Siltuximab

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.

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

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

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.

Siltuximab demonstrated efficacy and safety in people with idiopathic multicentric Castleman disease.{{cite journal|author-link1=David Fajgenbaum | vauthors = Fajgenbaum DC, Kurzrock R | title = Siltuximab: a targeted therapy for idiopathic multicentric Castleman disease | journal = Immunotherapy | volume = 8 | issue = 1 | pages = 17–26 | date = 2016 | pmid = 26634298 | doi = 10.2217/imt.15.95 }}{{cite journal | vauthors = Sarosiek S, Shah R, Munshi NC | title = Review of siltuximab in the treatment of multicentric Castleman's disease | journal = Therapeutic Advances in Hematology | volume = 7 | issue = 6 | pages = 360–366 | date = December 2016 | pmid = 27904739 | pmc = 5089324 | doi = 10.1177/2040620716653745 }} Treatment results with siltuximab in B-cell non-Hodgkin's lymphoma are inferior to those obtained in multicentric Castleman disease.{{cite journal | vauthors = Ferrario A, Merli M, Basilico C, Maffioli M, Passamonti F | title = Siltuximab and hematologic malignancies. A focus in non Hodgkin lymphoma | journal = Expert Opinion on Investigational Drugs | volume = 26 | issue = 3 | pages = 367–373 | date = March 2017 | pmid = 28140696 | doi = 10.1080/13543784.2017.1288213 | s2cid = 40363229 }}

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. 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. Siltuximab was administered every three weeks as an intravenous infusion at a dose of 11 mg/kg.

Siltuximab has been investigated for the treatment of neoplastic diseases:{{cite journal | vauthors = Korneev KV, Atretkhany KN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SA | title = TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis | journal = Cytokine | volume = 89 | pages = 127–135 | date = January 2017 | pmid = 26854213 | doi = 10.1016/j.cyto.2016.01.021 }} metastatic renal cell cancer,{{cite journal | vauthors = Rossi JF, Négrier S, James ND, Kocak I, Hawkins R, Davis H, Prabhakar U, Qin X, Mulders P, Berns B | title = A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer | journal = British Journal of Cancer | volume = 103 | issue = 8 | pages = 1154–62 | date = October 2010 | pmid = 20808314 | pmc = 2967052 | doi = 10.1038/sj.bjc.6605872 }} prostate cancer,{{cite journal | vauthors = Karkera J, Steiner H, Li W, Skradski V, Moser PL, Riethdorf S, Reddy M, Puchalski T, Safer K, Prabhakar U, Pantel K, Qi M, Culig Z | title = The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study | journal = The Prostate | volume = 71 | issue = 13 | pages = 1455–65 | date = September 2011 | pmid = 21321981 | doi = 10.1002/pros.21362 | s2cid = 32034042 }} other types of cancer,{{cite web |title=Siltuximab |url=http://www.clinicaltrials.gov/ct2/results?term=siltuximab |work=ClinicalTrials.gov |access-date=20 October 2011 |archive-date=2 July 2019 |archive-url=https://web.archive.org/web/20190702163437/http://www.clinicaltrials.gov/ct2/results?term=siltuximab |url-status=live }} and for Castleman's disease.{{cite journal | vauthors = van Rhee F, Fayad L, Voorhees P, Furman R, Lonial S, Borghaei H, Sokol L, Crawford J, Cornfeld M, Qi M, Qin X, Herring J, Casper C, Kurzrock R | title = Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease | journal = Journal of Clinical Oncology | volume = 28 | issue = 23 | pages = 3701–8 | date = August 2010 | pmid = 20625121 | doi = 10.1200/JCO.2009.27.2377 }}{{cite journal | vauthors = Williams SC | title = First IL-6-blocking drug nears approval for rare blood disorder | journal = Nature Medicine | volume = 19 | issue = 10 | pages = 1193 | date = October 2013 | pmid = 24100967 | doi = 10.1038/nm1013-1193 | s2cid = 29140516 | doi-access = free }}

Siltuximab has been evaluated in the treatment of ovarian cancer, however the efficacy for this cancer is debatable.{{cite journal | vauthors = Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M | title = Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities | journal = Current Medicinal Chemistry | volume = 25 | issue = 36 | pages = 4785–4806 | date = 2018 | pmid = 28707587 | doi = 10.2174/0929867324666170712160621 | s2cid = 30691176 }} In addition, siltuximab has been evaluated for multiple myeloma, but there was an insignificant increase in response rates.{{cite journal | vauthors = Naymagon L, Abdul-Hay M | title = Novel agents in the treatment of multiple myeloma: a review about the future | journal = Journal of Hematology & Oncology | volume = 9 | issue = 1 | pages = 52 | date = June 2016 | pmid = 27363832 | pmc = 4929712 | doi = 10.1186/s13045-016-0282-1 | doi-access = free }}

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Category:Monoclonal antibodies

Category:Orphan drugs