Etanercept

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Etanercept
Etanercept
Schematic representation
Identifier
External IDs
Drug information
ATC code L04 AB01
DrugBank DB00005
Drug class Immunosuppressants

Etanercept is a drug that is used to treat rheumatic diseases and psoriasis . It is a genetically engineered protein that binds inflammation- inducing cytokines and thus inactivates them. Etanercept was originally developed by Immunex, which company was bought by Amgen . In Germany, Austria and Switzerland, Etanercept is sold by the pharmaceutical company Pfizer under the brand name Enbrel ® and is subject to medical prescription . Samsung Bioepis received approval for its biosimilar Benepali ® for Etanercept in Europe in early 2016 .

structure

Etanercept is a genetically engineered fusion protein that is produced in Chinese hamster ovarian cell lines ( CHO cells ). It is a dimeric chimeric protein that consists of the extracellular ligand binding domain of the human tumor necrosis factor receptor 2 (TNFR2 / p75) linked to the F c subunit of the human IgG1 antibody . Etanercept consists of 934 amino acids and has a molecular mass of about 150 kDa. Etanercept is a complex molecule with 6 N-glycans, up to 14 O-glycans and 29 disulfide bridges.

pharmacology

Mechanism of action

Etanercept possesses the ligand binding domain of the human tumor necrosis factor receptor 2. Thanks to this ligand binding domain it is able to bind the proinflammatory cytokine tumor necrosis factor (TNFα) and lymphotoxin (TNFβ). Tumor necrosis factor and lymphotoxin are proinflammatory cytokines that bind to two different cellular receptors: the p55 and p75 tumor necrosis factor receptors (TNFR). The tumor necrosis factor bound by Etanercept can no longer bind to its natural receptor located on the cell membrane and thus cannot trigger any inflammatory processes . There is a balance (competition) between the binding of the tumor necrosis factor to etanercept and the receptor.

TNF antibodies and latent tuberculosis or toxoplasmosis

Since Etanercerpt influences immune reactions and, among other things, can flare up again during treatment, latent tuberculosis, treatment must be preceded by a test for TB, which must be negative. The same applies to latent toxoplasmosis (which also has a high prevalence in all western European countries).

Crohn's disease

When using Etanercept, especially in patients with ankylosing spondylitis , the occurrence of new chronic inflammatory bowel diseases and v. a. of Crohn's disease was observed, with an incidence of 0.8 per hundred patient-years (and 0.5 under placebo), although if the number of cases was insufficient, no significance and no correlation could be established.

Trade name

Enbrel (Pfizer)

Biosimilars :

Erelzi ( Sandoz / Hexal - EU since 2018) Benepali (Biogen- EU since 2018)

Web links

literature

Individual evidence

  1. RL Yung: Etanercept Immunex. In: Current opinion in investigational drugs (London, England: 2000). Volume 2, Number 2, February 2001, pp. 216-221, PMID 11816834 (review).
  2. ^ Amgen acquires Immunex in a $ 16 billion deal, adding Enbrel to its blockbuster drug portfolio. PubMed, accessed July 9, 2014 .
  3. Red List online, as of September 2009.
  4. AM comp. d. Switzerland, as of September 2009.
  5. AGES-PharmMed, as of September 2009.
  6. BUSINESS WIRE: Samsung Bioepis enters the European biopharmaceutical market with Benepali® - the first fusion protein biosimuar (sic!) Approved by the EU Commission. Financial meeting, archived from the original on February 10, 2016 ; accessed on February 10, 2016 .
  7. Information for professionals Enbrel ® 25 mg / 50 mg.
  8. Yohei Mukai, Teruya Nakamura, Mai Yoshikawa, Yasuo Yoshioka, Shin-ichi Tsunoda: Solution of the structure of the TNF-TNFR2 complex . In: Science Signaling . tape 3 , no. 148 , November 16, 2010, p. ra83 , doi : 10.1126 / scisignal.2000954 , PMID 21081755 .
  9. Stephane Houel, Mark Hilliard, Ying Qing Yu, Niaobh McLoughlin, Silvia Millan Martin: N- and O-glycosylation analysis of etanercept using liquid chromatography and quadrupole time-of-flight mass spectrometry equipped with electron-transfer dissociation functionality . In: Analytical Chemistry . tape 86 , no. 1 , January 7, 2014, p. 576-584 , doi : 10.1021 / ac402726h , PMID 24308717 .
  10. ^ William C. Lamanna, Robert Ernst Mayer, Alfred Rupprechter, Michael Fuchs, Fabian Higel: The structure-function relationship of disulfide bonds in etanercept . In: Scientific Reports . tape 7 , no. 1 , June 21, 2017, p. 3951 , doi : 10.1038 / s41598-017-04320-5 , PMID 28638112 , PMC 5479810 (free full text).
  11. Gardam MA, Keystone EC, Menzies R, et al. : Anti-tumor necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management . In: Lancet Infect Dis . 3, No. 3, March 2003, pp. 148-55. PMID 12614731 .
  12. Keane J, Gershon S, Wise RP, et al. : Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent . In: N. Engl. J. Med. . 345, No. 15, October 2001, pp. 1098-1104. PMID 11596589 .
  13. Mohan AK, Coté TR, Block JA, Manadan AM, Siegel JN, Braun MM: Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor . In: Clin. Infect. Dis. . 39, No. 3, August 2004, pp. 295-299. doi : 10.1086 / 421494 . PMID 15306993 .
  14. Nagwa Mostafa El-Sayed, Khadiga Ahmed Ismail, Abeer Fathy Badawy, Khaled Fathy Elhasanein: In vivo effect of anti-TNF agent (etanercept) in reactivation of latent toxoplasmosis . In: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology . tape 40 , no. 4 , December 2016, ISSN  0971-7196 , p. 1459-1465 , doi : 10.1007 / s12639-015-0712-y , PMID 27876967 , PMC 5118338 (free full text).
  15. Jing Yang, Luyao Wang, Dongmei Xu, Ding Tang, Senyang Li: Risk Assessment of Etanercept in Mice Chronically Infected With Toxoplasma gondii . In: Frontiers in Microbiology . tape 9 , 2018, ISSN  1664-302X , p. 2822 , doi : 10.3389 / fmicb.2018.02822 , PMID 30519229 , PMC 6258779 (free full text).
  16. Bénédicte De Vroey, Michael Schapira, Jean-Michel Ghilain: A Terminal Event New England Journal of Medicine 2019, Volume 381, Issue 22 of November 28, 2019, page 2183, DOI: 10.1056 / NEJMc1913325
  17. Pharmacy Adhoc: Erelzi: Enbrel Hexal . In: APOTHEKE ADHOC . ( apotheke-adhoc.de [accessed on November 26, 2018]).