title: Biological treatments in Behçet's disease: beyond anti-TNF therapy.
abstract: Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy ; Rheumatology Unit, Department of Medicine DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors: Francesco
authors: 0000-0002-8928-2520
authors: F
authors: Caso
authors: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
authors: Luisa
authors: L
authors: Costa
authors: Institute of Pediatrics, Cattolica Sacro Cuore University, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors: Donato
authors: 0000-0001-7032-7779
authors: D
authors: Rigante
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy.
authors: Orso Maria
authors: 0000-0002-3314-0814
authors: OM
authors: Lucherini
authors: La Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
authors: Paolo
authors: P
authors: Caso
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy.
authors: Vittoria
authors: V
authors: Bascherini
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy.
authors: Bruno
authors: B
authors: Frediani
authors: Department of Pediatrics, Rheumatology Unit, Anna Meyer Children's Hospital and University of Florence, Viale Pieraccini 24, 50139 Florence, Italy.
authors: Rolando
authors: R
authors: Cimaz
authors: Department of Pediatrics, Rheumatology Unit, Anna Meyer Children's Hospital and University of Florence, Viale Pieraccini 24, 50139 Florence, Italy.
authors: Edoardo
authors: 0000-0002-0346-3268
authors: E
authors: Marrani
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy ; Rheumatology Service, Hospital Regional Universitario Carlos Haya, University of Màlaga, Avenida Carlos Haya s/n, 29010 Màlaga, Spain.
authors: Laura
authors: L
authors: Nieves-Martín
authors: Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
authors: Mariangela
authors: M
authors: Atteno
authors: Institute of Pediatrics, Cattolica Sacro Cuore University, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors: Carmela G L
authors: CG
authors: Raffaele
authors: Institute of Pediatrics, Cattolica Sacro Cuore University, Largo Agostino Gemelli 8, 00168 Rome, Italy.
authors: Giusyda
authors: G
authors: Tarantino
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy.
authors: Mauro
authors: M
authors: Galeazzi
authors: Rheumatology Unit, Department of Medicine DIMED, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors: Leonardo
authors: L
authors: Punzi
authors: Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Viale Bracci 1, 53100 Siena, Italy.
authors: Luca
authors: 0000-0002-7352-1275
authors: L
authors: Cantarini
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D000069549:Ustekinumab; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D007375:Interleukin-1; D053583:Interleukin-1beta; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab; D000093242:Interleukin-6 Inhibitors; C541220:canakinumab; C502936:tocilizumab; C547697:gevokizumab