FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 349:2014-2022 November 20, 2003 Number 21 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Kupper, T. S. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Inflammatory cytokines such as tumor necrosis factor (TNF) have been implicated in the pathogenesis of psoriasis. We evaluated the safety and efficacy of etanercept, a TNF antagonist, for the treatment of plaque psoriasis.

Methods In this 24-week, double-blind study, 672 patients underwent randomization and 652 either received placebo or received etanercept subcutaneously at a low dose (25 mg once weekly), a medium dose (25 mg twice weekly), or a high dose (50 mg twice weekly). After 12 weeks, patients in the placebo group began twice-weekly treatment with 25 mg of etanercept. The primary measure of clinical response was the psoriasis area-and-severity index.

Results At week 12, there was an improvement from base line of 75 percent or more in the psoriasis area-and-severity index in 4 percent of the patients in the placebo group, as compared with 14 percent of those in the low-dose–etanercept group, 34 percent in the medium-dose–etanercept group, and 49 percent in the high-dose–etanercept group (P<0.001 for all three comparisons with the placebo group). The clinical responses continued to improve with longer treatment. At week 24, there was at least a 75 percent improvement in the psoriasis area-and-severity index in 25 percent of the patients in the low-dose group, 44 percent of those in the medium-dose group, and 59 percent in the high-dose group. The responses as measured by improvements in the psoriasis area-and-severity index were paralleled by improvements in global assessments by physicians and the patients and in quality-of-life measures. Etanercept was generally well tolerated.

Conclusions The treatment of psoriasis with etanercept led to a significant reduction in the severity of disease over a period of 24 weeks.

Source Information

From the Saint Louis University School of Medicine, St. Louis (C.L.L.); Radiant Research, Scottsdale, Ariz. (J.L.P.); Oregon Medical Research Center, Portland (R.T.M.); Minor and James Medical Center, Seattle (B.S.G.); Amgen, Thousand Oaks, Calif. (R.Z., A.W.); and the University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, New Brunswick (A.B.G.).

Address reprint requests to Dr. Gottlieb at the University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Clinical Research Center, 1 Robert Wood Johnson Medical School, New Brunswick, NJ 08903, or at gottliab{at}umdnj.edu.

Full Text of this Article

This article has been cited by other articles:

• Goto, M., Chow, J., Muramoto, K., Chiba, K.-i., Yamamoto, S., Fujita, M., Obaishi, H., Tai, K., Mizui, Y., Tanaka, I., Young, D., Yang, H., Wang, Y. J., Shirota, H., Gusovsky, F. (2009). E6201 [(3S,4R,5Z,8S,9S,11E)-14-(Ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase (MEK)-1 and MEK Kinase-1: In Vitro Characterization of Its Anti-Inflammatory and Antihyperproliferative Activities. J. Pharmacol. Exp. Ther. 331: 485-495 [Abstract] [Full Text]  
• Wang, H., Syrovets, T., Kess, D., Buchele, B., Hainzl, H., Lunov, O., Weiss, J. M., Scharffetter-Kochanek, K., Simmet, T. (2009). Targeting NF-{kappa}B with a Natural Triterpenoid Alleviates Skin Inflammation in a Mouse Model of Psoriasis. J. Immunol. 183: 4755-4763 [Abstract] [Full Text]  
• Ritchlin, C T, Kavanaugh, A, Gladman, D D, Mease, P J, Helliwell, P, Boehncke, W-H, de Vlam, K, Fiorentino, D, FitzGerald, O, Gottlieb, A B, McHugh, N J, Nash, P, Qureshi, A A, Soriano, E R, Taylor, W J, for the Group for Research and Assessment of Psori, (2009). Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 68: 1387-1394 [Abstract] [Full Text]  
• Chang, B. Y., Zhao, F., He, X., Ren, H., Braselmann, S., Taylor, V., Wicks, J., Payan, D. G., Grossbard, E. B., Pine, P. R., Bullard, D. C. (2009). JAK3 Inhibition Significantly Attenuates Psoriasiform Skin Inflammation in CD18 Mutant PL/J Mice. J. Immunol. 183: 2183-2192 [Abstract] [Full Text]  
• Koek, M. B G, Buskens, E., van Weelden, H., Steegmans, P. H A, Bruijnzeel-Koomen, C. A F M, Sigurdsson, V. (2009). Home versus outpatient ultraviolet B phototherapy for mild to severe psoriasis: pragmatic multicentre randomised controlled non-inferiority trial (PLUTO study). BMJ 338: b1542-b1542 [Abstract] [Full Text]  
• Nair, R. P., Ding, J., Duffin, K. C., Helms, C., Voorhees, J. J., Krueger, G. G., Bowcock, A. M., Abecasis, G. R., Elder, J. T. (2009). Psoriasis Bench to Bedside: Genetics Meets Immunology. Arch Dermatol 145: 462-464 [Full Text]  
• Winfield, R. D., Delano, M. J., Pande, K., Scumpia, P. O., LaFace, D., Moldawer, L. L. (2008). Myeloid-Derived Suppressor Cells in Cancer Cachexia Syndrome: A New Explanation for an Old Problem. JPEN J Parenter Enteral Nutr 32: 651-655 [Abstract] [Full Text]  
• Raghu, G., Brown, K. K., Costabel, U., Cottin, V., du Bois, R. M., Lasky, J. A., Thomeer, M., Utz, J. P., Khandker, R. K., McDermott, L., Fatenejad, S. (2008). Treatment of Idiopathic Pulmonary Fibrosis with Etanercept: An Exploratory, Placebo-controlled Trial. Am. J. Respir. Crit. Care Med. 178: 948-955 [Abstract] [Full Text]  
• Paller, A. S., Siegfried, E. C., Langley, R. G., Gottlieb, A. B., Pariser, D., Landells, I., Hebert, A. A., Eichenfield, L. F., Patel, V., Creamer, K., Jahreis, A., the Etanercept Pediatric Psoriasis Study Group, (2008). Etanercept Treatment for Children and Adolescents with Plaque Psoriasis. NEJM 358: 241-251 [Abstract] [Full Text]  
• MacDonald, A, Burden, A D (2007). Psoriasis: advances in pathophysiology and management. Postgrad. Med. J. 83: 690-697 [Abstract] [Full Text]  
• Gelfand, J. M. (2007). Long-term Treatment for Severe Psoriasis: We're Halfway There, With a Long Way to Go. Arch Dermatol 143: 1191-1193 [Full Text]  
• Stern, R. S. (2007). Psoralen and Ultraviolet A Light Therapy for Psoriasis. NEJM 357: 682-690 [Full Text]  
• Tyring, S., Gordon, K. B., Poulin, Y., Langley, R. G., Gottlieb, A. B., Dunn, M., Jahreis, A. (2007). Long-term Safety and Efficacy of 50 mg of Etanercept Twice Weekly in Patients With Psoriasis. Arch Dermatol 143: 719-726 [Abstract] [Full Text]  
• Kuek, A., Hazleman, B. L, Ostor, A. J K (2007). Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad. Med. J. 83: 251-260 [Abstract] [Full Text]  
• Krueger, G. G., Langley, R. G., Leonardi, C., Yeilding, N., Guzzo, C., Wang, Y., Dooley, L. T., Lebwohl, M., the CNTO 1275 Psoriasis Study Group, (2007). A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis. NEJM 356: 580-592 [Abstract] [Full Text]  
• Hutmacher, M. M., Nestorov, I., Ludden, T., Zitnik, R., Banfield, C. (2007). Modeling the Exposure-Response Relationship of Etanercept in the Treatment of Patients With Chronic Moderate to Severe Plaque Psoriasis. J Clin Pharmacol 47: 238-248 [Abstract] [Full Text]  
• van der Heijde, D, Da Silva, J C, Dougados, M, Geher, P, van der Horst-Bruinsma, I, Juanola, X, Olivieri, I, Raeman, F, Settas, L, Sieper, J, Szechinski, J, Walker, D, Boussuge, M-P, Wajdula, J S, Paolozzi, L, Fatenejad, S, for the Etanercept Study 314 Investigators, (2006). Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 65: 1572-1577 [Abstract] [Full Text]  
• Chan, J. R., Blumenschein, W., Murphy, E., Diveu, C., Wiekowski, M., Abbondanzo, S., Lucian, L., Geissler, R., Brodie, S., Kimball, A. B., Gorman, D. M., Smith, K., de Waal Malefyt, R., Kastelein, R. A., McClanahan, T. K., Bowman, E. P. (2006). IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. JEM 203: 2577-2587 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Emery, P, Keystone, E C, Schiff, M H, van Riel, P L C M, Weinblatt, M E, Weisman, M H (2006). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 65: iii2-iii15 [Full Text]  
• Erin, E. M., Leaker, B. R., Nicholson, G. C., Tan, A. J., Green, L. M., Neighbour, H., Zacharasiewicz, A. S., Turner, J., Barnathan, E. S., Kon, O. M., Barnes, P. J., Hansel, T. T. (2006). The Effects of a Monoclonal Antibody Directed against Tumor Necrosis Factor-{alpha} in Asthma. Am. J. Respir. Crit. Care Med. 174: 753-762 [Abstract] [Full Text]  
• Massara, A., Cavazzini, P. L., Trotta, F. (2006). In SAPHO syndrome anti-TNF-{alpha} therapy may induce persistent amelioration of osteoarticular complaints, but may exacerbate cutaneous manifestations. Rheumatology (Oxford) 45: 730-733 [Abstract] [Full Text]  
• Shupack, J., Siu, K. (2006). Resolving granuloma annulare with etanercept.. Arch Dermatol 142: 394-395 [Full Text]  
• Gilhar, A., Yaniv, R., Assy, B., Serafimovich, S., Ullmann, Y., Kalish, R. S. (2006). Fas Pulls the Trigger on Psoriasis. Am. J. Pathol. 168: 170-175 [Abstract] [Full Text]  
• Lowes, M. A., Chamian, F., Abello, M. V., Fuentes-Duculan, J., Lin, S.-L., Nussbaum, R., Novitskaya, I., Carbonaro, H., Cardinale, I., Kikuchi, T., Gilleaudeau, P., Sullivan-Whalen, M., Wittkowski, K. M., Papp, K., Garovoy, M., Dummer, W., Steinman, R. M., Krueger, J. G. (2005). Increase in TNF-{alpha} and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc. Natl. Acad. Sci. USA 102: 19057-19062 [Abstract] [Full Text]  
• Davis, J C, van der Heijde, D M, Braun, J, Dougados, M, Cush, J, Clegg, D, Inman, R D, Kivitz, A, Zhou, L, Solinger, A, Tsuji, W (2005). Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks. Ann Rheum Dis 64: 1557-1562 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Bijlsma, J W J, Dougados, M, Emery, P, Keystone, E C, Klareskog, L, Mease, P J (2005). Updated consensus statement on biological agents, specifically tumour necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2005. Ann Rheum Dis 64: iv2-iv14 [Full Text]  
• Gottlieb, A. B., Chamian, F., Masud, S., Cardinale, I., Abello, M. V., Lowes, M. A., Chen, F., Magliocco, M., Krueger, J. G. (2005). TNF Inhibition Rapidly Down-Regulates Multiple Proinflammatory Pathways in Psoriasis Plaques. J. Immunol. 175: 2721-2729 [Abstract] [Full Text]  
• Nestle, F. O., Conrad, C., Tun-Kyi, A., Homey, B., Gombert, M., Boyman, O., Burg, G., Liu, Y.-J., Gilliet, M. (2005). Plasmacytoid predendritic cells initiate psoriasis through interferon-{alpha} production. JEM 202: 135-143 [Abstract] [Full Text]  
• Lin, M.-H., Hsu, C.-K., Lee, J. Y.-Y. (2005). Successful Treatment of Recalcitrant Pemphigus Vulgaris and Pemphigus Vegetans With Etanercept and Carbon Dioxide Laser. Arch Dermatol 141: 680-682 [Full Text]  
• Schön, M. P., Boehncke, W.-H. (2005). Psoriasis. NEJM 352: 1899-1912 [Full Text]  
• Rott, S., Mrowietz, U. (2005). Recent developments in the use of biologics in psoriasis and autoimmune disorders. The role of autoantibodies. BMJ 330: 716-720 [Full Text]  
• Kyle, S., Chandler, D., Griffiths, C. E. M., Helliwell, P., Lewis, J., McInnes, I., Oliver, S., Symmons, D., McHugh, N., on behalf of the British Society for Rheumatology, (2005). Guideline for anti-TNF-{alpha} therapy in psoriatic arthritis. Rheumatology (Oxford) 44: 390-397 [Full Text]  
• Veale, D J, Ritchlin, C, FitzGerald, O (2005). Immunopathology of psoriasis and psoriatic arthritis. Ann Rheum Dis 64: ii26-ii29 [Abstract] [Full Text]  
• Krueger, J G, Bowcock, A (2005). Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 64: ii30-ii36 [Abstract] [Full Text]  
• Feldman, S R, Krueger, G G (2005). Psoriasis assessment tools in clinical trials. Ann Rheum Dis 64: ii65-ii68 [Abstract] [Full Text]  
• Winterfield, L S, Menter, A, Gordon, K, Gottlieb, A (2005). Psoriasis treatment: current and emerging directed therapies. Ann Rheum Dis 64: ii87-ii90 [Abstract] [Full Text]  
• The Wegener's Granulomatosis Etanercept Trial (WGE, (2005). Etanercept plus Standard Therapy for Wegener's Granulomatosis. NEJM 352: 351-361 [Abstract] [Full Text]  
• Berman, J., Girardi, G., Salmon, J. E. (2005). TNF-{alpha} Is a Critical Effector and a Target for Therapy in Antiphospholipid Antibody-Induced Pregnancy Loss. J. Immunol. 174: 485-490 [Abstract] [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Bijlsma, J W J, Dougados, M, Emery, P, Keystone, E C, Klareskog, L, Mease, P J (2004). Updated consensus statement on biological agents, specifically tumour necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases, 2004. Ann Rheum Dis 63: ii2-ii12 [Full Text]  
• Zhang, X., Kohli, M., Zhou, Q., Graves, D. T., Amar, S. (2004). Short- and Long-Term Effects of IL-1 and TNF Antagonists on Periodontal Wound Healing. J. Immunol. 173: 3514-3523 [Abstract] [Full Text]  
• Braun, J., Sieper, J. (2004). Biological therapies in the spondyloarthritides--the current state. Rheumatology (Oxford) 43: 1072-1084 [Abstract] [Full Text]  
• Dinarello, C. A. (2004). Review: Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. Innate Immunity 10: 201-222 [Abstract]  
• Mease, P (2004). TNF{alpha} therapy in psoriatic arthritis and psoriasis. Ann Rheum Dis 63: 755-758 [Full Text]  
• Stern, R. S. (2003). A Promising Step Forward in Psoriasis Therapy. JAMA 290: 3133-3135 [Full Text]  
• (2003). New Biologic Agents for Severe Psoriasis. JWatch General 2003: 2-2 [Full Text]  
• (2003). The Biologic Age Is Upon Us -- In Full Swing!. Journal Watch Dermatology 2003: 1-1 [Full Text]