Siltuximab

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Siltuximab
Monoclonal antibody
TypeWhole antibody
SourceChimeric (mouse/human)
TargetIL-6
Names
Trade namesSylvant
Other namesCNTO 328
Clinical data
Drug classMonoclonal antibody[1]
Main usesMulticentric Castleman’s disease (MCD)[2]
Side effectsRash, itchiness, weight gain, swelling, low platelets, upper respiratory infections[3]
Pregnancy
category
  • US: C (Risk not ruled out)
Legal
License data
Legal status
Chemical and physical data
FormulaC6450H9932N1688O2016S50
Molar mass144983.21 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Siltuximab, sold under the brand name Sylvant, is a medication used to treat multicentric Castleman’s disease (MCD) in those who have neither HIV nor human herpesvirus-8 (HHV-8).[2] It is given by gradual injection into a vein.[2]

Common side effects include rash, itchiness, weight gain, swelling, low platelets, and upper respiratory infections.[3] Other side effects may include anaphylaxis and gastrointestinal perforation.[3] It is a monoclonal antibody which binds to interleukin 6 (IL-6) thus blocking its activity.[1]

Siltuximab was approved for medical use in the United States and Europe in 2014.[3][1] In the United Kingdom it costs the NHS about £1,700 per 400 mg vial as of 2021.[2] This amount in the United States costs about 5,200 USD.[4]

Medical uses

Used for the treatment of idiopathic multicentric Castleman disease (iMCD).[5]

Dosage

It is given at a dose of 11 mg/kg every three weeks.[2]

Side effects

Siltuximab may lower resistance to infections and should not be administered to patients with severe infections. Siltuximab should be discontinued in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions or cytokine release syndromes. Live vaccines should not be administered to patients receiving siltuximab since IL-6 inhibition may interfere with normal immune response to new antigens.[5]

Common The following has been shown to occur in treatment of Multicentric Castleman's disease with siltuximab during a clinical trial (>10% compared to placebo):[5]

Long term exposure

Interactions

Siltuximab may increase CYP450 activity leading to increased metabolism of drugs that are CYP450 substrates. Co-administration of siltuximab and CYP450 substrates with narrow therapeutic index such as warfarin, ciclosporin or theophylline should be closely monitored.[5]

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.[5]

Research

Siltuximab has demonstrated significant efficacy and safety in patients with idiopathic multicentric Castleman disease.[6][7] Treatment results with Siltuximab in B-cell non-Hodgkin's lymphoma are inferior to those obtained in multicentric Castleman disease.[8] Siltuximab has also been evaluated in the treatment ovarian cancer, however the efficacy for this cancer is debatable.[9] In addition, siltuximab has been evaluated for multiple myeloma, but there was an insignificant increase in response rates.[10]

References

  1. 1.0 1.1 1.2 "Sylvant". Retrieved 12 October 2021.
  2. 2.0 2.1 2.2 2.3 2.4 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 935. ISBN 978-0-85711-369-6.CS1 maint: date format (link)
  3. 3.0 3.1 3.2 3.3 "Siltuximab Monograph for Professionals". Drugs.com. Retrieved 12 October 2021.
  4. "Sylvant Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 12 October 2021.
  5. 5.0 5.1 5.2 5.3 5.4 "Sylvant Prescribing Information" (PDF). janssenmd. Retrieved 3 November 2014.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.

External links

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