Biologic therapy for psoriasis: an overview of infliximab, etanercept, adalimumab, efalizumab, and alefacept

  • Jeffrey M. Weinberg
Part of the Milestones in Drug Therapy book series (MDT)


The implication of an immunologic phenomena in the pathogenesis of psoriasis has led to research for new treatment options over the past few years [1]. The result has been the birth of biologic therapies, those drugs targeting the activity of T lymphocytes and cytokines responsible for the inflammatory nature of this disease. Singri et al. [2] defined four strategies that clarify the mechanism of action for the various biologic agents: (1) reduction of pathogenic T cells, (2) inhibition of T cell activation, (3) immune deviation (‘deviation’ of a TH1 immune response toward a greater TH2-type response through the involvement of these TH2-type cytokines), and (4) blocking the activity of inflammatory cytokines [2]. We have previously reviewed the utility of biologic agents for psoriasis [3]. In this article, we present an update on the progress of the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab (all strategy 4) as well as the T cell-targeted therapies efalizumab (strategy 2) and alefacept (strategy 1) (Tab. 1). Clinical data for these agents, including the most recent Phase II and/or III study results will be discussed, as well as the most recent safety data (Tab. 2).


Psoriatic Arthritis Standardize Incidence Ratio Plaque Psoriasis Dermatology Life Quality Index Tumor Necrosis Factor Antagonist 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Tutrone WD, Kagen MH, Barbagallo J, Weinberg JM (2001) Biologic therapy for psoriasis: a brief history, II. Cutis 68: 367–372PubMedGoogle Scholar
  2. 2.
    Singri P, West DP, Gordon KB (2002) Biologic therapy for psoriasis: the new therapeutic frontier. Arch Dermatol 138: 657–663PubMedCrossRefGoogle Scholar
  3. 3.
    Weinberg JM (2003) An overview of infliximab, etanercept, efalizumab, and alefacept as biologic therapy for psoriasis. Clin Ther 25: 2487–2505PubMedCrossRefGoogle Scholar
  4. 4.
    Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, Bala M, Marano CW, Menter A (2004) Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 51: 534–542PubMedCrossRefGoogle Scholar
  5. 5.
    Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE; EXPRESS study investigators (2005) Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 366: 1367–1374PubMedCrossRefGoogle Scholar
  6. 6.
    Leonardi C, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, Gottlieb AB; Etanercept Psoriasis Study Group (2003) Etanercept as monotherapy in patients with psoriasis. N Engl J Med 349: 2014–2022PubMedCrossRefGoogle Scholar
  7. 7.
    Papp KA, Tyring S, Lahfa M, Prinz J, Griffiths CE, Nakanishi AM, Zitnik R, van de Kerkhof PC, Melvin L; Etanercept Psoriasis Study Group (2005) A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol 152: 1304–1312PubMedCrossRefGoogle Scholar
  8. 8.
    Magliocco MA, Gottlieb AB (2004) Etanercept therapy for patients with psoriatic arthritis and concurrent hepatitis C virus infection: report of 3 cases. J Am Acad Dermatol 51: 580–584PubMedCrossRefGoogle Scholar
  9. 9.
    (2003) Adalimumab (HUMIRA) for rheumatoid arthritis. Med Lett Drugs Ther 45: 25–27Google Scholar
  10. 10.
    Gordon KB, Leonardi C, Menter MA, Langley R, Chen DM (2004) Adalimumab efficacy and safety in patients with moderate to severe chronic plaque psoriasis: preliminary findings from a 12-week dose-ranging trial. Poster presented at: American Academy of Dermatology, 62nd Annual Meeting, Washington, DC, 6–11 February 2004, Poster 2Google Scholar
  11. 11.
    Langley R, Leonardi C, Toth D, Hoofman R (2005) Long-term safety and efficacy of adalimumab in the treatment of moderate to severe chronic plaque psoriasis. Poster presented at: 63rd Annual Meeting of the American Academy of Dermatology; 18–22 February 2005; New Orleans, LA, Poster 8Google Scholar
  12. 12.
    Lebwohl M (2002) New developments in the treatment of psoriasis. Arch Dermatol 138: 686–688PubMedCrossRefGoogle Scholar
  13. 13.
    Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345: 1098–1104 Bresnihan B, Cunnane G (2003) Infection complications associated with the use of biologic agents. Rheum Dis Clin North Am 29: 185–202PubMedCrossRefGoogle Scholar
  14. 14.
    Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R, Vinh DC (2003) Antitumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 3: 148–155PubMedCrossRefGoogle Scholar
  15. 15.
    Hamilton CD (2004) Infectious complications of treatment with biologic agents. Curr Opin Rheumatol 16: 393–398PubMedCrossRefGoogle Scholar
  16. 16.
    Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM (2002) Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 46: 3151–3158PubMedCrossRefGoogle Scholar
  17. 17.
    Wolfe F, Michaud K (2004) Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18’572 patients. Arthritis Rheum 50: 1740–1751PubMedCrossRefGoogle Scholar
  18. 18.
    Adams AE, Zwicker J, Curiel C, Kadin ME, Falchuk KR, Drews R, Kupper TS (2004) Aggressive cutaneous T-cell lymphomas after TNF alpha blockade. J Am Acad Dermatol 51: 660–662PubMedCrossRefGoogle Scholar
  19. 19.
    Wed MD (2005) Available at: Accessed 11 September 2005
  20. 20.
    FDA Advisory Committee (2005) Arthritis Committee. Will discuss risk of lymphoma with TNF inhibitors at March 4 meeting. Available at:±Drugs/030403_TNFsafety/030403_TNFsafetyP.htm. Accessed 11 September 2005
  21. 21.
    Mohan N, Edwards ET, Cupps TR, Oliverio PJ, Sandberg G, Crayton H, Richert JR, Siegel JN (2001) Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 44: 2862–2869PubMedCrossRefGoogle Scholar
  22. 22.
    Kwon HJ, Cote TR, Cuffe MS, Kramer JM, Braun MM (2003) Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med 138: 807–811PubMedGoogle Scholar
  23. 23.
    Debandt M, Vittecoq O, Descamps V, Le Loet X, Meyer O (2003) Anti-TNF-alpha-induced systemic lupus syndrome. Clin Rheumatol 22: 56–61PubMedCrossRefGoogle Scholar
  24. 24.
    Watts RA (2000) Musculoskeletal and systemic reactions to biological therapeutic agents. Curr Opin Rheumatol 12: 49–52PubMedCrossRefGoogle Scholar
  25. 25.
    Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M et al. (1999) Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354: 1932–1939PubMedCrossRefGoogle Scholar
  26. 26.
    Rutgeerts P, D’Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL et al. (1999) Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 117: 761–769PubMedCrossRefGoogle Scholar
  27. 27.
    Shakoor N, Michalska M, Harris CA, Block JA (2002) Drug-induced systemic lupus erythematosus associated with etanercept therapy [letter]. Lancet 359: 579–580PubMedCrossRefGoogle Scholar
  28. 28.
    Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, Walicke P, Dummer W, Wang X, Garovoy MR et al. (2003) A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 349: 2004–2013PubMedCrossRefGoogle Scholar
  29. 29.
    Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, Bresnahan BW, Menter A; Efalizumab Study Group (2003) Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA 290: 3073–3080PubMedCrossRefGoogle Scholar
  30. 30.
    Menter A, Kardatzke D, Rundle AC, Kwon P, Garovoy MR, Leonardi CL (2004) Incidence and prevention of rebound upon efalizumab discontinuation. Poster presented at: 10th International Psoriasis Symposium, Toronto, Canada, 10–13 June 2004Google Scholar
  31. 31.
    Toth DP, Papp KA (2004) Managing recurrence of psoriasis following abrupt withdrawal form efalizumab therapy. Poster presented at: 10th International Psoriasis Symposium, Toronto, Canada, 10–13 June 2004Google Scholar
  32. 32.
    Cather JC, Menter A (2005) Efalizumab: continuous therapy for chronic psoriasis. Expert Opin Biol Ther 5: 393–403PubMedCrossRefGoogle Scholar
  33. 33.
    Lebwohl M (2002) New developments in the treatment of psoriasis. Arch Dermatol 138: 686–688PubMedCrossRefGoogle Scholar
  34. 34.
    RAPTIVA® (efalizumab) package insert. South San Francisco, Calif: Genentech, Inc; 2005Google Scholar
  35. 35.
    Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE, Alefacept Clinical Study Group (2003) An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol 139: 719–727PubMedCrossRefGoogle Scholar
  36. 36.
    Krueger GG, Ellis CN (2003) Alefacept therapy produces remission for patients with chronic plaque psoriasis. Br J Dermatol 148: 784–788PubMedCrossRefGoogle Scholar
  37. 37.
    Ellis CN, Krueger GG (2001) Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med 345: 248–255PubMedCrossRefGoogle Scholar
  38. 38.
    Gribetz CH, Blum R, Brady C, Cohen S, Lebwohl M (2004) Safety and efficacy of an extended course (16 weeks) of alefacept in the treatment of chronic plaque psoriasis. Poster presented at: Summer Academy 2004 of the American Academy of Dermatology; 28 July–1 August 2004; New York, Poster 74Google Scholar
  39. 39.
    AMEVIVE® (alefacept package insert). Cambridge, Mass: Biogen, Inc; 2005Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2008

Authors and Affiliations

  • Jeffrey M. Weinberg
    • 1
  1. 1.Department of DermatologySt. Luke’s-Roosevelt Hospital Center and Beth Israel Medical CenterNew YorkUSA

Personalised recommendations