The common adverse reactions include pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.[5]
In April 2014, siltuximab was approved for medical use in the United States for the treatment of people with multicentric Castleman's disease who do not have human immunodeficiency virus (HIV) or human herpesvirus-8 (HHV-8).[5][6]
Medical uses
Siltuximab is indicated for the treatment of people with multicentric Castleman's disease who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.[2][3]
Side effects
The common adverse reactions include pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.[5]
Drug interactions
Siltuximab may increase CYP450 activity leading to increased metabolism of drugs that are CYP450 substrates.[2]
Mechanism of action
Siltuximab is a chimeric monoclonal antibody that binds to interleukin-6 (IL-6), preventing binding to soluble and membrane bound interleukin-6 receptors. Siltuximab interferes with IL-6 mediated growth of B-lymphocytes and plasma cells, secretion of vascular endothelial growth factor (VEGF) and autoimmune phenomena.[2]
History
Siltuximab demonstrated efficacy and safety in people with idiopathic multicentric Castleman disease.[7][8] Treatment results with siltuximab in B-cell non-Hodgkin's lymphoma are inferior to those obtained in multicentric Castleman disease.[9]
The approval by the US FDA was based on an international, multicenter, randomized (2:1), phase II study comparing every three-week intravenous infusions of siltuximab and best supportive care to placebo and best supportive care.[5] The trial enrolled 79 participants and randomly allocated 53 participants to the siltuximab arm plus best supportive care and 26 participants randomized to the placebo arm plus best supportive care.[5] Siltuximab was administered every three weeks as an intravenous infusion at a dose of 11 mg/kg.[5]
Siltuximab has been evaluated in the treatment of ovarian cancer, however the efficacy for this cancer is debatable.[16] In addition, siltuximab has been evaluated for multiple myeloma, but there was an insignificant increase in response rates.[17]
^ abc"Sylvant EPAR". European Medicines Agency. 30 November 2007. Archived from the original on 24 June 2021. Retrieved 8 June 2024.
^World Health Organization (2009). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 62". WHO Drug Information. 23 (2). hdl:10665/74420.
^Ferrario A, Merli M, Basilico C, Maffioli M, Passamonti F (March 2017). "Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma". Expert Opinion on Investigational Drugs. 26 (3): 367–373. doi:10.1080/13543784.2017.1288213. PMID28140696. S2CID40363229.
^Korneev KV, Atretkhany KN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SA (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis". Cytokine. 89: 127–135. doi:10.1016/j.cyto.2016.01.021. PMID26854213.
^Karkera J, Steiner H, Li W, Skradski V, Moser PL, Riethdorf S, et al. (September 2011). "The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study". The Prostate. 71 (13): 1455–65. doi:10.1002/pros.21362. PMID21321981. S2CID32034042.
^"Siltuximab". ClinicalTrials.gov. Archived from the original on 2 July 2019. Retrieved 20 October 2011.
^van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H, et al. (August 2010). "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease". Journal of Clinical Oncology. 28 (23): 3701–8. doi:10.1200/JCO.2009.27.2377. PMID20625121.
^Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M (2018). "Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities". Current Medicinal Chemistry. 25 (36): 4785–4806. doi:10.2174/0929867324666170712160621. PMID28707587. S2CID30691176.
