakinra in an infant with GS2 to minimize chemotherapy prior to HSCT.…”

mentioning

confidence: 99%