title: Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease.
abstract: Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach.
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy. Electronic address: cantariniluca@hotmail.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinic Hospital, University of Bari, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lopalco
authors.affiliation: Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy; Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caso
authors.affiliation: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Costa
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinic Hospital, University of Bari, Bari, Italy.
authors.forename: Florenzo
authors.initials: F
authors.lastname: Iannone
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinic Hospital, University of Bari, Bari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: Interdisciplinary Department of Medicine, Rheumatology Unit, Policlinic Hospital, University of Bari, Bari, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Anelli
authors.affiliation: Ophthalmology and Neurosurgery Department, University of Siena, Siena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Franceschini
authors.affiliation: Ophthalmology and Neurosurgery Department, University of Siena, Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menicacci
authors.affiliation: Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.affiliation: Division of Rheumatology, Allergy, and Clinical Immunology, University of CA, Davis, USA; Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.affiliation: Institute of Pediatrics, Università Cattolica Sacro Cuore, Rome, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Rigante
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1
keywords: Anakinra; Behçet's disease; Canakinumab; Gevokizumab; Interleukin-1; Tuberculosis