Siltuximab (Sylvant®): A Comprehensive Monograph on the First-in-Class IL-6 Antagonist for Idiopathic Multicentric Castleman's Disease

I. Executive Summary & Introduction

Overview of Siltuximab

Siltuximab is a highly specific, chimeric (human-mouse) immunoglobulin G1-kappa (IgG1κ) monoclonal antibody that functions as a potent antagonist of the cytokine Interleukin-6 (IL-6).[1] Marketed under the brand name Sylvant®, it represents a targeted biologic therapy developed to address diseases driven by the dysregulated overproduction of IL-6.[1] As the first therapeutic agent approved in its class for its primary indication, Siltuximab has established a new standard of care for a specific subset of patients with the rare hematologic disorder, Multicentric Castleman's Disease.[5]

Pathophysiological Context of Multicentric Castleman's Disease (MCD)

Multicentric Castleman's Disease (MCD) is a rare and clinically heterogeneous lymphoproliferative disorder characterized by the systemic overproduction of lymphocytes, leading to pathognomonic enlargement of lymph nodes in multiple anatomical regions.[2] The disease extends beyond simple lymphadenopathy, often affecting lymphoid tissue in visceral organs and causing hepatosplenomegaly.[7] The underlying pathophysiology is driven by a cytokine storm, with dysregulated production of IL-6 identified as the central pathogenic mediator.[2]