TNF Pathophysiology

Molecular and Cellular Mechanisms

Editor(s): Kollias G. (Vari) 
Sfikakis P.P. (Athens) 
Table of Contents
Vol. 11, No. , 2010
Section title: Paper
Kollias G, Sfikakis PP (eds): TNF Pathophysiology. Molecular and Cellular Mechanisms. Curr Dir Autoimmun. Basel, Karger, 2010, vol 11, pp 180–210

The First Decade of Biologic TNF Antagonists in Clinical Practice: Lessons Learned, Unresolved Issues and Future Directions

Sfikakis P.P.
First Department of Propedeutic and Internal Medicine, Laikon Hospital, Athens University Medical School, Athens, Greece

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2–3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Sfikakis PP, Kollias G: Tumor necrosis factor biology in experimental and clinical arthritis. Curr Opin Rheumatol 2003;5:380-386
  2. Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, Braun J, Reed E, Gjertson D, Singh RR: TNFα blockade in human diseases: an overview of efficacy and safety. Clin Immunol 2008;126:13-30
  3. Tracey D, Klareskog L, Sasso EH, Selfeld JG, Tak PP: Tumor necrosis factor antagonist mechanisms of action. Pharmacol Ther 2008;117:244-279
  4. Wong M, Ziring D, Korin Y, Desai S, Kim S, Lin J, Gjertson D, Braun J, Reed E, Singh RR: TNFa blockade in human diseases: mechanisms and future directions. Clin Immunol 2008;126:121-136
  5. Fossati G, Nesbitt AM: In vitro complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity by the anti-TNF agents adalimumab, etanercept, infliximab, and certolizumab pegol (CDP870). Am J Gastroenterol 2005;100:S287
  6. Lugering A, Schmidt M, Lugering N, Pauels HG, Domschke W, Kucharzik T: Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 2001;121:1145-1157
  7. Mitoma H, Horiuchi T, Tsukamoto H: Binding activities of infliximab and etanercept to transmembrane tumor necrosis factor-alpha. Gastroenterology 2004;126:934-935author reply 935-936
  8. Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, Otsuka J, Okamura S, Fujita S, Harada M: Infliximab induces potent antiinflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology 2005;128:376-392
  9. Shen C, Van Assche G, Rutgeerts P, Ceuppens JL: Caspase activation and apoptosis induction by adalimumab: demonstration in vitro and in vivo in a chimeric mouse model. Inflamm Bowel Dis 2006;12:22-28
  10. Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C: Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002;301:418-426
  11. Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, vanDeventer SJ: Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 2003;124:1774-1785
  12. Arora T, Padaki R, Liu L, Hamburger AE, Ellison AR, Stevens SR, Louie JS, Kohno T: Differences in binding and effector functions between classes of TNF antagonists. Cytokine 2009;45:124-131
  13. Gramlick A, Fossati G, Nesbitt AM: Neutralization of soluble and membrane tumor necrosis factor (TNF) by infliximab, adalimumab, or certolizumab pegol using p55 or p75 TNF-receptor-specific bioassays. Gastroenterology 2006;130:697
  14. Mitoma H, Horiuchi T, Tsukamoto H, Tamimoto Y, Kimoto Y, Uchino A, To K, Harashima S, Hatta N, Harada M: Mechanisms for cytotoxic effects of antitumor necrosis factor agents on transmembrane tumor necrosis factor alpha-expressing cells: comparison among infliximab, etanercept, and adalimumab. Arthritis Rheum 2008;58:1248-1257
  15. Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK, Salfeld J, Sasso EH: Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol 2009;131:308-316
  16. Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, Hansen RA, Morgan LC, Lohr KN: Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med 2008;148:124-134
  17. Genovese MC, Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, Wasko MC, Moreland LW, Weaver AL, Markenson J, Cannon GW, Spencer-Green G, Finck BK: Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443-1450
  18. Weinblatt M, Kremer J, Bankhurst A, Bulpitt K, Fleischmann R, Fox R, Jackson C, Lange M, Burge D: 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;340:253-259
  19. Moreland L, Schiff M, Baumgartner S, Tindall E, Fleischmann R, Bulpitt K, Weaver A, Keystone E, Furst D, Mease P, Ruderman E, Horwitz D, Arkfeld D, Garrison L, Burge D, Blosch C, Lange M, McDonnell N, Weinblatt M: Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 1999;130:478-486
  20. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN: Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group: N Engl J Med 2000;343:1594-1602
  21. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH, Birbara CA, Teoh LA, Fischkoff SA, Chartash EK: Adalimumab, a fully human antitumor 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
  22. Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, Fischkoff SA, Chartash EK: 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;50:1400-1411
  23. Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675-681
  24. van de Putte LB, Atkins C, Malaise M, Sany J, Russell AS, van Riel PL, Settas L, Bijlsma JW, Todesco S, Dougados M, Nash P, Emery P, Walter N, Kaul M, Fischkoff S, Kupper H: 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;63:508-516
  25. St Clair EW, van der Heijde DM, Smolen JS, Maini RN, Bathon JM, Emery P, Keystone E, Schiff M, Kalden JR, Wang B, Dewoody K, Weiss R, Baker D: Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004;50:3432-3443
  26. Smolen JS, Van Der Heijde DM, St Clair EW, Emery P, Bathon JM, Keystone E, Maini RN, Kalden JR, Schiff M, Baker D, Han C, Han J, Bala M: Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum 2006;54:702-710
  27. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT: The PREMIER study: a multi-center, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006;54:26-37
  28. Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, Hsia EC, Han J, Wagner C, Xu Z, Visvanathan S, Rahman MU: Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum 2008;58:964-975
  29. Keystone E, Heijde D, Mason D Jr, Landewé R, Vollenhoven RV, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K: Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 2008;58:3319-3329
  30. Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, Pazdur J, Bae SC, Palmer W, Zrubek J, Wiekowski M, Visvanathan S, Wu Z, Rahman MU: Golimumab, a human antibody to tumour necrosis factor alpha given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis 2009;68:789-796
  31. Smolen J, Landewé RB, Mease P, Brzezicki J, Mason D, Luijtens K, van Vollenhoven RF, Kavanaugh A, Schiff M, Burmester GR, Strand V, Vencovsky J, van der Heijde D: Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis 2009;68:797-804
  32. Fleischmann R, Vencovsky J, van Vollenhoven RF, Borenstein D, Box J, Coteur G, Goel N, Brezinschek HP, Innes A, Strand V: Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis 2009;68:805-811
  33. van der Bijl AE, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Ten Wolde S, Han KH, van Krugten MV, Allaart CF, Breedveld FC, Dijkmans BA: Infliximab and methotrexate as induction therapy in patients with early rheumatoid arthritis. Arthritis Rheum 2007;56:2629-2634
  34. van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Güler-Yüksel M, Zwinderman AH, Kerstens PJ, van der Lubbe PA, de Beus WM, Grillet BA, Ronday HK, Huizinga TW, Breedveld FC, Dijkmans BA, Allaart CF: Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 2009;68:914-921
  35. Zink A, Strangfeld A, Schneider M, Herzer P, Hierse F, Stoyanova-Scholz M, Wassenberg S, Kapelle A, Listing J: Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials. Arthritis Rheum 2006;54:3399-3407
  36. Kievit W, Fransen J, Oerlemans AJ, Kuper HH, van der Laar MA, de Rooij DJ, De Gendt CM, Ronday KH, Jansen TL, van Oijen PC, Brus HL, Adang EM, vanRiel PL: The efficacy of anti-TNF in rheumatoid arthritis, a comparison between randomised controlled trials and clinical practice. Ann Rheum Dis 2007;66:1473-1478
  37. Greenberg JD, Kishimoto M, Strand V, Cohen SB, Olenginski TP, Harrington T, Kafka SP, Reed G, Kremer JM: Consortium of Rheumatology Researchers of North America Investigators. Tumor necrosis factor antagonist responsiveness in a United States rheumatoid arthritis cohort. Am J Med 2008;121:532-538
  38. Pavelka K, Gatterová J, Tegzová D, Jarosová K, Tomasová Studýnková J, Svobodník A, Svihálek J, Dusek L, Vencovský J: Radiographic progression of rheumatoid arthritis in patients from the Czech National Registry receiving infliximab treatment. Clin Exp Rheumatol 2007;25:540-545
  39. Jacobsson LT, Turesson C, Gülfe A, Kapetanovic MC, Petersson IF, Saxne T, Geborek P: Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol 2005;32:1213-1218
  40. Barnabe C, Hanley DA: Effect of tumor necrosis factor alpha inhibition on bone density and turnover markers in patients with rheumatoid arthritis and spondyloarthropathy. Semin Arhritis Rheum 2008;Epub ahead of print
  41. Finckh A, Simard JF, Gabay C, Guerne PA: SCQM physicians: evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis. Ann Rheum Dis 2006;65:746-752
  42. Pavelka K, Jarosova K, Suchy D, Senolt L, Chroust K, Dusek L, Vencovsky J: Increasing the infliximab dose in rheumatoid arthritis patients: a randomized, double blind study failed to confirm its efficacy. Ann Rheum Dis 2009;68:1285-1289
  43. van Vollenhoven R, Harju A, Brannemark S, Klareskog L: Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense. Ann Rheum Dis 2003;62:1195-1198
  44. Wick MC, Ernestam S, Lindblad S, Bratt J, Klareskog L, vanVollenhoven RF: Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital. Scand J Rheumatol 2005;34:353-358
  45. Smolen JS, Kay J, Doyle MK, Landewé R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU: for the GO-AFTER study investigators: Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009;374:210-221
  46. Lovell DJ, Giannini EH, Reiff A, Cawkwell GD, Silverman ED, Nocton JJ, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore J, Finck BK: Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group: N Engl J Med 2000;342:763-769
  47. Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Lange M, Finck BK, Burge DJ: Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multi-center, open-label, extended-treatment trial. Arthritis Rheum 2003;48:218-226
  48. Ruperto N, Lovell DJ, Cuttica R, et al: Paediatric Rheumatology International Trials Organisation, Pediatric Rheumatology Collaborative Study Group: A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2007;56:3096-3106
  49. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarosova K, Nemcova D, Mouy R, Sandborg C, Bohnsack J, Elewaut D, Foeldvari I, Gerloni V, Rovensky J, Minden K, Vehe RK, Weiner LW, Horneff G, Huppertz HI, Olson NY, Medich JR, Carcereri-De-Prati R, McIlraith MJ, Giannini EH, Martini A: Pediatric Rheumatology Collaborative Study Group, Pediatric Rheumatology International Trials Organisation: Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 2008;359:810-820
  50. Horneff G, Ebert A, Fitter S, Minden K, Foeldvari I, Kümmerle-Deschner J, Thon A, Girschick HJ, Weller F, Huppertz HI: Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis. Rheumatology (Oxford) 2009;48:916-919
  51. Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, Sibilia J, Kone-Paut I, Gandon-Laloum S, LeBideau M, Bader-Meunier B, Mouy R, Debre M, Landais P, Prieur AM: Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 2003;48:1093-1101
  52. Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, Henrickson M, Watcher S, Reiff A: Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 2005;32:935-942
  53. Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschick HJ, Hospach T, Huppertz HI, Keitzer R, Kuster RM, Michels H, Moebius D, Rogalski B, Thon A: The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004;63:1638-1644
  54. Cinar M, Dinc A, Simsek I, Erdem H, Koc B, Pay S, Kilic S: Evaluation of the short-term efficacy of NSAIDs on patients with active ankylosing spondylitis in daily practice: a 3-month, longitudinal, observational study. Rheumatol Int 2009;Epub ahead of print
  55. Gorman JD, Sack KE, DavisJC Jr: Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002;346:1349-1356
  56. Brandt J, Khariouzov A, Listing J, Haibel H, Sorensen H, Grassnickel L, Rudwaleit M, Sieper J, Braun J: Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis. Arthritis Rheum 2003;48:1667-1675
  57. Davis JC Jr, van der HD, Braun J, Dougados M, Cush J, Clegg DO, Kivitz A, Fleischmann R, Inman R, Tsuji W: Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum 2003;48:3230-3236
  58. Calin A, Dijkmans BA, Emery P, Hakala M, Kalden J, Leirisalo-Repo M, Mola EM, Salvarani C, Sanmarti R, Sany J, Sibilia J, Sieper J, van der LS, Veys E, Appel AM, Fatenejad S: Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis 2004;63:1594-1600
  59. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, Gromnica-Ihle E, Kellner H, Krause A, Schneider M, Sorensen H, Zeidler H, Thriene W, Sieper J: Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187-1193
  60. Braun J, Brandt J, Listing J, Zink A, Alten R, Burmester G, Golder W, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Reddig J, Sieper J: Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthritis Rheum 2003;48:2224-2233
  61. Braun J, Brandt J, Listing J, Zink A, Alten R, Burmester G, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Sieper J: Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis. Ann Rheum Dis 2005;64:229-234
  62. Braun J, Baraliakos X, Brandt J, Listing J, Zink A, Alten R, Burmester G, Gromnica-Ihle E, Kellner H, Schneider M, Sorensen H, Zeidler H, Sieper J: Persistent clinical response to the anti-TNF-alpha antibody infliximab in patients with ankylosing spondylitis over 3 years. Rheumatology (Oxford) 2005;44:670-676
  63. van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, Braun J: Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005;52:582-591
  64. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, Dougados M, Reveille JD, Wong RL, Kupper H, DavisJC Jr: Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2006;54:2136-2146
  65. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J: Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 2008;58:3402-3412
  66. Tzelepis GE, Kalliakosta G, Tzioufas AG, Sfikakis PP, Mandros C, Boki KA, Roussos C, Moutsopoulos HM: Thoracoabdominal motion in ankylosing spondylitis: association with standardised clinical measures and response to therapy. Ann Rheum Dis 2009;68:966-971
  67. Braun J, Baraliakos X, Listing J, Sieper J: Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum 2005;52:2447-2451
  68. Baraliakos X, Listing J, Rudwaleit M, Brandt J, Alten R, Burmester G, Gromnica-Ihle E, Haibel H, Schewe S, Schneider M, Sorensen H, Zeidler H, Visvanathan S, Sieper J, Braun J: Safety and efficacy of readministration of infliximab after long-term continuous therapy and withdrawal in patients with ankylosing spondylitis. J Rheumatol 2007;34:510-515
  69. Kvien TK, Heiberg, Lie E, Kaufmann C, Mikkelsen K, Nordvåg BY, Rødevand E: A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases. Clin Exp Rheumatol 2005;23:(suppl 39)S188-S194
  70. Heiberg MS, Koldingsnes W, Mikkelsen K, Rødevand E, Kaufmann C, Mowinckel P, Kvien TK: The comparative one-year performance of antitumor necrosis factor alpha drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: results from a longitudinal, observational, multicenter study. Arthritis Rheum 2008;59:234-240
  71. Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, Li S, Dooley LT, Griffiths CE: Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005;366:1367-1374
  72. Feldman SR, Gordon KB, Bala M, Evans R, Li S, Dooley LT, Guzzo C, Patel K, Menter A, Gottlieb AB: Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial. Br J Dermatol 2005;152:954-960
  73. Antoni C, Krueger GG, de VK, Birbara C, Beutler A, Guzzo C, Zhou B, Dooley LT, Kavanaugh A: Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis 2005;64:1150-1157
  74. Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, Sharp JT, Ory PA, Perdok RJ, Weinberg MA: Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:3279-3289
  75. Gordon KB, Langley RG, Leonardi C, Toth D, Menter MA, Kang S, Heffernan M, Miller B, Hamlin R, Lim L, Zhong J, Hoffman R, Okun MM: Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol 2006;55:598-606
  76. Gladman DD, Mease PJ, Ritchlin CT, Choy EH, Sharp JT, Ory PA, Perdok RJ, Sasso EH: Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial. Arthritis Rheum 2007;56:476-488
  77. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, Papp K, Zrubek J, Mudivarthy S, Mack M, Visvanathan S, Beutler A: Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009;60:976-986
  78. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ: Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356:385-390
  79. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, Salonen D, Rubenstein J, Sharp JT, Tsuji W: Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;50:2264-2272
  80. Gladman DD: Adalimumab, etanercept and infliximab are equally effective treatments for patients with psoriatic arthritis. Nat Clin Pract Rheumatol 2008;4:510-511
  81. Ritchlin CT, Kavanaugh A, Gladman DD, Mease PJ, Helliwell P, Boehncke WH, de Vlam K, Fiorentino D, Fitzgerald O, Gottlieb AB, McHugh N, Nash PT, Qureshi A, Soriano ER, Taylor WJ: Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 2008;Epub ahead of print
  82. Kyle S, Chandler D, Griffiths CE, Helliwell P, Lewis J, McInnes I, Oliver S, Symmons D, McHugh N: Guideline for anti-TNF-alpha therapy in psoriatic arthritis. Rheumatology (Oxford) 2005;44:390-397
  83. Boehncke WH, Brasie RA, Barker J, Chimenti S, Dauden E, de Rie M, Dubertret L, Giannetti A, Katsambas A, Kragballe K, Naeyaert JM, Ortonne JP, Peyri J, Prinz JC, Saurat JH, Strohal R, van de Kerkhof P, Sterry W: Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus. J Eur Acad Dermatol Venereol 2006;20:988-998
  84. Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R: Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008;58:826-850
  85. Paller AS, Siegfried EC, Langley RG, Gottlieb AB, Pariser D, Landells I, Hebert AA, Eichenfield LF, Patel V, Creamer K, Jahreis A: Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med 2008;358:241-251
  86. Targan S, Hanauer S, van Deventer S, Mayer L, Present D, Braakman T, DeWoody K, Schaible T, Rutgeerts P: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group: N Engl J Med 1997;337:1029-1035
  87. Lichtenstein GR, Yan S, Bala M, Blank M, Sands B: Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology 2005;128:862-869
  88. Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogez RA, Podolsky DK, Sands BE, Braakman T, DeWoody KL, Schaible TF, vanDeventer SJ: Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999;340:1398-1405
  89. Hyams JS, Crandall W, Kugathasan S, Heuschkel R, Griffiths A, Cohen S, Markowitz J, Olsen A, Johanns J, Baldassano R: A randomized, multicenter, openlabel study to evaluate the safety and efficacy of infliximab in pediatric patients with moderate-to-severe Crohn's disease (abstract). J Pediatr Gastroenterol Nutr 2005;41:539
  90. Papadakis KA, Shaye OA, Vasiliauskas EA, Ippoliti A, Dubinsky MC, Birt J, Paavola J, Lee SK, Price J, Targan SR, Abreu MT: Safety and efficacy of adalimumab (D2E7) in Crohn's disease patients with an attenuated response to infliximab. Am J Gastroenterol 2005;100:75-79
  91. Sandborn WJ, Hanauer SB, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh DG, Panaccione R, Wolf D, Kent JD, Bittle B, Li L, Pollack PF: Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut 2007;56:1232-1239
  92. Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, Bloomfield R, Schreiber S: PRECISE 1 Study Investigators: Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med 2007;357:228-238
  93. Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen Oø, Hanauer SB, McColm J, Bloomfield R, Sandborn WJ: PRECISE 2 Study Investigators: Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med 2007;357:239-250
  94. Feagan BG, Coteur G, Tan S, Keininger DL, Schreiber S: Clinically meaningful improvement in health-related quality of life in a randomized controlled trial of certolizumab pegol maintenance therapy for Crohn's disease. Am J Gastroenterol 2009;Epub ahead of print
  95. Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel JF: Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 2008;6:644-653
  96. Rispo A, Scarpa R, Di Girolamo E, Cozzolino A, Lembo G, Atteno M, De Falco T, Lo Presti M, Castiglione F: Infliximab in the treatment of extraintestinal manifestations of Crohn's disease. Scand J Rheumatol 2005;34:387-391
  97. Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, Forbes A, Greenwood R, Probert CS: Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 2006;55:505-509
  98. Sandborn WJ, Hanauer SB, Katz S, Safdi M, Wolf DG, Baerg RD, Tremaine WJ, Johnson T, Diehl NN, Zinsmeister AR: Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2001;121:1088-1094
  99. Probert CS, Hearing SD, Schreiber S, Kühbacher T, Ghosh S, Arnott ID, Forbes A: Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Gut 2003;52:998-1002
  100. Järnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlén P, Grännö C, Vilien M, Ström M, Danielsson A, Verbaan H, Hellström PM, Magnuson A, Curman B: Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005;128:1805-1811
  101. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476erratum in N Engl J Med 2006;354:2200
  102. Gonzalez-Lama Y, Fernandez-Blanco I, Lopez-SanRoman A, Taxonera C, Casis B, Tabernero S, Bermejo F, Martinez-Silva F, Mendoza JL, Martinez-Montiel P, Carneros JA, Sanchez F, Maté J, Gisbert JP: Group for the Study of Inflammatory Bowel Diseases from Madrid. Open-label infliximab therapy in ulcerative colitis: a multicenter survey of results and predictors of response. Hepatogastro-enterology 2008;55:1609-1614
  103. Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P, Markomichelakis NN: Effect of Infliximab on sight-threatening panuveitis in Behcet's disease. Lancet 2001;358:295-296
  104. Sfikakis PP, Kaklamanis P, Elezoglou A, Katsilambros N, Theodossiadis PG, Papaefthimiou S, Markomichelakis NN: Infliximab for recurrent sight-threatening ocular inflammation in Adamantiades-Behcet's disease. Ann Intern Med 2004;140:404-406
  105. Ohno S, Nakamura S, Hori S, Shimakawa M, Kawashima H, Mochizuki M, Sugita S, Ueno S, Yoshizaki K, Inaba G: Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behcet's disease with refractory uveoretinitis. J Rheumatol 2004;31:1362-1368
  106. Tugal-Tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu E, Inanc M, Gül A: Efficacy of Infliximab in the treatment of uveitis that is refractory to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behcet's disease: an open-label trial. Arthritis Rheum 2005;52:2478-2484
  107. Sfikakis PP: Behcet's disease: a new target for antitumor necrosis factor treatment. Ann Rheum Dis 2002;61:(suppl 2)ii51-ii53
  108. Sfikakis PP, Markomichelakis N, Alpsoy E, Assaad-Khalil S, Bodaghi B, Gul A, Ohno S, Pipitone N, Schirmer M, Stanford M, Wechsler B, Zouboulis C, Kaklamanis P, Yazici H: Anti-TNF therapy in the management of Behcet's disease - review and basis for recommendations. Rheumatology (Oxford) 2007;46:736-741
  109. Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul S, Hamuryudan V, Yazici H: Short-term trial of etanercept in Behcet's disease: a double blind, placebo controlled study. J Rheumatol 2005;32:98-105
  110. Theodossiadis PG, Markomichelakis NN, Sfikakis PP: Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina J Ret Vit Dis 2007;27:399-413
  111. Markomichelakis N, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfiakakis PP: Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 2004;138:648-650
  112. Sfikakis PP, Markomichelakis N, Theodossiadis GP, Grigoropoulos V, Katsilambros N, Theodossiadis PG: Regression of sight-threatening macular edema in type 2 diabetes following treatment with the antitumor necrosis factor monoclonal antibody Infliximab. Diabetes Care 2005;28:445-447
  113. Markomichelakis N, Theodossiadis PG, Sfikakis PP: Regression of neovascular age-related macular degeneration following Infliximab therapy. Am J Ophthalmol 2005;139:537-540
  114. Theodossiadis PG, Liarakos VS, Sfikakis PP, Charonis A, Agrogiannis G, Kavantzas N, Vergados IA: Intravitreal administration of the anti-TNF monoclonal antibody Infliximab in the rabbit. Graefes Arch Clin Exp Ophtalmol 2009;247:273-281
  115. Theodossiadis PG, Liarakos VS, Sfikakis PP, Vergados IA, Theodossiadis GP: Intravitreal administration of the anti-TNF agent Infliximab for neovascular age-related macular degeneration. Am J Ophthalmol 2009;147:825-830
  116. Alexis AF, Strober BE: Off-label dermatologic uses of anti-TNF-α therapies. J Cutan Med Surg 2005;9:296-302
  117. Rigopoulos D, Korfitis C, Gregoriou S, Katsambas AD: Infliximab in dermatological treatment: beyond psoriasis. Expert Opin Biol Ther 2008;8:123-133
  118. Aringer M, Graninger WB, Steiner G, Smolen JS: Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an openlabel study. Arthritis Rheum 2004;50:3161-3169
  119. Lionaki S, Siamopoulos K, Theodorou I, Papadimitraki E, Bertsias G, Boumpas D, Boletis J: Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study. Nephrol Dial Transplant 2009;24:2144-2150
  120. Mastrandrea L, Yu J, Behrens T, Buchlis J, Albini C, Fourtner S, Quattrin T: Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study. Diabetes Care 2009;32:1244-1249
  121. Denton CP, Engelhart M, Tvede N, Wilson H, Khan K, Shiwen X, Carreira PE, Diaz Gonzalez F, Black CM, van den Hoogen FH: An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Ann Rheum Dis 2008;Epub ahead of print
  122. Efthimiou P, Schwartzman S, Kagen LJ: Possible role for tumour necrosis factor inhibitors in the treatment of resistant dermatomyositis and polymyositis: a retrospective study of eight patients. Ann Rheum Dis 2006;65:1233-1236
  123. Dastmalchi M, Grundtman C, Alexanderson H, Mavragani CP, Einarsdottir H, Helmers SB, Elvin K, Crow MK, Nennesmo I, Lundberg IE: A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies. Ann Rheum Dis 2008;67:1670-1677
  124. Riley P, McCann LJ, Maillard SM, Woo P, Murray KJ, Pilkington CA: Effectiveness of infliximab in the treatment of refractory juvenile dermatomyositis with calcinosis. Rheumatology (Oxford) 2008;47:877-880
  125. Kokkinos A, Iliopoulos A, Greka P, Efthymiou A, Katsilambros N, Sfikakis PP: Successful treatment of refractory adult-onset Still's disease with infliximab. A prospective, non-comparative series of four patients. Clin Rheumatol 2004;23:45-49
  126. Fautrel B, Sibilia J, Mariette X, Combe B: Club Rhumatismes et Inflammation: Tumour necrosis factor alpha blocking agents in refractory adult Still's disease: an observational study of 20 cases. Ann Rheum Dis 2005;64:262-266
  127. Saint Marcoux B, De Bandt M: CRI (Club Rhumatismes et Inflammation): Vasculitides induced by TNFalpha antagonists: a study in 39 patients in France. Joint Bone Spine 2006;73:710-713
  128. Lamprecht P, Till A, Steinmann J, Aries PM, Gross WL: Current state of biologicals in the management of systemic vasculitis. Ann N Y Acad Sci 2007;1110:261-270
  129. Utz JP, Limper AH, Kalra S, Specks U, Scott JP, Vuk-Pavlovic Z, Schroeder DR: Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest 2003;124:177-185
  130. Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, Muller-Quernheim J, Schlenker-Herceg R, Flavin S, Lo KH, Oemar B, Barnathan ES: Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 2006;174:795-802
  131. Mariette X, Ravaud P, Steinfeld S, Baron G, Goetz J, Hachulla E, Combe B, Puéchal X, Pennec Y, Sauvezie B, Perdriger A, Hayem G, Janin A, Sibilia J: Inefficacy of infliximab in primary Sjögren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren's Syndrome (TRIPSS). Arthritis Rheum 2004;50:1270-1276
  132. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group: Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005;352:351-361
  133. Cohen S, Shoup A, Weisman MH, Harris J: Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol 2005;26:903-907
  134. Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, Mahler D, Saadeh C, Siler T, Snell P, Korenblat P, Smith W, Kaye M, Mandel M, Andrews C, Prabhu R, Donohue JF, Watt R, Lo KH, Schlenker-Herceg R, Barnathan ES, Murray J, COPD Investigators: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007;175:926-934
  135. Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Bowman C, Hammond A, Kirkham B, Järvinen S, Niinimäki J, Veeger N, Haapea M, Torkki M, Tervonen O, Seitsalo S, Hurri H: The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial. Spine 2006;31:2759-2766
  136. Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL: Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 2009;110:1116-1126
  137. Hoffman GS, Cid MC, Rendt-Zagar KE, Merkel PA, Weyand CM, Stone JH, Salvarani C, Xu W, Visvanathan S, Rahman MU: Infliximab-GCA Study Group: Infliximab for maintenance of gluco-corticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann Intern Med 2007;146:621-630
  138. Salvarani C, Macchioni P, Manzini C, Paolazzi G, Trotta A, Manganelli P, Cimmino M, Gerli R, Catanoso MG, Boiardi L, Cantini F, Klersy C, Hunder GG: Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med 2007;146:631-639
  139. Rossman MD, Newman LS, Baughman RP, Teirstein A, Weinberger SE, Miller W Jr, Sands BE: A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2006;23:201-208
  140. Baughman RP, Lower EE, Drent M: Inhibitors of tumor necrosis factor (TNF) in sarcoidosis: who, what, and how to use them. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:76-89
  141. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group: TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 1999;53:457-465
  142. van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, von Blomberg BM, Woody JN, Hartung HP, Polman CH: Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 1996;47:1531-1534
  143. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, Djian J, Drexler H, Feldman A, Kober L, Krum H, Liu P, Nieminen M, Tavazzi L, van Veldhuisen DJ, Waldenstrom A, Warren M, Westheim A, Zannad F, Fleming T: Targeted anticy-tokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004;109:1594-1602
  144. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT: Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003;107:3133-3140
  145. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, Rahman MU: The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. Arthritis Rheum 2006;54:1075-1086
  146. Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M, Gromnica-Ihle E, Antoni C, Herzer P, Kekow J, Schneider M, Zink A: Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 2005;52:3403-3412
  147. Dixon W, Watson K, Lunt M, Hyrich KL, Silman AJ, Symmons DP: British Society for Rheumatology Biologics Register: Rates of serious infections, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-TNF therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2006;54:2368-2376
  148. Nathan DM, Angus PW, Gibson PR: Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol 2006;21:1366-1371
  149. Cepeda EJ, Williams FM, Ishimori ML, Weisman MH, Reveille JD: The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease. Ann Rheum Dis 2008;67:710-712
  150. Wallis RS, Kyambadde P, Johnson JL, Horter L, Kittle R, Pohle M, Ducar C, Millard M, Mayanja-Kizza H, Whalen C, Okwera A: A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 2004;18:257-264
  151. Ramos-Casals M, Brito-Zerón P, Muñoz S, Soria N, Galiana D, Bertolaccini L, Cuadrado MJ, Khamashta MA: Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 2007;86:242-251
  152. Williams E, Gadola S, Edwards CJ: Anti-TNF-induced lupus. Rheumatology (Oxford) 2009;48:716-720
  153. Eriksson C, Engstrand S, Sundqvist KG, Rantapaa-Dahlqvist S: Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha. Ann Rheum Dis 2005;64:403-407
  154. Elezoglou A, Kafasi N, Kaklamanis PH, Theodossiadis PG, Kapsimali V, Choremi E, Vaiopoulos G, Sfikakis PP: Infliximab treatment-induced formation of autoantibodies is common in Bechet's disease. Clin Exp Rheumatol 2007;25:(suppl 45)S65-S69
  155. Caramaschi P, Bambara LM, Pieropan S, Tinazzi I, Volpe A, Biasi D: Anti-TNF alpha blockers, autoantibodies and autoimmune disease. Join Bone Spine 2009;76:333-342
  156. Symmons DPM, Silman AJ: Anti-tumor necrosis factor therapy and the risk of lymphoma in rheumatoid arthritis: no clear answer. Arthritis Rheum 2004;50:1703-1706
  157. Keystone EC: Safety of biologic therapies-an update. J Rheumatol Suppl 2005;74:8-12
  158. Setoguchi S, Solomon DH, Weinblatt ME, Katz JN, Avorn J, Glynn RJ, Cook EF, Carney G, Schneeweiss S: Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:2757-2764
  159. Nannini C, Cantini F, Niccoli L, Cassarà E, Salvarani C, Olivieri I, Lally EV: Single-center series and systematic review of randomized controlled trials of malignancies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis receiving anti-tumor necrosis factor alpha therapy: is there a need for more comprehensive screening procedures?. Arthritis Rheum 2009;61:801-812
  160. Burmester GR, Mease PJ, Dijkmans BA, Gordon K, Lovell D, Panaccione R, Perez J, Pangan AL: Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis 2009;Epub ahead of print
  161. Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO: Granulomatus infectious diseases associated with TNF antagonists. Clin Infect Dis 2004;38:1261-1265correction Clin Infect Dis 2004;39:1254-1255
  162. Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M, Pallot-Prades B, Pouplin S, Sacchi A, Chichemanian RM, Bretagne S, Emilie D, Lemann M, Lorthololary O, Mariette X: Research Axed on Tolerance of Biotherapies Group: Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French research axed on tolerance of biotherapies registry. Arthritis Rheum 2009;60:1884-1894
  163. Wallis RS: Tumor necrosis factor antagonists: structure, function and tuberculosis risks. Lancet Infect dis 2008;8:601-611
  164. Furst DE, Wallis RS, Broder M, Beenhouwer DO: Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. Semin Arthritis Rheum 2006;36:159-167
  165. Saliu OY, Sofer C, Stein DS, Schwander SK, Wallis RS: Tumor necrosis factor blockers: differential effects on mycobacterial immunity. J Infect Dis 2006;194:486-492
  166. Iliopoulos A, Psathakis K, Aslanidis S, Skagias L, Sfikakis PP: Tuberculosis and granuloma formation in patients receiving anti-TNF therapy. Int J Tuberc Lung Dis 2006;10:588-590
  167. Gomez-Reino JJ, Carmona L, AngelDescalzo M: Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection. Arthritis Rheum 2007;57:756-761
  168. Sfikakis PP, Iliopoulos A, Elezoglou A, Kittas C, Stratigos A: Psoriasis induced by anti-TNF therapy: a paradoxical adverse reaction. Arthritis Rheum 2005;52:2513-2518
  169. Stratigos AJ, Sfikakis PP: Psoriasis occurring during anti-TNF therapy: causal effect or unrelated ?. Future Rheumatol 2006;1:281-284
  170. Ko JM, Gottlieb AB, Kerbleski JF: Induction and exacerbation of psoriasis with TNF-blockade therapy: a review and analysis of 127 cases. J Dermatolog Treat 2009;20:100-108
  171. Moustou AE, Matekovits A, Dessinioti C, Antoniou C, Sfikakis PP, Stratigos AJ: Side effects of biologic anti-TNF therapy: a clinical review. J Am Acad Dermatol 2009;Epub ahead of print
  172. Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, Hyrich KL, Symmons DP: Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2009;68:209-215
  173. Michaelsson G, Kajermo U, Michaelsson A, Hagforsen E: Infliximab can precipitate as well as worsen palmoplantar pustulosis: possible linkage to the expression of tumour necrosis factor alpha in the normal palmar eccrine sweat duct?. Br J Dermatol 2005;153:1243-1244
  174. Saint Marcoux B, De bandt M: CRI (Club Rhumatismes et Inflammation): Vasculitides induced by TNFalpha antagonists. Joint Bone Spine 2006;76:710-713
  175. Massara A, Cavazzini L, La Corte R, Trotta F: Sarcoidosis appearing during anti-tumor necrosis factor alpha therapy: a new ‘class effect’ paradoxical phenomenon. Two case reports and literature review. Semin Arthritis Rheum 2009;Epub ahead of print
  176. Hyrich KL, Watson KD, Silman AJ, Symmons DP: British Society for Rheumatology Biologics Register: Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford) 2006;45:1558-1565
  177. Esters N, Vermeire S, Joossens S, Noman M, Louis E, Belaiche J, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, Poulain D, Bossuyt X, Rutgeerts P: Belgian Group of Infliximab Expanded Access Program in Crohn's Disease: Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease. Am J Gastroenterol 2002;97:1458-1462
  178. Bruns A, Nicaise-Roland P, Hayem G, Palazzo E, Dieudé P, Grootenboer-Mignot S, Chollet-Martin S, Meyer O: Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis. Joint Bone Spine 2009;76:248-253
  179. Hueber W, Tomooka BH, Batliwalla F, Li W, Monach PA, Tibshirani RJ, Van Vollenhoven RF, Lampa J, Saito K, Tanaka Y, Genovese MC, Klareskog L, Gregersen PK, Robinson WH: Blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis. Arthritis Res Ther 2009;11:R76
  180. Wong M, Ziring D, Korin Y, Desai S, Kim S, Lin J, Gjertson D, Braun J, Reed E, Singh RR: TNFα blockade in human diseases: mechanisms and future directions. Clin Immunol 2008;126:121-136
  181. Kollias G, Kontoyiannis D: Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatment. Cytokine Growth Factor Rev 2002;13:315-321
  182. Alexopoulou L, Kranidioti K, Xanthoulea S, Denis M, Kotanidou A, Douni E, Blackshear PJ, Kontoyiannis DL, Kollias G: Transmembrane TNF protects mutant mice against intracellular bacterial infections, chronic inflammation and autoimmunity. Eur J Immunol 2006;36:2768-2780

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50