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Current Dermatology Reports

, Volume 7, Issue 1, pp 52–58 | Cite as

Update on Oral Therapy for Psoriasis

  • Fernando ValenzuelaEmail author
  • Javier Fernández
  • Pablo Santa María
Psoriasis (Jaishin Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Psoriasis

Abstract

Purpose of Review

The aim of this review article is to summarize the information of oral treatments of psoriasis, with emphasis in new information and newer drugs.

Recent Findings

Methotrexate has an adequate efficacy and safety profile with low cost and large real-life evidence. Cyclosporine’s therapeutic power is abated by the long-term safety issues. Acitretin has a niche in special circumstances such as combination with phototherapy, HIV population, or special forms of psoriasis such as palmoplantar, pustular, and erythrodermic psoriasis. Apremilast, the newer available drug of this group demonstrates a modest but acceptable efficacy and good safety in this population. Other drugs have been evaluated with different results in this field.

Summary

Oral therapy for psoriasis is widely used in patients with moderate to severe disease; thus, it is crucial to know the latest information and indications as well as the recent development of new drugs.

Keywords

Methotrexate Cyclosporine Acitretin Apremilast Psoriasis 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Fernando Valenzuela declares consultancy for Pfizer, Novartis, and Janssen; expert testimony for Novartis, AbbVie, and Deutschepharma; and payment for development of educational presentations including service on sopeakers’ bureaus for Novartis, AbbVie, and Deutschepharma.

Drs. Javier Fernández and Pablo Santa María declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. 1.
    Aslam A, Griffiths CE. Drug therapies in dermatology. Clin Med (London, England). 2014;14(1):47–53.  https://doi.org/10.7861/clinmedicine.14-1-47.CrossRefGoogle Scholar
  2. 2.
    Torres T, Filipe P. Small molecules in the treatment of psoriasis. Drug Dev Res. 2015;76(5):215–27.  https://doi.org/10.1002/ddr.21263.CrossRefPubMedGoogle Scholar
  3. 3.
    Gooderham M. Small molecules: an overview of emerging therapeutic options in the treatment of psoriasis. Skin Ther Lett. 2013;18(7):1–4.Google Scholar
  4. 4.
    Palfreeman AC, McNamee KE, McCann FE. New developments in the management of psoriasis and psoriatic arthritis: a focus on apremilast. Drug Design Dev Ther. 2013;7:201–10.CrossRefGoogle Scholar
  5. 5.
    •• Nast A, Gisondi P, Ormerod AD, Saiag P, Smith C, Spuls PI, et al. European S3-Guidelines on the systemic treatment of psoriasis vulgaris—update 2015—short version—EDF in cooperation with EADV and IPC. J Eur Acad Dermatol Venereol: JEADV. 2015;29(12):2277–94. A recent evidence-based guidelines mandatory to psoriasis involved physicians.  https://doi.org/10.1111/jdv.13354.CrossRefPubMedGoogle Scholar
  6. 6.
    Menting SP, Dekker PM, Limpens J, Hooft L, Spuls PI. Methotrexate dosing regimen for plaque-type psoriasis: a systematic review of the use of test-dose, start-dose, dosing scheme, dose adjustments, maximum dose and folic acid supplementation. Acta Derm Venereol. 2016;96(1):23–8.  https://doi.org/10.2340/00015555-2081.CrossRefPubMedGoogle Scholar
  7. 7.
    •• West J, Ogston S, Foerster J. Safety and efficacy of methotrexate in psoriasis: a meta-analysis of published trials. PloS one. 2016;11(5):e0153740. Important information regarding methotrexate previous evidence.  https://doi.org/10.1371/journal.pone.0153740.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Nast A, Kopp I, Augustin M, Banditt KB, Boehncke WH, Follmann M, et al. German evidence-based guidelines for the treatment of psoriasis vulgaris (short version). Arch Dermatol Res. 2007;299(3):111–38.  https://doi.org/10.1007/s00403-007-0744-y.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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(1):78–88.  https://doi.org/10.1016/0190-9622(95)90189-2.CrossRefPubMedGoogle Scholar
  10. 10.
    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(7):658–65.  https://doi.org/10.1056/NEJMoa021359.CrossRefPubMedGoogle Scholar
  11. 11.
    Flytström I, Stenberg B, Svensson A, Bergbrant IM. Methotrexate vs cyclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br J Dermatol. 2008;158(1):116–21.  https://doi.org/10.1111/j.1365-2133.2007.08284.x.PubMedGoogle Scholar
  12. 12.
    Kragballe K, Jansen CT, Geiger JM, Bjerke JR, Falk ES, Gip L, et al. A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study. Actadermato-venereologica. 1989;69:35–40.Google Scholar
  13. 13.
    Gollnick H, Bauer R, Brindley C, Orfanos CE, Plewig G, Wokalek H, et al. Acitretin versus etretinate in psoriasis. Clinical and pharmacokinetic results of a German multicenter study. J Am Acad Dermatol. 1988;19(3):458–68.  https://doi.org/10.1016/S0190-9622(88)70198-X.CrossRefPubMedGoogle Scholar
  14. 14.
    Berbis P, Geiger JM, Vaisse C, Rognin C, Privat Y. Benefit of progressively increasing doses during the initial treatment with acitretin in psoriasis. Dermatologica. 1989;178(2):88–92.  https://doi.org/10.1159/000248398.CrossRefPubMedGoogle Scholar
  15. 15.
    Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. 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.  https://doi.org/10.1016/j.jaad.2009.03.027.CrossRefPubMedGoogle Scholar
  16. 16.
    • Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73:37–49. Pivotal study on apremilast and its use in psoriasis. CrossRefPubMedGoogle Scholar
  17. 17.
    Paul C, Cather J, Gooderham M, Poulin Y, Mrowietz U, Ferrandiz C, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173(6):1387–99.  https://doi.org/10.1111/bjd.14164.CrossRefPubMedGoogle Scholar
  18. 18.
    •• Warren RB, Mrowietz U, von Kiedrowski R, Niesmann J, Wilsmann-Theis D, Ghoreschi K, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:528–37. This study provides a well designed evidence on the use of subcutaneous methotrexate in moderate to severe plaque psoriasis CrossRefPubMedGoogle Scholar
  19. 19.
    Reich K, Langley RG, Papp KA, Ortonne JP, Unnebrink K, Kaul M, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med. 2011;365(17):1586–96.  https://doi.org/10.1056/NEJMoa1010858.CrossRefPubMedGoogle Scholar
  20. 20.
    Carrascosa JM, de la Cueva P, Ara M, Puig L, Bordas X, Carretero G, et al. Methotrexate in moderate to severe psoriasis: review of the literature and expert recommendations. Actas dermo-sifiliograficas. 2016;107(3):194–206.  https://doi.org/10.1016/j.ad.2015.10.005.CrossRefPubMedGoogle Scholar
  21. 21.
    • Otero ME, van den Reek JM, Seyger MM, van de Kerkhof PC, Kievit W, de Jong EM. Determinants for drug survival of methotrexate in patients with psoriasis, split according to different reasons for discontinuation: results of the prospective MTX-CAPTURE. Br J Dermatol. 2017;177:497–504. Relevant real life data in patients using methotrexate. CrossRefPubMedGoogle Scholar
  22. 22.
    West J, Ogston S, Palmer C, Fleming C, Dawe R, Kumar V, et al. Methotrexate in psoriasis under real-world conditions: long-term efficacy and tolerability. Br J Dermatol. 2016;174(6):1407–10.  https://doi.org/10.1111/bjd.14452.CrossRefPubMedGoogle Scholar
  23. 23.
    • Choi JH, Shin EJ, Shin MK, Kim NI. Immune parameters of Korean patients with psoriasis treated with low-dose cyclosporine. Ann Dermatol. 2017;29:111–3. This study provides a possible explanation about mechanism of action of low doses of cyclosporine. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Colombo D, Banfi G, Cassano N, Graziottin A, Vena GA, Fiori GG, et al. The GENDER ATTENTION Observational Study: gender and hormonal status differences in the incidence of adverse events during cyclosporine treatment in psoriatic patients. Adv Ther. 2017;34(6):1349–63.  https://doi.org/10.1007/s12325-017-0526-7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    • Davila-Seijo P, Dauden E, Carretero G, Ferrandiz C, Vanaclocha F, Gomez-Garcia FJ, et al. Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis. J Eur Acad Dermatol Venereol: JEADV. 2016;30:1942–50. Extensive real life evidence of Spanish psoriatic population and their treatment. PubMedGoogle Scholar
  26. 26.
    • Belinchon I, Ramos JM, Carretero G, Ferrandiz C, Rivera R, Dauden E, et al. Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm. J Eur Acad Dermatol Venereol : JEADV. 2017;31:1700–8. Another report of Spanish registry in psoriasis. CrossRefPubMedGoogle Scholar
  27. 27.
    Lee MS, Chang CH, Lin RY, Lai MS. Risks of hypertension associated with cyclosporine, nonsteroidal anti-inflammatory drugs, and systemic glucocorticoids in patients with psoriasis: a nationwide population-based nested case-control study in Taiwan. Pharmacoepidemiol Drug Saf. 2016;25(2):133–40.  https://doi.org/10.1002/pds.3890.CrossRefPubMedGoogle Scholar
  28. 28.
    Balmer JE, Blomhoff R. Gene expression regulation by retinoic acid. J Lipid Res. 2002;43(11):1773–808.  https://doi.org/10.1194/jlr.R100015-JLR200.CrossRefPubMedGoogle Scholar
  29. 29.
    Bauer R, Schutz R, Orfanos CE. Impaired motility and random migration of vital polymorphonuclears in vitro after therapy with oral aromatic retinoid in psoriasis. Int J Dermatol. 1984;23(1):72–7.  https://doi.org/10.1111/j.1365-4362.1984.tb05670.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Murray HE, Anhalt AW, Lessard R, Schacter RK, Ross JB, Stewart WD, et al. A 12-month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study. J Am Acad Dermatol. 1991;24(4):598–602.  https://doi.org/10.1016/0190-9622(91)70091-F.CrossRefPubMedGoogle Scholar
  31. 31.
    van de Kerkhof PC, Cambazard F, Hutchinson PE, Haneke E, Wong E, Souteyrand P, et al. The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin therapy in psoriasis. Br J Dermatol. 1998;138(1):84–9.  https://doi.org/10.1046/j.1365-2133.1998.02030.x.CrossRefPubMedGoogle Scholar
  32. 32.
    Dogra S, Yadav S. Acitretin in psoriasis: an evolving scenario. Int J Dermatol. 2014;53(5):525–38.  https://doi.org/10.1111/ijd.12365.CrossRefPubMedGoogle Scholar
  33. 33.
    Tanew A, Guggenbichler A, Honigsmann H, Geiger JM, Fritsch P. Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study. J Am Acad Dermatol. 1991;25(4):682–4.  https://doi.org/10.1016/0190-9622(91)70253-X.CrossRefPubMedGoogle Scholar
  34. 34.
    Lowe NJ, Prystowsky JH, Bourget T, Edelstein J, Nychay S, Armstrong R. Acitretin plus UVB therapy for psoriasis. Comparisons with placebo plus UVB and acitretin alone. J Am Acad Dermatol. 1991;24(4):591–4.  https://doi.org/10.1016/0190-9622(91)70089-K.CrossRefPubMedGoogle Scholar
  35. 35.
    White SI, Marks JM, Shuster S. Etretinate in pustular psoriasis of palms and soles. Br J Dermatol. 1985;113(5):581–5.  https://doi.org/10.1111/j.1365-2133.1985.tb02382.x.CrossRefPubMedGoogle Scholar
  36. 36.
    Foged E, Holm P, Larsen PO, Laurberg G, Reymann F, Roesdahle K, et al. A randomized trial of etretinate (Tigason) in palmoplantar pustulosis. Dermatologica. 1983;166(4):220–3.  https://doi.org/10.1159/000249872.CrossRefPubMedGoogle Scholar
  37. 37.
    Ozawa A, Ohkido M, Haruki Y, Kobayashi H, Ohkawara A, Ohno Y, et al. Treatments of generalized pustular psoriasis: a multicenter study in Japan. J Dermatol. 1999;26(3):141–9.  https://doi.org/10.1111/j.1346-8138.1999.tb03444.x.CrossRefPubMedGoogle Scholar
  38. 38.
    Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83(12):1583–90.  https://doi.org/10.1016/j.bcp.2012.01.001.CrossRefPubMedGoogle Scholar
  39. 39.
    Reich K SJ, Day R, et al. Change in weight with apremilast, an oral phosphodiesterase 4 inhibitor: pooled analysis of the ESTEEM 1 and ESTEEM 2 trials. Poster. Presented at: the 73rd Annual Meeting of the American Academy of Dermatology; 2015 Mar 20–24; San Francisco, CA.Google Scholar
  40. 40.
    Dattola A, Del Duca E, Saraceno R, Gramiccia T, Bianchi L. Safety evaluation of apremilast for the treatment of psoriasis. Expert Opin Drug Saf. 2017;16(3):381–5.  https://doi.org/10.1080/14740338.2017.1288714.CrossRefPubMedGoogle Scholar
  41. 41.
    Chiricozzi A, Saraceno R, Novelli L, Fida M, Caso F, Scarpa R, et al. Small molecules and antibodies for the treatment of psoriasis: a patent review (2010-2015). Expert Opin Ther Patents. 2016;26(7):757–66.  https://doi.org/10.1080/13543776.2016.1192129.CrossRefGoogle Scholar
  42. 42.
    Xeljanz [package insert].New York, NY: Pfizer Laboratories; 2015.Google Scholar
  43. 43.
    Fleischmann R, Kremer J, Cush J, Schulze-Koops H, Connell CA, Bradley JD, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495–507.  https://doi.org/10.1056/NEJMoa1109071.CrossRefPubMedGoogle Scholar
  44. 44.
    van Vollenhoven RF, Fleischmann R, Cohen S, Lee EB, Garcia Meijide JA, Wagner S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508–19.  https://doi.org/10.1056/NEJMoa1112072.CrossRefPubMedGoogle Scholar
  45. 45.
    Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167(3):668–77.  https://doi.org/10.1111/j.1365-2133.2012.11168.x.CrossRefPubMedGoogle Scholar
  46. 46.
    • Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet (London, England). 2015;386:552–61. First phase III study showing a non inferiority assessment of a small molecule compared to a biologic in psoriasis. CrossRefGoogle Scholar
  47. 47.
    Valenzuela F, Bissonnette R, Bakos N, TsaiT-F, Harper MK, Ports WC, et al. Tofacitinib in patients with moderate to severe chronic plaque psoriasis: long-term efficacy and safety up to 54 months in an open-label extension study. In: Program and abstracts, 26th EADV Congress; 13–17 September 2017, Geneva, Switzerland.Google Scholar
  48. 48.
    Langley R CA, Foley P, et al. Safety of tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: integrated data analysis from the global clinical trials. In: Program and abstracts, 73rd Annual Meeting of the American Academy of Dermatology; March 20, 2015; San Francisco, CA.Google Scholar
  49. 49.
    US Food and Drug Administration. Arthritis Advisory Committee Meeting. NDA 203214: tofacitinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had inadequate response to one or more disease-modifying anti-rheumatic drugs. May 9, 2012.Google Scholar
  50. 50.
    Pfizer receives complete response letter from FDA for oral XELJANZ® (tofacitinib citrate) supplemental new drug application for moderate to severe chronic plaque psoriasis [press release]. New York, NY: Pfizer Inc. October 14, 2015.Google Scholar
  51. 51.
    Ports WC, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013;169(1):137–45.  https://doi.org/10.1111/bjd.12266.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Concert pharmaceuticals Inc. Deuterated derivatives of ruxolitinib WO2013188783A1. 2013.Google Scholar
  53. 53.
    Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol. 2012;67(4):658–64.  https://doi.org/10.1016/j.jaad.2011.12.018.CrossRefPubMedGoogle Scholar
  54. 54.
    Ortiz-Ibanez K, Alsina MM, Munoz-Santos C. Tofacitinib and other kinase inhibitors in the treatment of psoriasis. Actas dermo-sifiliograficas. 2013;104(4):304–10.  https://doi.org/10.1016/j.adengl.2013.03.002.CrossRefPubMedGoogle Scholar
  55. 55.
    Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016;174(6):1266–76.  https://doi.org/10.1111/bjd.14403.CrossRefPubMedGoogle Scholar
  56. 56.
    Hansen RB, Kavanaugh A. Novel treatments with small molecules in psoriatic arthritis. Curr Rheumatol Rep. 2014;16(9):443.  https://doi.org/10.1007/s11926-014-0443-6.CrossRefPubMedGoogle Scholar
  57. 57.
    Papp K, Pariser D, Catlin M, Wierz G, Ball G, Akinlade B, et al. A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2015;173(3):767–76.  https://doi.org/10.1111/bjd.13745.CrossRefPubMedGoogle Scholar
  58. 58.
    Can-Fite Biopharma Ltd. Pharmaceutical composition comprising a3 adenosine receptor agonist (ib-meca/cf-101) for treatment of psoriasis. WO2011027348A1. 2011.Google Scholar
  59. 59.
    Fishman P, Bar-Yehuda S, Liang BT, Jacobson KA. Pharmacological and therapeutic effects of A3 adenosine receptor agonists. Drug Discov Today. 2012;17(7-8):359–66.  https://doi.org/10.1016/j.drudis.2011.10.007.CrossRefPubMedGoogle Scholar
  60. 60.
    David M, Akerman L, Ziv M, Kadurina M, Gospodinov D, Pavlotsky F, et al. Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial. J Eur Acad Dermatol Venereol : JEADV. 2012;26(3):361–7.  https://doi.org/10.1111/j.1468-3083.2011.04078.x.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fernando Valenzuela
    • 1
    • 2
    • 3
    Email author
  • Javier Fernández
    • 1
  • Pablo Santa María
    • 1
  1. 1.Centro Internacional de Estudios Clínicos - Probity Medical ResearchSantiagoChile
  2. 2.Department of Dermatology, Faculty of MedicineUniversity of ChileSantiagoChile
  3. 3.Department of DermatologyClínica Las CondesSantiagoChile

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