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etanercept (Enbrel)

Tradename: Enbrel. Biosimilar etanercept-szzs (Erelzi). FDA-approved Aug 2016 [14] Indications: 1) rheumatoid arthritis (RA) a) elevated TNF found in synovial fluid of patients with RA b) may be used in combination with methotrexate [7] 2) psoriatic arthritis 3) ankylosing spondylitis 4) psoriasis (monotherapy) [6,8,10]; 5) Crohn's disease 6) severe congestive heart failure (CHF) - high circulating levels of TNF can cause left ventricular failure in patients with CHF * indications listed in [11] Contraindications: 1) discontinue use of etanercept in patients with serious infections or sepsis 2) do not initiate therapy with etanercept in patients with active infections, including chronic or localized infections* 3) use with caution in patients with diabetes mellitus or other disorders which may predispose patients to infection 4) moderate to severe heart failure 5) concurrent use of other biologic agent (abatacept, rituximab, anakinra, other TNF inhibitor) 6) for now, etanercept should not be offered to patients with Alzheimer's disease [13] * Screening for tuberculosis recommended prior to initiating therapy Pregnancy category: B [11] Dosage: 25 mg SC twice weekly. Each vial of lyophilized Enbrel when reconstituted when 1 mL of bacteriostatic water contains 25 mg of etanercept, 40 mg of mannitol, 10 mg of sucrose & 1.2 mg of tromethamine. Monitor: - screening for tuberculosis [11] - CBC, LFTs, serum creatinine at baseline & every 3-6 month thereafter [11] - annual & as indicated (especially fever) [10] - complete blood count (CBC) - serum C-reactive protein testing - serum ALT & serum GGT - serum glucose Adverse effects: 1) increased risk of infections, including a) sepsis [9] b) upper respiratory tract infections 2) no increased risk of serious infectious when used to treat psoriasis [12] 3) drug-induced lupus erythematosus; increased incidence of autoantibodies a) ANA b) anti ds-DNA c) anti cardiolipin antibodies 4) incidence of malignancy same as expected for RA patients 5) injection site reaction 6) may increase risk of tuberculosis [4,9] 7) worsening of heart failure [5] Mechanism of action: 1) fusion protein consisting of the extracellular ligand-binding portion of TNFRSF1B (two) linked to an immunoglobulin Fc chain - two p75 TNF receptors linked to IgG Fc fragment [11] 2) it binds to & inhibits activity of TNF-alpha & TNF beta? (TNFRSF1B binds TNF-alpha) 3) TNF is implicated as a mediator of synaptic dysfunction in patients with Alzheimer's disease (AD) - excess TNF is present in CSF of AD patients [13] Notes: - high cost $15,000/year (2001)

Related

rheumatoid arthritis (RA)

Specific

Etanercept Parenteral etanercept-szzs (Erelzi)

General

recombinant protein; chimer tumor necrosis factor (TNF) inhibitor

Properties

MISC-INFO: elimination route KIDNEY 1/2life 98-115 HOURS therapeutic-range 1.7-5.6 UG/ML

References

  1. Immunex (Wyeth-Ayerst Laboratories) product information
  2. Journal Watch, Mass Med Soc 20(1):6 (Jan 1) 2000
  3. Enbrel Enrollment Program 888-4Enbrel
  4. Prescriber's Letter 8(10):58 2001
  5. Prescriber's Letter 10(7):39 2003
  6. Journal Watch 24(1):11, 2004 Leonardi CL et al, N Engl J Med 349:2014, 2003 PMID: 14627786
  7. Journal Watch 24(7):58, 2004 Klareskog L et al, Lancet 363:675, 2004 PMID: 15001324
  8. Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R, Cella D, Krishnan R. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006 Jan 7;367(9504):29-35. PMID: 16399150
  9. FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#Enbrel
  10. van Lumig PPM et al Relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab. Br J Dermatol 2011 Mar 24 PMID: 21428975 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2011.10329.x/abstract;jsessionid=A6466AB81A3BD26BF82E78A14E9B7D68.d01t03
  11. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012, 2015, 2018, 2022.
  12. Kalb RE, Fiorentino DF, Lebwohl MG et al Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis: Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol. 2015 May 13 PMID: 25970800
  13. Torro J Is Etanercept Safe and Well Tolerated in Alzheimer Disease? NEJM Journal Watch. May 27, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Butchart J et al. Etanercept in Alzheimer disease: A randomized, placebo- controlled, double-blind, phase 2 trial. Neurology 2015 May 26; 84:2161 PMID: 25934853 http://www.neurology.org/content/84/21/2161
  14. FDA OKs Biosimilar to Etanercept for Inflammatory Diseases. Medscape. Aug 30, 2016. http://www.medscape.com/viewarticle/868196