title: Clinical development of siltuximab.
abstract: Siltuximab is a chimeric monoclonal antibody targeting interleukin-6 (IL-6), which in the fall of 2014 became the first FDA-approved treatment of the rare disease idiopathic multicentric Castleman's disease (MCD). MCD is a non-clonal lymphoproliferative disorder in which common symptoms include fever, night sweats, weight loss, and fatigue. Symptoms are driven by an overall hypercytokinemia, predominantly IL-6. While under clinical development, siltuximab was studied in several other disease states including multiple myeloma, non-Hodgkin lymphomas, and several solid tumors in which it did not demonstrate significant benefit. The efficacy of siltuximab in MCD is mainly confined to systemic symptomatic response and quality of life benefits with minimal complete responses and approximately 30 % partial responses, by radiographic criteria. Siltuximab treatment therefore is important in the overall treatment of this rare disease state. This review focuses on the clinical development and pharmaceutical approval of siltuximab.
authors.affiliation: Department of Pharmaceutical Services, Emory Healthcare, Atlanta, GA, USA, christine.davis@emoryhealthcare.org.
authors.forename: Christine C
authors.initials: CC
authors.lastname: Davis
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Shah
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Lechowicz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005871:Castleman Disease / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017277:Drug Approval; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; C504234:siltuximab