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. 2005 Mar;64(Suppl 2):ii78–ii82. doi: 10.1136/ard.2004.034157

Psoriatic arthritis treatment: biological response modifiers

P Mease, C Antoni
PMCID: PMC1766864  PMID: 15708944

Abstract

In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules.

Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA.

Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals.

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Selected References

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  1. Abrams J. R., Lebwohl M. G., Guzzo C. A., Jegasothy B. V., Goldfarb M. T., Goffe B. S., Menter A., Lowe N. J., Krueger G., Brown M. J. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999 May;103(9):1243–1252. doi: 10.1172/JCI5857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ali Yousaf, Shah Samir. Infliximab-induced systemic lupus erythematosus. Ann Intern Med. 2002 Oct 1;137(7):625–626. doi: 10.7326/0003-4819-137-7-200210010-00030. [DOI] [PubMed] [Google Scholar]
  3. Antoni Christian, Dechant Claudia, Hanns-Martin Lorenz P. D., Wendler Joerg, Ogilvie Alexandra, Lueftl Mathias, Kalden-Nemeth Dolores, Kalden Joachim R., Manger Bernhard. Open-label study of infliximab treatment for psoriatic arthritis: clinical and magnetic resonance imaging measurements of reduction of inflammation. Arthritis Rheum. 2002 Oct 15;47(5):506–512. doi: 10.1002/art.10671. [DOI] [PubMed] [Google Scholar]
  4. Baert Filip, Noman Maja, Vermeire Severine, Van Assche Gert, D' Haens Geert, Carbonez An, Rutgeerts Paul. Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease. N Engl J Med. 2003 Feb 13;348(7):601–608. doi: 10.1056/NEJMoa020888. [DOI] [PubMed] [Google Scholar]
  5. Bathon J. M., Martin R. W., Fleischmann R. M., Tesser J. R., Schiff M. H., Keystone E. C., Genovese M. C., Wasko M. C., Moreland L. W., Weaver A. L. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000 Nov 30;343(22):1586–1593. doi: 10.1056/NEJM200011303432201. [DOI] [PubMed] [Google Scholar]
  6. Beauparlant P., Papp K., Haraoui B. The incidence of cancer associated with the treatment of rheumatoid arthritis. Semin Arthritis Rheum. 1999 Dec;29(3):148–158. doi: 10.1016/s0049-0172(99)80026-2. [DOI] [PubMed] [Google Scholar]
  7. Ben-Chetrit E., Backenroth R. Amyloidosis induced, end stage renal disease in patients with familial Mediterranean fever is highly associated with point mutations in the MEFV gene. Ann Rheum Dis. 2001 Feb;60(2):146–149. doi: 10.1136/ard.60.2.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheifetz Adam, Smedley Michelle, Martin Sara, Reiter Monica, Leone Grace, Mayer Lloyd, Plevy Scott. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol. 2003 Jun;98(6):1315–1324. doi: 10.1111/j.1572-0241.2003.07457.x. [DOI] [PubMed] [Google Scholar]
  9. Chung Eugene S., Packer Milton, Lo Kim Hung, Fasanmade Adedigbo A., Willerson James T., Anti-TNF Therapy Against Congestive Heart Failure Investigators 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 Jun 9;107(25):3133–3140. doi: 10.1161/01.CIR.0000077913.60364.D2. [DOI] [PubMed] [Google Scholar]
  10. Dayer Jean-Michel. The saga of the discovery of IL-1 and TNF and their specific inhibitors in the pathogenesis and treatment of rheumatoid arthritis. Joint Bone Spine. 2002 Mar;69(2):123–132. doi: 10.1016/s1297-319x(02)00363-9. [DOI] [PubMed] [Google Scholar]
  11. Debandt M., Vittecoq O., Descamps V., Le Loët X., Meyer O. Anti-TNF-alpha-induced systemic lupus syndrome. Clin Rheumatol. 2003 Feb;22(1):56–61. doi: 10.1007/s10067-002-0654-5. [DOI] [PubMed] [Google Scholar]
  12. Devos S. A., Van Den Bossche N., De Vos M., Naeyaert J. M. Adverse skin reactions to anti-TNF-alpha monoclonal antibody therapy. Dermatology. 2003;206(4):388–390. doi: 10.1159/000069965. [DOI] [PubMed] [Google Scholar]
  13. Flynn J. L., Chan J. Immunology of tuberculosis. Annu Rev Immunol. 2001;19:93–129. doi: 10.1146/annurev.immunol.19.1.93. [DOI] [PubMed] [Google Scholar]
  14. 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. 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, 2004. Ann Rheum Dis. 2004 Nov;63 (Suppl 2):ii2–ii12. doi: 10.1136/ard.2004.029272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Genovese Mark C., Bathon Joan M., Martin Richard W., Fleischmann Roy M., Tesser John R., Schiff Michael H., Keystone Edward C., Wasko Mary Chester, Moreland Larry W., Weaver Arthur L. Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum. 2002 Jun;46(6):1443–1450. doi: 10.1002/art.10308. [DOI] [PubMed] [Google Scholar]
  16. Keane J., Gershon S., Wise R. P., Mirabile-Levens E., Kasznica J., Schwieterman W. D., Siegel J. N., Braun M. M. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001 Oct 11;345(15):1098–1104. doi: 10.1056/NEJMoa011110. [DOI] [PubMed] [Google Scholar]
  17. Klapman Jason B., Ene-Stroescu Daniel, Becker Michael A., Hanauer Stephen B. A lupus-like syndrome associated with infliximab therapy. Inflamm Bowel Dis. 2003 May;9(3):176–178. doi: 10.1097/00054725-200305000-00005. [DOI] [PubMed] [Google Scholar]
  18. Kraan Maarten C., van Kuijk Arno W. R., Dinant Huibert J., Goedkoop Amber Y., Smeets Tom J. M., de Rie Menno A., Dijkmans Ben A. C., Vaishnaw Akshay K., Bos Jan D., Tak Paul P. Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis. Arthritis Rheum. 2002 Oct;46(10):2776–2784. doi: 10.1002/art.10543. [DOI] [PubMed] [Google Scholar]
  19. Kremer Joel M., Westhovens Rene, Leon Marc, Di Giorgio Eduardo, Alten Rieke, Steinfeld Serge, Russell Anthony, Dougados Maxime, Emery Paul, Nuamah Isaac F. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003 Nov 13;349(20):1907–1915. doi: 10.1056/NEJMoa035075. [DOI] [PubMed] [Google Scholar]
  20. Kruithof E., Van den Bosch F., Baeten D., Herssens A., De Keyser F., Mielants H., Veys E. M. Repeated infusions of infliximab, a chimeric anti-TNFalpha monoclonal antibody, in patients with active spondyloarthropathy: one year follow up. Ann Rheum Dis. 2002 Mar;61(3):207–212. doi: 10.1136/ard.61.3.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lebwohl Mark, Christophers Enno, Langley Richard, Ortonne Jean P., Roberts Janet, Griffiths Christopher E. M., Alefacept Clinical Study Group An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol. 2003 Jun;139(6):719–727. doi: 10.1001/archderm.139.6.719. [DOI] [PubMed] [Google Scholar]
  22. Lebwohl Mark, Tyring Stephen K., Hamilton Tiffani K., Toth Darryl, Glazer Scott, Tawfik Naji H., Walicke Patricia, Dummer Wolfgang, Wang Xiaolin, Garovoy Marvin R. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med. 2003 Nov 20;349(21):2004–2013. doi: 10.1056/NEJMoa030002. [DOI] [PubMed] [Google Scholar]
  23. Lipsky P. E., van der Heijde D. M., St Clair E. W., Furst D. E., Breedveld F. C., Kalden J. R., Smolen J. S., Weisman M., Emery P., Feldmann M. 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 Nov 30;343(22):1594–1602. doi: 10.1056/NEJM200011303432202. [DOI] [PubMed] [Google Scholar]
  24. Maini R. N., Breedveld F. C., Kalden J. R., Smolen J. S., Davis D., Macfarlane J. D., Antoni C., Leeb B., Elliott M. J., Woody J. N. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 1998 Sep;41(9):1552–1563. doi: 10.1002/1529-0131(199809)41:9<1552::AID-ART5>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  25. Maini R., St Clair E. W., Breedveld F., Furst D., Kalden J., Weisman M., Smolen J., Emery P., Harriman G., Feldmann M. 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. 1999 Dec 4;354(9194):1932–1939. doi: 10.1016/s0140-6736(99)05246-0. [DOI] [PubMed] [Google Scholar]
  26. Mann Douglas L., McMurray John J. V., Packer Milton, Swedberg Karl, Borer Jeffrey S., Colucci Wilson S., Djian Jacques, Drexler Helmut, Feldman Arthur, Kober Lars. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004 Mar 15;109(13):1594–1602. doi: 10.1161/01.CIR.0000124490.27666.B2. [DOI] [PubMed] [Google Scholar]
  27. McInnes Iain B., Gracie J. Alastair. Interleukin-15: a new cytokine target for the treatment of inflammatory diseases. Curr Opin Pharmacol. 2004 Aug;4(4):392–397. doi: 10.1016/j.coph.2004.04.003. [DOI] [PubMed] [Google Scholar]
  28. Mease P. J., Antoni C. E., Gladman D. D., Taylor W. J. Psoriatic arthritis assessment tools in clinical trials. Ann Rheum Dis. 2005 Mar;64 (Suppl 2):ii49–ii54. doi: 10.1136/ard.2004.034165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mease P. J., Goffe B. S., Metz J., VanderStoep A., Finck B., Burge D. J. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000 Jul 29;356(9227):385–390. doi: 10.1016/S0140-6736(00)02530-7. [DOI] [PubMed] [Google Scholar]
  30. Mease P. TNFalpha therapy in psoriatic arthritis and psoriasis. Ann Rheum Dis. 2004 Jul;63(7):755–758. doi: 10.1136/ard.2004.020719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mease Philip J., Kivitz Alan J., Burch Francis X., Siegel Evan L., Cohen Stanley B., Ory Peter, Salonen David, Rubenstein Joel, Sharp John T., Tsuji Wayne. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004 Jul;50(7):2264–2272. doi: 10.1002/art.20335. [DOI] [PubMed] [Google Scholar]
  32. Mohan N., Edwards E. T., Cupps T. R., Oliverio P. J., Sandberg G., Crayton H., Richert J. R., Siegel J. N. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum. 2001 Dec;44(12):2862–2869. doi: 10.1002/1529-0131(200112)44:12<2862::aid-art474>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  33. Mohan V. P., Scanga C. A., Yu K., Scott H. M., Tanaka K. E., Tsang E., Tsai M. M., Flynn J. L., Chan J. Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun. 2001 Mar;69(3):1847–1855. doi: 10.1128/IAI.69.3.1847-1855.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Moreland L. W., Schiff M. H., Baumgartner S. W., Tindall E. A., Fleischmann R. M., Bulpitt K. J., Weaver A. L., Keystone E. C., Furst D. E., Mease P. J. Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999 Mar 16;130(6):478–486. doi: 10.7326/0003-4819-130-6-199903160-00004. [DOI] [PubMed] [Google Scholar]
  35. Mullighan C. G., Heatley S., Lester S., Rischmueller M., Gordon T. P., Bardy P. G. Fas gene promoter polymorphisms in primary Sjögren's syndrome. Ann Rheum Dis. 2004 Jan;63(1):98–101. doi: 10.1136/ard.2003.006056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nikas Spyros N., Drosos Alexandros A. Onercept. Serono. Curr Opin Investig Drugs. 2003 Nov;4(11):1369–1376. [PubMed] [Google Scholar]
  37. Ritchlin Christopher T., Haas-Smith Sally A., Li Ping, Hicks David G., Schwarz Edward M. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003 Mar;111(6):821–831. doi: 10.1172/JCI16069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Robinson W. H., Genovese M. C., Moreland L. W. Demyelinating and neurologic events reported in association with tumor necrosis factor alpha antagonism: by what mechanisms could tumor necrosis factor alpha antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis? Arthritis Rheum. 2001 Sep;44(9):1977–1983. doi: 10.1002/1529-0131(200109)44:9<1977::AID-ART345>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  39. Shakoor Najia, Michalska Margaret, Harris Charlotte A., Block Joel A. Drug-induced systemic lupus erythematosus associated with etanercept therapy. Lancet. 2002 Feb 16;359(9306):579–580. doi: 10.1016/S0140-6736(02)07714-0. [DOI] [PubMed] [Google Scholar]
  40. Terslev L., Torp-Pedersen S., Qvistgaard E., Kristoffersen H., Røgind H., Danneskiold-Samsøe B., Bliddal H. Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography. Ann Rheum Dis. 2003 Feb;62(2):178–181. doi: 10.1136/ard.62.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Thorstensson C. A., Petersson I. F., Jacobsson L. T. H., Boegård T. L., Roos E. M. Reduced functional performance in the lower extremity predicted radiographic knee osteoarthritis five years later. Ann Rheum Dis. 2004 Apr;63(4):402–407. doi: 10.1136/ard.2003.007583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Weinblatt M. E., Kremer J. M., Bankhurst A. D., Bulpitt K. J., Fleischmann R. M., Fox R. I., Jackson C. G., Lange M., Burge D. J. 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 Jan 28;340(4):253–259. doi: 10.1056/NEJM199901283400401. [DOI] [PubMed] [Google Scholar]

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