Aktuelle Dermatologie 2003; 29(8/09): 341-346
DOI: 10.1055/s-2003-41986
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Systemische Immunsuppressiva in der Therapie der Psoriasis

Systemic Immunosuppressive Drugs in the Treatment of PsoriasisC.  C.  Geilen1
  • 1Klinik und Poliklinik für Dermatologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin
Further Information

Publication History

Publication Date:
16 September 2003 (online)

Zusammenfassung

Immunsuppressiva wirken auf einen Schenkel der psoriatischen Pathogenese, dem aktivierten Immunsystem. Hierbei lassen sich aufgrund ihres Wirkungsprinzips fünf therapeutische Ansatzpunkte erkennen: (i) Hemmung der Effektorzytokine, (ii) Hemmung der T-Zellproliferation, (iii) Hemmung der T-Zellaktivierung, (iv) Hemmung der T-Zellmigration und (v) Modulation der Immunantwort. Die Entwicklung systemischer Immunsuppressiva hat nicht nur das Spektrum der Psoriasistherapie maßgeblich erweitert, sondern hat auch einen profunden Beitrag zum Verständnis der Pathogenese der Psoriasis geleistet. Sie sind sehr wirksam in der Vermeidung von Transplantatabstossungsreaktionen. Betrachtet man ihr Wirkungs-Nebenwirkungs-Verhältnis hinsichtlich der Behandlung einer benignen chronischen Dermatose, wie der Psoriasis, so muss eine kritische Abwägung bezüglich ihres Einsatzes vorgenommen werden. Systemische Immunsuppressiva müssen demnach schweren, therapierefraktären Fällen der Psoriasis vorbehalten bleiben.

Abstract

Immunosuppressive drugs act on one part of the psoriatic pathogenesis, the activated immune system. Different therapeutical strategies can be considered on the background of their molecular mechanisms therefore of action: (i) inhibition of effector cytokines, (ii) inhibition of T-cell proliferation, (iii) inhibition of T-cell activation, (iv) inhibition of T-cell migration and (v) modulation of the immunoreaction. On the one hand the development of systemic immunosuppressive drugs has enlarged our therapeutical possibilities in psoriasis. On the other hand these substances increased our understanding of the molecular pathways involved in the pathogenesis of psoriasis. Immunosuppressive drugs are highly potent in avoiding graft reactions, but in therapy of a benign, chronic dermatosis like psoriasis it should be considered that these compounds are also associated with significant cutaneous and/or systemic adverse effects and the risk/benefit ratio must be taken into account. Systemic immunosuppressive drugs are therefore limited to patients with a severe psoriasis refractory to other therapies.

Literatur

  • 1 Christophers E. The immunopathology of psoriasis.  Int Arch Allergy Immunol. 1996;  110 199-206
  • 2 Geilen C C, Orfanos C E. Standard and innovative therapy of psoriasis.  Clin Exp Rheumatol. 2002;  20 (Suppl 28) 81-87
  • 3 Ellis C N, Krueger G G. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes.  N Engl J Med. 2001;  345 248-255
  • 4 Krueger J G. The immunologic basis for the treatment of psoriasis with new biologic agents.  J Am Acad Dermatol. 2002;  46 1-23
  • 5 Müller W, Herrmann B. Cyclosporine A for psoriasis.  N Engl J Med. 1979;  301 555
  • 6 Berth-Jones J, Voorhees J J. Consensus conference on cyclosporin A microemulsion for psoriasis.  Br J Dermatol. 1996;  135 775-777
  • 7 Mrowietz U, Färber L, Henneicke von Zepelin H H, Bachmann H, Welzel D, Christophers E. Long-term maintenance therapy with cyclosporine and post-treatment survey in severe psoriasis, results of a multicenter study.  J Am Acad Dermatol. 1995;  33 470-475
  • 8 Al-Daraji W I, Grant K R, Ryan K, Saxton A, Reynolds N J. Localization of calcineurin/NFAT in human skin and psoriasis and inhibition of calcineurin/NFAT activation in human keratinocytes by cyclosporin A.  J Invest Dermatol. 2002;  118 779-788
  • 9 The European FK 506 Multicentre Psoriasis Study Group. Systemic tacrolimus (FK 506) is effective for the treatment of psoriasis in a double-blind, placebo-controlled study.  Arch Dermatol. 1996;  132 419-423
  • 10 Oh C J, Das K M, Gottlieb A B. Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions.  J Am Acad Dermatol. 2000;  42 829-830
  • 11 Chaudhari U, Romano P, Mulcahy L D, Dooley L T, Baker D G, Gottlieb A B. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial.  Lancet. 2001;  357 1842-1847
  • 12 Kirby B, Marsland A M, Carmichael A J, Griffiths C E. Successful treatment of severe recalcitrant psoriasis with combination infliximab and methotrexate.  Clin Exp Dermatol. 2001;  26 27-29
  • 13 Nunez Martinez O, Ripoll Noiseux C, Carneros Martin J A, Gonzales Lara V, Gregorio Maranon H G. Reactivation tuberculosis in a patient with anti-TNF-alpha treatment.  Am J Gastroentererol. 2001;  96 1665-1666
  • 14 Mease P J, Goffe B S, Metz J, VanderStoep A, Finck B, Burge D J. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial.  Lancet. 2000;  356 385-390
  • 15 Yazici Y, Erkan D, Lockshin M D. A preliminary study of etanercept in the treatment of severe, resistant psoriatic arthritis.  Clin Exp Rheumatol. 2000;  18 732-734
  • 16 Iyer S, Yamauchi P, Lowe N J. Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy.  Br J Dermatol. 2002;  146 118-121
  • 17 Huang S, Mills L, Mian B, Tellez C, McCarty M, Yang X D, Gudas J M, Bar-Eli M. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma.  Am J Pathol. 2002;  161 125-134
  • 18 Roenigk H H , Auerbach R, Maibach H, Weinstein G, Lebwohl M. Methotrexate in psoriasis: consensus conference.  J Am Acad Dermatol. 1998;  38 478-485
  • 19 Kuijpers A L, van de Kerkhof P C. Risk-benefit assessment of methotrexate in the treatment of severe psoriasis.  Am J Clin Dermatol. 2000;  1 27-39
  • 20 Geilen C C, Tebbe B, Bartels C G, Krengel S, Orfanos C E. Successful treatment of erythrodermic psoriasis with mycophenolate mofetil.  Br J Dermatol. 1998;  138 1101-1102
  • 21 Haufs M G, Beissert S, Grabbe S, Schütte B, Luger T A. Psoriasis vulgaris treated successfully with mycophenolate mofetil.  Br J Dermatol. 1998;  138 179-181
  • 22 Geilen C C, Arnold M, Orfanos C E. Mycophenolate mofetil as a systemic antipsoriatic agent: Positive experience in 11 patients.  Br J Dermatol. 2001;  144 583-586
  • 23 Epinette W W, Parker C M, Jones E L, Greist M C. Mycophenolic acid for psoriasis: a review of pharmacology, long-term efficacy, and safty.  J Am Acad Dermatol. 1987;  17 962-971
  • 24 Grundmann-Kollmann M, Mooser G, Schraeder P, Zollner T, Kaskel P, Ochsendorf F, Boehncke W H, Kerscher M, Kaufmann R, Peter R U. Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil.  J Am Acad Dermatol. 2000;  42 835-837
  • 25 Xu X, Williams J W, Gong H. et al . Two activities of the immunosuppressive metabolite of leflunomide, A77 1726. Inhibition of pyrimidine nucleotide synthesis and protein tyrosine phosphorylation.  Biochem Pharmacol. 1996;  52 527-534
  • 26 Reich K, Hummel K M, Beckmann I, Mössner R, Neumann C. Treatment of severe psoriasis and psoriatic arthritis with leflunomide.  Br J Dermatol. 2002;  146 335-336
  • 27 Krueger J G, Walters I B, Miyazawa M, Gilleaudeau P, Hakimi J, Light S, Sherr A, Gottlieb A B. Successful in vivo blockade of CD25 (high-affinity interleukin 2 receptor) on T cells by administration of humanized anti-Tac antibody to patients with psoriasis.  J Am Acad Dermatol. 2000;  43 448-458
  • 28 Wohlrab J, Fischer M, Taube K M, Marsch W C. Treatment of recalcitrant psoriasis with daclizumab.  Br J Dermatol. 2001;  144 209-210
  • 29 Gottlieb A B, Bos J D. Recombinantly engineered human proteins: transforming the treatment of psoriasis.  Clin Immunol. 2002;  105 105-116
  • 30 Mrowietz U, Zhu K, Christophers E. Treatment of severe psoriasis with anti-CD25 monoclonal antibodies.  Arch Dermatol. 2000;  136 675-676
  • 31 Bagel J, Garland W T, Breneman D, Holick M, Littlejohn T W, Crosby D, Faust H, Fivenson D, Nichols J. Administration of DAB389IL-2 to patients with recalcitrant psoriasis: a double-blind, phase II multicenter trial.  J Am Acad Dermatol. 1998;  38 938-944
  • 32 Gottlieb S L, Gilleaudau P, Johnson R, Estes L, Woodworth T G, Gottlieb A B, Krueger J G. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenetic basis.  Nature Medicine. 1995;  1 442-447
  • 33 Gottlieb A B, Lebwohl M, Shirin S, Sherr A, Gilleaudeau P, Singer G, Solodkina G, Grossman R, Gisoldi E, Phillips S, Neisler H M, Krueger J G. Anti-CD4 monoclonal antibody treatment of moderate to severe psoriasis vulgaris: results of a pilot, multicenter, multiple-dose, placebo-controlled study.  J Am Acad Dermatol. 2000;  43 595-604
  • 34 Branco L, Barren P, Mao S Y, Pfarr D, Kaplan R, Postema C, Langermann S, Koenig S, Johnson S. Selective deletion of antigen-specific, activated T cells by a humanized MAB to CD2 (MEDI-507) is mediated by NK cells.  Transplantation. 1999;  68 1588-1596
  • 35 Bashir S J, Maibach H I. Alefacept (Biogen).  Curr Opin Investig Drugs. 2001;  2 631-634
  • 36 Krueger G G, Papp K A, Stough D B, Loven K H, Gulliver W P, Ellis C N. A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis.  J Am Acad Dermatol. 2002;  47 821-833
  • 37 Gottlieb A B, Krueger J G, Wittkowski K, Dedrick R, Walicke P A, Garovoy M. Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody.  Arch Dermatol. 2002;  138 591-600
  • 38 Cather J C, Cather J C, Menter A. Modulating T cell responses for the treatment of psoriasis: a focus on efalizumab.  Expert Opin Biol Ther. 2003;  3 361-370
  • 39 Schön M P, Krahn T, Schön M, Rodriguez M L, Antonicek H, Schultz J E, Ludwig R J, Zollner T M, Bischoff E, Bremm K D, Schramm M, Henninger K, Kaufmann R, Gollnick H P, Parker C M, Boehncke W H. Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation.  Nat Med. 2002;  8 366-372
  • 40 Ghoreschi K. et al . Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.  Nat Med. 2003;  9 40-46
  • 41 Asadullah K, Docke W D, Sabat R V, Volk H D, Sterry W. The treatment of psoriasis with IL-10: rationale and review of the first clinical trials.  Expert Opin Investig Drugs. 2000;  9 95-102
  • 42 Friedrich M, Docke W D, Klein A, Philipp S, Volk H D, Sterry W, Asadullah K. Immunomodulation by interleukin-10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in psoriasis.  J Invest Dermatol. 2002;  118 672-677
  • 43 Trepicchio W L, Ozawa M, Walters I B, Kikuchi T, Gilleaudeau P, Bliss J L, Schwertschlag U, Dorner A J, Krueger J G. Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions.  J Clin Invest. 1999;  104 1527-1537

Prof. Dr. Dr. C. C. Geilen

Klinik und Poliklinik für Dermatologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin

Fabeckstraße 60-62 · 14195 Berlin-Dahlem

Email: ccgeilen@zedat.fu-berlin.de

    >