| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Chimeric ( mouse/ human) |
| Target | IL-6 |
| Clinical data | |
| Trade names | Sylvant |
| Other names | CNTO 328 |
| License data |
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| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C6450H9932N1688O2016S50 |
| Molar mass | 144983.21 g·mol−1 |
 
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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
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]
Research
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
- ^ "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.
- ^ a b c d e f "Sylvant- siltuximab injection, powder, for solution". DailyMed. 21 February 2024. Retrieved 8 June 2024.
- ^ a b c "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.
- ^
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.
This article incorporates text from this source, which is in the
public domain.
- ^ "Sylvant (siltuximab)". accessdata.fda.gov. 28 September 2015. Archived from the original on 8 February 2024. Retrieved 8 June 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "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. PMID 20625121.
- ^ 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.
- ^ 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.
- ^ 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.
