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Siltuximab

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Siltuximab
Monoclonal antibody
TypeWhole antibody
SourceChimeric (mouse/human)
TargetIL-6
Clinical data
Trade namesSylvant
Other namesCNTO 328
License data
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6450H9932N1688O2016S50
Molar mass144983.21 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Siltuximab (INN[4]), sold under the brand name Sylvant, is used for the treatment of people with multicentric Castleman's disease.[2][3] It is a chimeric (made from human and mouse proteins) monoclonal antibody that binds to interleukin-6. It is an interleukin-6 (IL-6) antagonist.[2]

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

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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

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The common adverse reactions include pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.[5]

Drug interactions

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Siltuximab may increase CYP450 activity leading to increased metabolism of drugs that are CYP450 substrates.[2]

Mechanism of action

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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

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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]

Research

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Siltuximab has been investigated for the treatment of neoplastic diseases:[10] metastatic renal cell cancer,[11] prostate cancer,[12] other types of cancer,[13] and for Castleman's disease.[14][15]

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]

References

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  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  2. ^ a b c d e f "Sylvant- siltuximab injection, powder, for solution". DailyMed. 21 February 2024. Retrieved 8 June 2024.
  3. ^ a b c "Sylvant EPAR". European Medicines Agency. 30 November 2007. Archived from the original on 24 June 2021. Retrieved 8 June 2024.
  4. ^ World Health Organization (2009). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 62". WHO Drug Information. 23 (2). hdl:10665/74420.
  5. ^ a b c d e f "Siltuximab". U.S. Food and Drug Administration (FDA). 23 April 2014. Archived from the original on 3 June 2014. Public Domain This article incorporates text from this source, which is in the public domain.
  6. ^ "Sylvant (siltuximab)". accessdata.fda.gov. 28 September 2015. Archived from the original on 8 February 2024. Retrieved 8 June 2024.
  7. ^ Fajgenbaum DC, Kurzrock R (2016). "Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease". Immunotherapy. 8 (1): 17–26. doi:10.2217/imt.15.95. PMID 26634298.
  8. ^ Sarosiek S, Shah R, Munshi NC (December 2016). "Review of siltuximab in the treatment of multicentric Castleman's disease". Therapeutic Advances in Hematology. 7 (6): 360–366. doi:10.1177/2040620716653745. PMC 5089324. PMID 27904739.
  9. ^ 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. PMID 28140696. S2CID 40363229.
  10. ^ 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. PMID 26854213.
  11. ^ Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, et al. (October 2010). "A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer". British Journal of Cancer. 103 (8): 1154–62. doi:10.1038/sj.bjc.6605872. PMC 2967052. PMID 20808314.
  12. ^ 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. PMID 21321981. S2CID 32034042.
  13. ^ "Siltuximab". ClinicalTrials.gov. Archived from the original on 2 July 2019. Retrieved 20 October 2011.
  14. ^ 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. PMID 20625121.
  15. ^ Williams SC (October 2013). "First IL-6-blocking drug nears approval for rare blood disorder". Nature Medicine. 19 (10): 1193. doi:10.1038/nm1013-1193. PMID 24100967. S2CID 29140516.
  16. ^ 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. PMID 28707587. S2CID 30691176.
  17. ^ Naymagon L, Abdul-Hay M (June 2016). "Novel agents in the treatment of multiple myeloma: a review about the future". Journal of Hematology & Oncology. 9 (1): 52. doi:10.1186/s13045-016-0282-1. PMC 4929712. PMID 27363832.
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