Skip to main content
SpringerLink
Log in

Traditional Systemic Therapy I: Methotrexate and Cyclosporine

  • Chapter
  • First Online:
Advances in Psoriasis

  • 1211 Accesses

Abstract

This chapter will review the traditional systemic drugs, methotrexate and cyclosporine, both of which are used in treating patients with moderate to severe psoriasis or recalcitrant psoriasis. Systemic therapies are also used in patients with psoriatic arthritis and disease not amenable to topical or light therapy. Methotrexate, a folic acid analogue, has become “the gold standard” of systemic therapies for moderate to severe psoriasis. It is often the initial systemic therapy started and has become the most widely used. Cyclosporine, a T-cell inhibitor that downregulates IL-2, is highly effective and highly efficient. It is often used in short durations when rapid control is desired. The pharmacology and use of these drugs in the treatment of patients with psoriasis will be covered as well as the parameters to screen patients, monitoring guidelines and adverse effects associated with each.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735–41.

    Article  CAS  PubMed  Google Scholar 

  2. Takahashi H, Iizuka H. Psoriasis and metabolic syndrome. J Dermatol. 2012;39:212–18.

    Article  CAS  PubMed  Google Scholar 

  3. Myers WA, Gottliep AB, Maase P. Psoriasis and psoriatic arthritis: clinical features and disease mechanism. Clin Dermatol. 2006;24:438–47.

    Article  PubMed  Google Scholar 

  4. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol. 1995;32:982–6.

    Article  CAS  PubMed  Google Scholar 

  5. Neimann AL, Shin DB, Wang X, et al. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55:829–35.

    Article  PubMed  Google Scholar 

  6. Mallbis L, Ritchen CT, Stahl M. Metabolic disorders in patients with psoriasis and psoriatic arthritis. Curr Rheumatol Rep. 2006;8:355–63.

    Article  Google Scholar 

  7. Kalb RE, Strober B, Weinstein G, et al. Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference. J Am Acad Dermatol. 2009;60:824–37.

    Article  PubMed  Google Scholar 

  8. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb AB, Koo JY, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61(3):451–85.

    Article  CAS  PubMed  Google Scholar 

  9. Gubner R, August S, Ginsberg V. Therapeutic suppression of tissue reactivity: effects of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci. 1951;221:176–82.

    Article  CAS  PubMed  Google Scholar 

  10. Edmunson WF, Guy WB. Treatment of psoriasis with folic acid antagonists. AMA Arch Derm. 1958;78:200–3.

    Article  Google Scholar 

  11. Weinstein GD. Methotrexate. Ann Intern Med. 1977;86:199–204.

    Article  CAS  PubMed  Google Scholar 

  12. Weinstein GD, Frost P. Methotrexate for psoriasis. A new therapeutic schedule. Arch Dermatol. 1971;103:33–8.

    Article  CAS  PubMed  Google Scholar 

  13. Warren RB, Griffiths EM. Systemic therapies for psoriasis: methotrexate, retinoids, and cyclosporine. Clin Dermatol. 2008;26:438–47.

    Article  PubMed  Google Scholar 

  14. Carrerero G, Puig L, Dehesa L, Carrascosa J, Ribera M, Sanchez-Regana M, Dauden E, Vidal D, Alsina M, Munoz-Santos C, Lopez-Estebaranz J, Notario J, Ferrandiz C, Vanaclocha F, Garcia-Bustinduy M, Taberner R, Belinchon I, Sanchez-Carazo J, Noreno J, Psoriasis Group of the Spanish Academy of Dermatology and Venereology. Guidelines on the use of methotrexate in psoriasis. Actas Dermosifiliogr. 2010;101:600–13.

    Article  Google Scholar 

  15. Strober B, Menon B. Folate supplementation during methotrexate therapy for patients with psoriasis. J Am Acad Dermatol. 2005;53:652–9.

    Article  PubMed  Google Scholar 

  16. Cronstein BN, Naime D, Ostad E. The anti-inflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an vivo and in vitro model of inflammation. J Clin Invest. 1993;92:2675–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J Clin Invest. 1998;102:322–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Johnston A, Gudjonsson JF, Sigmundsdottir H, Ludviksson BR, Valdimarsson H. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005;114:154–63.

    Article  CAS  PubMed  Google Scholar 

  19. Roenigk Jr HH, Maibach HI, Weinstein GP. Methotrexate therapy for psoriasis. Guideline revisions. Arch Dermatol. 1973;108:35.

    Article  PubMed  Google Scholar 

  20. Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis, section 2: Psoriatic arthritis; overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58:851–64.

    Article  PubMed  Google Scholar 

  21. Montaudié H, Sbidian E, Paul C, Maza A, Gallini A, Aractingi S, Aubin F, Bachelez H, Cribier B, Joly P, Jullien D, Le Maître M, Misery L, Richard M, Ortonne J. Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity. J Eur Acad Dermatol Venereol. 2011;25 Suppl 2:12–8.

    Article  PubMed  Google Scholar 

  22. Roenigk HH, Auerbach R, Maibach H, Weinstein G, Lebwohl M. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol. 1998;38:473–85.

    Article  Google Scholar 

  23. Chalmers RJ, Kirby B, Smith A, Burrows P, Little R, Horan M, et al. Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicenter audit and health economic analysis. Br J Dermatol. 2005;152:444–50.

    Article  CAS  PubMed  Google Scholar 

  24. Shiroky JB, Neville C, Esdaile JM, Choquette D, Zummer M, Hazeltine M, Bykerk V, Kanji M, St Pierre A, Robidoux L, et al. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1993;36(6):795–803.

    Article  CAS  PubMed  Google Scholar 

  25. Mueller W, Hermann B. Cyclosporine A for psoriasis. N Engl J Med. 1979;301:555.

    CAS  PubMed  Google Scholar 

  26. Maza A, Montaudié H, Sbidian E, Gallini A, Aractingi S, Aubin F, Bachelez H, Cribier B, Joly P, Jullien D, Le Maître M, Misery L, Richard MA, Ortonne J-P, Paul C. Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis. J Eur Assoc Dermatol Venereol. 2011;25(Supp 2):19–27.

    Article  CAS  Google Scholar 

  27. Rosmarin DM, Lebwohl M, Elewski B, Gottlieb A. Cyclosporine and psoriasis: 2008 National Psoriasis Foundation* Consensus Conference. J Am Acad Dermatol. 2010;62:838–53.

    Article  PubMed  Google Scholar 

  28. Marsland AM, Griffiths CE. The macrolide immunosuppressants in dermatology: mechanisms of action. Eur J Dermatol. 2002;12:618–22.

    CAS  PubMed  Google Scholar 

  29. Haider AS, Lowes MA, Suarez-Farinas M, Zaba LC, Cardinale I, Khatcherian A, et al. Identification of cellular pathways of “type 1”, Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008;180:1913–20.

    Article  CAS  PubMed  Google Scholar 

  30. Singh AK, Narsipur SS. Cyclosporine: a commentary on brand versus generic formulation exchange. J Transplant. 2011;2011:1–6.

    Article  Google Scholar 

  31. Brunner LJ, Pai KS, Munar MY, Lande MB, Olyaei AJ, Mowry JA. Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients. Pediatr Transplant. 2000;4:313–21.

    Article  CAS  PubMed  Google Scholar 

  32. Heydendael VM, Spuls PI, Opmeer BC, de Borgie CA, Reitsma JB, Goldschmidt WF, et al. Methotrexate versus cyclosporine in moderate-to-severe chronic plaque psoriasis. N Engl J Med. 2003;349:658–65.

    Article  CAS  PubMed  Google Scholar 

  33. Mahrle G, Schulze HJ, Farber L, Weidinger G, Steigleder GK. Low-dose short-term cyclosporine versus etretinate in psoriasis: improvement of skin, nail, and joint involvement. J Am Acad Dermatol. 1995;32:78–88.

    Article  CAS  PubMed  Google Scholar 

  34. Ho VC, Griffiths CE, Albrecht G, Vanaclocha F, Leon-Dorantes G, Atakan N, et al. Intermittent short courses of cyclosporin (Neoral(R)) for psoriasis unresponsive to topical therapy: a 1-year multicenter, randomized study: the PISCES study group. Br J Dermatol. 1999;141:283–91.

    Article  CAS  PubMed  Google Scholar 

  35. Ho VC, Griffiths CE, Berth-Jones J, Papp KA, Vanaclocha F, Dauden E, et al. Intermittent short courses of cyclosporine microemulsion for the long-term management of psoriasis: a 2-year cohort study. J Am Acad Dermatol. 2001;44:643–51.

    Article  CAS  PubMed  Google Scholar 

  36. Bae Y-S, Van Voorhees AS, Hui S, Korman NJ, Lebwohl MG, Young M, Bebo B, Kimball AB. Review of treatment options for psoriasis in pregnant or lactating women: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67(3):459–77.

    Article  PubMed  Google Scholar 

  37. Shupack J, Abel E, Bauer E, Brown M, Drake L, Freinkel R, et al. Cyclosporine as maintenance therapy in patients with severe psoriasis. J Am Acad Dermatol. 1997;36:423–32.

    Article  CAS  PubMed  Google Scholar 

  38. Silverberg NB. Pediatric psoriasis: an update. Ther Clin Risk Manag. 2009;5:849–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Marcil I, Stern RS. Squamous-cell cancer of the skin in patients given PUVA and cyclosporin: nested cohort cross-over study. Lancet. 2001;358:1042–5.

    Article  CAS  PubMed  Google Scholar 

  40. Leenen FH, Coletta E, Davies RA. Prevention of renal dysfunction and hypertension by amlodipine after heart transplant. Am J Cardiol. 2007;100:531–5.

    Article  CAS  PubMed  Google Scholar 

  41. Venkat-Raman G, Feehally J, Elliott HL, Griffin P, Moore RJ, Olubodun JO, Wilkinson R. Renal and haemodynamic effects of amlodipine and nifedipine in hypertensive renal transplant recipients. Nephrol Dial Transplant. 1999;14:384–8.

    Article  CAS  PubMed  Google Scholar 

  42. Isles CG, Stirling CM. Rhabdomyolysis due to simvastatin in a transplant patient: are some statins safer than others? Nephrol Dial Transplant. 2001;16:873–4.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Tulane University Health Sciences Center, 1430 Tulane Avenue #8036, New Orleans, LA, 70112, USA

    Robert M. Bacigalupi MD & Erin Boh MD, PhD

Authors
  1. Robert M. Bacigalupi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erin Boh MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erin Boh MD, PhD .

Editor information

Editors and Affiliations

  1. St. Luke's -Roosevelt Hospital Center, New York, New York, USA

    Jeffrey M. Weinberg

  2. Department of Dermatology, Icahn School of Medicine, New York, New York, USA

    Mark Lebwohl

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Bacigalupi, R.M., Boh, E. (2014). Traditional Systemic Therapy I: Methotrexate and Cyclosporine. In: Weinberg, J., Lebwohl, M. (eds) Advances in Psoriasis. Springer, London. https://doi.org/10.1007/978-1-4471-4432-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4432-8_10

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4431-1

  • Online ISBN: 978-1-4471-4432-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation