Recent developments in the use of biologics in psoriasis and autoimmun
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《英国医生杂志》
1 Department of Dermatology, University of Kiel, 24105 Kiel, Germany
Correspondence to: U Mrowietz umrowietz@dermatology.uni-kiel.de
We searched Medline and obtained original articles through the library service. We also used relevant pages found through an internet search using Google and included data from the Annual European Congress of Rheumatology held in Berlin in June 2004.
Induction of antibodies against biologics
The development of antinuclear antibodies and autoimmune disorders has been observed after treatment with TNF- inhibitors (box 3, table 2).12 15 To our knowledge, no autoimmunity related phenomena after treatment with alefacept or efalizumab have been reported. Besides its important role as a proinflammatory cytokine, TNF- also causes serious immunosuppressive effects by regulating antigen-presenting cell functions and apoptosis of potentially autoreactive T cells.w27 Therefore, antagonising TNF- and its suppressive effects may lead to the development or unmasking of autoimmune diseases.21 22 It remains unclear whether the detection of anti-doublestranded DNA antibodies is predictive of an increased risk of developing lupus-like syndrome or systemic lupus erythematosus. Box 4 gives details of trials of autoimmunity during treatment with TNF- inhibitors.
Table 2 Autoimmunity associated with TNF- inhibitors
Box 3: Autoimmune diseases and autoantibodies that may occur during treatment with TNF- inhibitors
Lupus-like syndrome
Leukocytoclastic vasculitis
Systemic lupus erythematosus
Antinuclear antibodies
Anti-doublestranded DNA
Case reports of drug induced lupus after treatment with infliximab and etanercept have been published22 w28-w31 and a French national survey found 12 cases of systemic lupus erythematosus after anti-TNF- therapy (in about 7000 patients treated) for inflammatory arthritis.23 Despite the relatively high incidence of anti-doublestranded DNA antibodies, the frequency of clinical lupus related to anti-TNF- treatment is very low. No evidence exists that patients who develop new autoantibodies are at significantly increased risk of developing drug induced lupus, but the long term impact remains unclear.21 24 The risk of developing self limiting autoimmune syndromes seems in most cases to be small compared with the impressive clinical benefit the patients experience with these drugs. Nevertheless these findings underline the need for further monitoring of autoantibody production in patients treated with TNF- antagonists over longer periods. Physicians therefore need to look for signs and symptoms of autoimmune disorders when using TNF- antagonists.
Risk of lymphoma development
Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2004;51: 534-42.
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48: 35-45.
Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (safety trial of adalimumab in rheumatoid arthritis). J Rheumatol 2003;30: 2563-71.
Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 2003;139: 1627-32.
Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349: 2014-22.
Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN. 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: 821-33.
Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003;349: 2004-13.
Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340: 253-9.
Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM. Tumor necrosis factor antagonist therapy and lymphoma development: twentysix cases reported to the Food and Drug Administration. Arthritis Rheum 2002;46: 3151-8.
Antoni C, Braun J. Side effects of anti-TNF therapy: current knowledge. Clin Exp Rheumatol 2002;20: S152-7.
Weisman MH. What are the risks of biologic therapy in rheumatoid arthritis? An update on safety. J Rheumatol Suppl 2002;65: 33-8.
Vermeire S, Noman M, van Assche G, Baert F, van Steen K, Esters N, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn's disease: a prospective cohort study. Gastroenterology 2003;125: 32-9.
Charles PJ, Smeenk RJ, de Jong J, Feldmann M, Maini RN. Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 2000;43: 2383-90.
Bobbio-Pallavicini F, Alpini C, Caporali R, Avalle S, Bugatti S, Montecucco C. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. Arthritis Res Ther 2004;6: R264-72.
De Rycke L, Kruithof E, van Damme N, Hoffman IE, van den BN, van den BF, et al. Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. Arthritis Rheum 2003;48: 1015-23.
Van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004;63: 508-16.
Baert F, Noman M, Vermeire S, van Assche G, D'Haens G, Carbonez A, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348: 601-8.
Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology 2003;124: 917-24.
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359: 1541-9.
Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004;50: 1400-11.
Ferraro-Peyret C, Coury F, Tebib JG, Bienvenu J, Fabien N. Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study. Arthritis Res Ther 2004;6: R535-43.
Stratigos AJ, Antoniou C, Stamathioudaki S, Avgerinou G, Tsega A, Katsambas AD. Discoid lupus erythematosus-like eruption induced by infliximab. Clin Exp Dermatol 2004;29: 150-3.
De Bandt MJ, Sibilia J, Le Loet X, Prouzeau S, Fautrel B, Marcelli C, et al. Systemic lupus erythematosus induced by anti-TNF-alpha therapy: a French national survey. Ann Rheum Dis 2004;63(suppl 28): 213-4.
Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW, et al. Updated consensus statement on biological agents, specifically tumour necrosis factor alpha (TNFalpha) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases. Ann Rheum Dis 2004;63(suppl 2): ii2-12.(Silja Rott, resident1, Ulrich Mrowietz, )
Correspondence to: U Mrowietz umrowietz@dermatology.uni-kiel.de
We searched Medline and obtained original articles through the library service. We also used relevant pages found through an internet search using Google and included data from the Annual European Congress of Rheumatology held in Berlin in June 2004.
Induction of antibodies against biologics
The development of antinuclear antibodies and autoimmune disorders has been observed after treatment with TNF- inhibitors (box 3, table 2).12 15 To our knowledge, no autoimmunity related phenomena after treatment with alefacept or efalizumab have been reported. Besides its important role as a proinflammatory cytokine, TNF- also causes serious immunosuppressive effects by regulating antigen-presenting cell functions and apoptosis of potentially autoreactive T cells.w27 Therefore, antagonising TNF- and its suppressive effects may lead to the development or unmasking of autoimmune diseases.21 22 It remains unclear whether the detection of anti-doublestranded DNA antibodies is predictive of an increased risk of developing lupus-like syndrome or systemic lupus erythematosus. Box 4 gives details of trials of autoimmunity during treatment with TNF- inhibitors.
Table 2 Autoimmunity associated with TNF- inhibitors
Box 3: Autoimmune diseases and autoantibodies that may occur during treatment with TNF- inhibitors
Lupus-like syndrome
Leukocytoclastic vasculitis
Systemic lupus erythematosus
Antinuclear antibodies
Anti-doublestranded DNA
Case reports of drug induced lupus after treatment with infliximab and etanercept have been published22 w28-w31 and a French national survey found 12 cases of systemic lupus erythematosus after anti-TNF- therapy (in about 7000 patients treated) for inflammatory arthritis.23 Despite the relatively high incidence of anti-doublestranded DNA antibodies, the frequency of clinical lupus related to anti-TNF- treatment is very low. No evidence exists that patients who develop new autoantibodies are at significantly increased risk of developing drug induced lupus, but the long term impact remains unclear.21 24 The risk of developing self limiting autoimmune syndromes seems in most cases to be small compared with the impressive clinical benefit the patients experience with these drugs. Nevertheless these findings underline the need for further monitoring of autoantibody production in patients treated with TNF- antagonists over longer periods. Physicians therefore need to look for signs and symptoms of autoimmune disorders when using TNF- antagonists.
Risk of lymphoma development
Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2004;51: 534-42.
Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, et al. Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003;48: 35-45.
Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human anti tumor necrosis factor-alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (safety trial of adalimumab in rheumatoid arthritis). J Rheumatol 2003;30: 2563-71.
Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, et al. A randomized trial of etanercept as monotherapy for psoriasis. Arch Dermatol 2003;139: 1627-32.
Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med 2003;349: 2014-22.
Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN. 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: 821-33.
Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 2003;349: 2004-13.
Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 1999;340: 253-9.
Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM. Tumor necrosis factor antagonist therapy and lymphoma development: twentysix cases reported to the Food and Drug Administration. Arthritis Rheum 2002;46: 3151-8.
Antoni C, Braun J. Side effects of anti-TNF therapy: current knowledge. Clin Exp Rheumatol 2002;20: S152-7.
Weisman MH. What are the risks of biologic therapy in rheumatoid arthritis? An update on safety. J Rheumatol Suppl 2002;65: 33-8.
Vermeire S, Noman M, van Assche G, Baert F, van Steen K, Esters N, et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn's disease: a prospective cohort study. Gastroenterology 2003;125: 32-9.
Charles PJ, Smeenk RJ, de Jong J, Feldmann M, Maini RN. Assessment of antibodies to double-stranded DNA induced in rheumatoid arthritis patients following treatment with infliximab, a monoclonal antibody to tumor necrosis factor alpha: findings in open-label and randomized placebo-controlled trials. Arthritis Rheum 2000;43: 2383-90.
Bobbio-Pallavicini F, Alpini C, Caporali R, Avalle S, Bugatti S, Montecucco C. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment. Arthritis Res Ther 2004;6: R264-72.
De Rycke L, Kruithof E, van Damme N, Hoffman IE, van den BN, van den BF, et al. Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. Arthritis Rheum 2003;48: 1015-23.
Van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis 2004;63: 508-16.
Baert F, Noman M, Vermeire S, van Assche G, D'Haens G, Carbonez A, et al. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med 2003;348: 601-8.
Farrell RJ, Alsahli M, Jeen YT, Falchuk KR, Peppercorn MA, Michetti P. Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn's disease: a randomized controlled trial. Gastroenterology 2003;124: 917-24.
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet 2002;359: 1541-9.
Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004;50: 1400-11.
Ferraro-Peyret C, Coury F, Tebib JG, Bienvenu J, Fabien N. Infliximab therapy in rheumatoid arthritis and ankylosing spondylitis-induced specific antinuclear and antiphospholipid autoantibodies without autoimmune clinical manifestations: a two-year prospective study. Arthritis Res Ther 2004;6: R535-43.
Stratigos AJ, Antoniou C, Stamathioudaki S, Avgerinou G, Tsega A, Katsambas AD. Discoid lupus erythematosus-like eruption induced by infliximab. Clin Exp Dermatol 2004;29: 150-3.
De Bandt MJ, Sibilia J, Le Loet X, Prouzeau S, Fautrel B, Marcelli C, et al. Systemic lupus erythematosus induced by anti-TNF-alpha therapy: a French national survey. Ann Rheum Dis 2004;63(suppl 28): 213-4.
Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW, et al. Updated consensus statement on biological agents, specifically tumour necrosis factor alpha (TNFalpha) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases. Ann Rheum Dis 2004;63(suppl 2): ii2-12.(Silja Rott, resident1, Ulrich Mrowietz, )