Zusammenfassung
Mit dem TNF-α-Antagonisten Etanercept steht zur Behandlung der Psoriasisarthritis und der Psoriasis vulgaris ein effektives Medikament zur Verfügung. Etanercept ist ein rekombinant hergestelltes Fusionsprotein, das aus 2 Domänen des p-75-TNF-α-Rezeptors und dem Fc-Fragment des humanen IgG1 besteht. Als Protein ist Etanercept zwingend parenteral (subkutan) zu applizieren. Die Wirksamkeit ist sowohl für die psoriatischen Hautläsionen als auch die Gelenkbeteiligung durch kontrollierte Studien belegt. Die Dosierung beträgt 2-mal 25 mg/Woche, bei schweren Fällen ist eine Dosiserhöhung auf 2-mal 50 mg/Woche möglich. Vor Behandlungsbeginn sind Infektionen einschließlich Tuberkulose auszuschließen. Eine Kombinationsbehandlung mit anderen immunsuppressiven Medikamenten bzw. pharmakologischen Immunmodulatoren ist möglich. Alle topischen Antipsoriatika können ebenfalls mit einer Etanercepttherapie kombiniert werden. Im sog. Off-label-Gebrauch wurde das Fusionsprotein bei einer Reihe weiterer, überwiegend entzündlicher Dermatosen mit Erfolg eingesetzt. Bei richtiger Indikationsstellung, regelrechtem Monitoring und Beobachtung möglicher unerwünschter Wirkungen hat Etanercept ein akzeptables Sicherheitsprofil. Etanercept stellt neben anderen Biologics eine der wichtigsten therapeutischen Innovationen der letzten Jahre dar.
Abstract
Etanercept, an inhibitor of TNF α, has been found effective in the treatment of psoriatic arthritis and psoriasis vulgaris. Etanercept is a fusion protein made up of domains of the soluble, fully human p75-TNF α receptor and the Fc portion of human IgG1. The drug is a protein which must be administered subcutaneously. Several controlled studies have highlighted its efficacy for both skin symptoms and joint involvement. The usual dose is 25 mg s.c. twice weekly. Higher dosages of 50 mg twice weekly may be used in severe cases. Before starting the therapy with etanercept, infections including tuberculosis have to be excluded. Methotrexate and other pharmacological immunosuppressive agents can be combined with etanercept, as can all standard topical agents. Etanercept in off-label use has been found to also be useful in several other inflammatory dermatologic conditions. If patients are carefully monitored, etanercept is generally well-tolerated and has a good safety profile. The development of novel biologic agents such as etanercept is one of the most important therapeutic innovations of recent years.
Notes
Bei einer Grundgesamtheit eines Patientenkollektivs muss sich der Medianwert des PASI nach einem definierten Behandlungszeitraum um mindestens 90% im Vergleich zum Ausgangs-PASI verbessert haben.
Abbreviations
- ACR:
-
American College of Rheumatology
- AE:
-
Adverse Event
- ANA:
-
Antinukleäre Antikörper
- CD:
-
Clusters of differentiation (Nomenklatur der Oberflächenmarker)
- DLQI:
-
Dermatology Life Quality Index (Index für Erfassung der Lebensqualität)
- FDA:
-
Food and Drug Administration (US-amerikanische Zulassungsbehörde)
- GCP:
-
Good Clinical Practice
- HAQ:
-
Health Assessment Questionnaire
- MTX:
-
Methotrexat
- NSAR:
-
Nichtsteroidale Antirheumatika
- PASI:
-
Psoriasis Area and Severity Index
- PGA:
-
Physician Global Assessment
- PsARC:
-
Psoriasis Arthritis Response Criteria
- RA:
-
Rheumatoide Arthritis
- TNF-α:
-
Tumornekrosefaktor-α
- UAW:
-
Unerwünschte Arzneimittelwirkungen
- VAS:
-
Visual Analog Scala (Visuelle Analogskala)
Literatur
Blumberg BS, Bunim JJ, Calkins E et al. (1964) ARA nomenclature and classification of arthritis and rheumatism (tentative). Arthritis Rheum 7:93–97
Bruce IN (2003) Psoriatic arthritis: clinical features. In: Hochberg MC, Silman AJ, Smolen JS et al. (eds) Rheumatology, 3rd edn. Elsevier, London, pp 1241–1252
Chambers C, Johnson D, Jones KL (2005) Safety of anti-TNF-α medications in pregnancy. J Am Acad Dermatol [Suppl] 52:196
Clegg DO, Reda DJ, Mejias E et al. (1996) Comparison of sulfasalazine and placebo in the treatment of psoriasic arthritis. A department of veterans affairs cooperative study. Arthritis Rheum 39:2013–2020
Culy CR, Keating GM (2002) Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis. Drugs 62:2493–2537
AHFS Drug information (2003) Etanercept. American Society of Health-System Pharmacists, Bethesda, pp 3607–3613
Goffe B, Cather JC (2003) Etanercept: an overview. J Am Acad Dermatol 49:S105–S111
Gottlieb AB, Metheson RT, Lowe N et al. (2003) A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 139:1627–1632
Gottlieb AB, Gordon K, Wang A, Zitnik R (2004) Withdrawal from etanercept after successful clinical response in psoriasis patients: disease characteristics and the durability of treatment response. J Am Acad Dermatol 50:P146
Gottlieb AB (2003) Etanercept for treatment of psoriasis and psoriatic arthritis. In: Weinstein GD, Gottlieb AB (eds) Therapy of moderate-to-severe psoriasis, 2nd edn. Dekker, New York Basel, pp 261–283
Holman J, Gardiner M, Wallis WJ et al. (2003) Tuberculosis reports with etanercept (Enbrel) therapy. Ann Rheum Dis 61 [Suppl 1]:167
Iyer S, Yamauchi P, Lowe NJ (2002) Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy. Br J Dermatol 146:118–121
Klareskog L, Moreland LM, Cohen SB et al. (2001) Global safety and efficacy of upto five years of etanercept (Enbrel) therapy. Arthritis Rheum 44 [Suppl]:S77 (Abstract 150)
Kohno T, Stevens S, Louie J, Amgen Inc.,Thousand Oaks, CA, United States (2005) Adalimumab and infliximab bind to Fc-Receptor and C1q and generate immunoprecipitation: a different mechanism from etanercept. J Am Acad Dermatol 52 [Suppl]:36
Leonardi CL, Powers JL, Matheson RT et al. (2003) Etanercept as monotherapy in patients with psoriasis. N Engl J Med 349:2014–2022
Loetscher H, Brockhaus M, Dembic Z et al. (1992) Two distinct human TNF receptors: purification, molecular cloning and expression. In: Osawa T, Bonavida B (eds): Tumor necrosis factor: structure-funcion, relationship and clinical application. Karger, Basel, pp 34–46
Mease PJ, Goffe BS, Metz J et al. (2000) Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomized trial. Lancet 356:385–390
Mease P, Kivitz A, Burch F et al. (2001) Improvement in disease activity in patients with psoriatic arthritis receiving etanercept (ENBREL): results of a phase 3 multicenter clinical trial. Arthritis Rheum 44 [Suppl]:S90–A226
Wyeth (2003) Moderne Rheumatherapie. Patienteninformation. Wyeth Europa Ltd. Berkshire, p 31
Mohler KM, Torrance DS, Smith CA et al. (1993) Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol 151:1548–1561
Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL (2003) Anti-TNF-α therapies: the next generation. Nat Rev Drug Discover 2:736–746
Papp KA, Tyring S, Lahfa M et al. (2005) A global phase III randomized controlled trial of etanercept in psoriasis; safety, efficacy, and effect of dose reduction. Br J Dermatol 152:1304–1312
Peppel K, Crawford D, Beutler B (1991) A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J Exp Med 174:1483–1489
Phillips K, Husni ME, Karlson EW, Coblyn JS (2002) Experience with etanercept in an academic medical center: are infection rates increased? Arthritis Rheum 47:17–21
Rott S, Mrowietz U (2005) Recent developments in the use of biologics in psoriasis and autoimmune disorders. The role of autoantibodies. Br Med J 330:716–720
Sfikakis PP (2002) Behcet’s disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis 61 [Suppl 2]:51–53
Schmitt J, Wozel G (2005) The psoriasis area and severity index is the adequate criterion to define severity in chronic plaque-type psoriasis. Dermatology 210:194–199
Schottelius AJG, Moldawer LL, Dinarello CA et al. (2004) Biology of tumor necrosis factor-α-implications for psoriasis. Exp Dermatol 13:193–222
Shakoor N, Michalska M, Harris CA, Block JA (2002) Drug-induced systemic lupus erythematosus associated with etanercept therapy. Lancet 359:579–580
Stone JH, Uhlfelder ML, Hellmann DB et al. (2001) Etanercept combined with conventional treatment in Wegener’s granulomatosis: a six-months open-label trial to evaluate safety. Arthritis Rheum 44:1149–1154
Weinberg JM (2004) Successful treatment of recalcitrant palmoplantar psoriasis with etanercept. J Am Acad Dermatol 50:P143
Wozel G (Hrsg) (2004) UNI-MED Verlag AG. Bremen London Boston
Wozel G (2005) Clinical review: psoriasis. Recent advances in the treatment of psoriasis. Hospital Pharmacy Europe, London, Sept./Oct. 2005:1–3
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Der korrespondierende Autor weist auf eine Verbindung mit folgender Firma/Firmen hin: Mitglied des Advilon Board von Wyeth Pharma GmbH Deutschland
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Interessenkonflikt: Der Autor ist Mitglied des nationalen Advisory Board von Wyeth Pharma GmbH Deutschland.
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Wozel, G. Etanercept. Hautarzt 56, 819–830 (2005). https://doi.org/10.1007/s00105-005-1006-6
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DOI: https://doi.org/10.1007/s00105-005-1006-6