Skip to main content
SpringerLink
Log in

Combination Therapy in Psoriasis

An Evidence-Based Review

  • Evidence-Based Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Background

Psoriasis is a chronic, systemic, inflammatory condition for which a variety of treatment modalities exist. Combinations of therapies are used often in clinical practice to enhance efficacy and reduce drug toxicities.

Purpose

The purpose of this review is to assess the literature on the efficacy and safety of combination therapy in the treatment of psoriasis.

Methods

MEDLINE was reviewed to identify English-language publications from 1966 to 2011 examining combination therapy in psoriasis. Fifty-three articles met inclusion criteria and were included in this review. Randomized controlled trials addressing various combinations of treatment modalities for psoriasis were included. Data from these clinical studies were summarized and the outcomes were discussed.

Results

Large-scale, randomized controlled trials investigating the use of various combination therapies in psoriasis are limited. The strongest data support the use of combinations of vitamin D derivatives and corticosteroids as topical combinations and, to a lesser extent, the combination of other topical agents. Phototherapy and topical vitamin D derivatives as well as phototherapy in combination with oral retinoids are well supported in the literature. Combinations of systemic medications, though often used clinically, have little data to support their efficacy or safety.

Limitations

Our data were limited by the small number of clinical trials examining the multiple available combinations that are used in clinical practice.

Conclusions

The use of combination treatments falls within the standard of care for psoriasis, even if these combinations have not been extensively studied in clinical trials.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zachariae C, Mork NJ, Reunala T, et al. The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy. Acta Derm Venereol. 2008;88(5):495–501.

    Article  PubMed  CAS  Google Scholar 

  2. Lebwohl MG, Breneman DL, Goffe BS, et al. Tazarotene 0.1% gel plus corticosteroid cream in the treatment of plaque psoriasis. J Am Acad Dermatol. 1998;39(4 Pt 1):590–6.

    Article  PubMed  CAS  Google Scholar 

  3. Gisondi P, Del GM, Cotena C, et al. Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial. Br J Dermatol. 2008;158(6):1345–9.

    Article  PubMed  CAS  Google Scholar 

  4. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–41.

    Article  PubMed  Google Scholar 

  5. Fenton C, Plosker GL. Calcipotriol/betamethasone dipropionate: a review of its use in the treatment of psoriasis vulgaris. Am J Clin Dermatol. 2004;5(6):463–78.

    Article  PubMed  Google Scholar 

  6. Afifi T, De GG, Huang C, Zhou Y. Topical therapies for psoriasis: evidence-based review. Can Fam Physician. 2005;51:519–25.

    PubMed  Google Scholar 

  7. Bruner CR, Feldman SR, Ventrapragada M, et al. A systematic review of adverse effects associated with topical treatments for psoriasis. Dermatol Online J. 2003;9(1):2.

    PubMed  Google Scholar 

  8. Ortonne JP, Kaufmann R, Lecha M, et al. Efficacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial. Dermatology. 2004;209(4):308–13.

    Article  PubMed  CAS  Google Scholar 

  9. Papp KA, Guenther L, Boyden B, et al. Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis. J Am Acad Dermatol. 2003;48(1):48–54.

    Article  PubMed  Google Scholar 

  10. Hudson CP, Kempers S, Menter A, et al. An open-label, multicenter study of the efficacy and safety of a weekday/weekend treatment regimen with calcitriol ointment 3 microg/g and clobetasol propionate spray 0.05% in the management of plaque psoriasis. Cutis. 2011;88(4):201–7.

    PubMed  Google Scholar 

  11. Menter A, Sofen H, Smith S, et al. An open-label, multicenter study of the efficacy and safety of an AM/PM treatment regimen with clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g in the management of plaque psoriasis. Cutis. 2011;88(1):46–51.

    PubMed  Google Scholar 

  12. Austad J, Bjerke JR, Gjertsen BT, et al. Clobetasol propionate followed by calcipotriol is superior to calcipotriol alone in topical treatment of psoriasis. J Eur Acad Dermatol Venereol. 1998;11(1):19–24.

    Article  PubMed  CAS  Google Scholar 

  13. Brodell RT, Bruce S, Hudson CP, et al. A multi-center, open-label study to evaluate the safety and efficacy of a sequential treatment regimen of clobetasol propionate 0.05% spray followed by calcitriol 3 mg/g ointment in the management of plaque psoriasis. J Drugs Dermatol. 2011;10(2):158–64.

    PubMed  Google Scholar 

  14. Ruzicka T, Lorenz B. Comparison of calcipotriol monotherapy and a combination of calcipotriol and betamethasone valerate after 2 weeks’ treatment with calcipotriol in the topical therapy of psoriasis vulgaris: a multicentre, double-blind, randomized study. Br J Dermatol. 1998;138(2):254–8.

    Article  PubMed  CAS  Google Scholar 

  15. Salmhofer W, Maier H, Soyer HP, et al. Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diflucortolone valerate in chronic plaque psoriasis. Acta Derm Venereol Suppl (Stockh). 2000;211:5–8.

    Article  Google Scholar 

  16. Katoh N, Kishimoto S. Combination of calcipotriol and clobetasol propionate as a premixed ointment for the treatment of psoriasis. Eur J Dermatol. 2003;13(4):382–4.

    PubMed  CAS  Google Scholar 

  17. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol. 2009;60(4):643–59.

    Article  PubMed  Google Scholar 

  18. Koo J, Cuffie CA, Tanner DJ, et al. Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study. Clin Ther. 1998;20(2):283–91.

    Article  PubMed  CAS  Google Scholar 

  19. Tiplica GS, Salavastru CM. Mometasone furoate 0.1% and salicylic acid 5% vs. mometasone furoate 0.1% as sequential local therapy in psoriasis vulgaris. J Eur Acad Dermatol Venereol. 2009;23(8):905–12.

    Article  PubMed  CAS  Google Scholar 

  20. Lebwohl M. Clinical efficacy and safety of tazarotene: optimizing clinical results. Cutis. 1998;61(2 Suppl):27–9.

    PubMed  CAS  Google Scholar 

  21. Guenther LC, Poulin YP, Pariser DM. A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. Clin Ther. 2000;22(10):1225–38.

    Article  PubMed  CAS  Google Scholar 

  22. Green L, Sadoff W. A clinical evaluation of tazarotene 0.1% gel, with and without a high- or mid-high-potency corticosteroid, in patients with stable plaque psoriasis. J Cutan Med Surg. 2002;6(2):95–102.

    Article  PubMed  Google Scholar 

  23. Menter A, Abramovits W, Colon LE, et al. Comparing clobetasol propionate 0.05% spray to calcipotriene 0.005% betamethasone dipropionate 0.064% ointment for the treatment of moderate to severe plaque psoriasis. J Drugs Dermatol. 2009;8(1):52–7.

    PubMed  Google Scholar 

  24. Monastirli A, Georgiou S, Pasmatzi E, et al. Calcipotriol plus short-contact dithranol: a novel topical combination therapy for chronic plaque psoriasis. Skin Pharmacol Appl Skin Physiol. 2002;15(4):246–51.

    Article  PubMed  CAS  Google Scholar 

  25. Levine D, Even-Chen Z, Lipets I, et al. Pilot, multicenter, double-blind, randomized placebo-controlled bilateral comparative study of a combination of calcipotriene and nicotinamide for the treatment of psoriasis. J Am Acad Dermatol. 2010;63(5):775–81.

    Article  PubMed  CAS  Google Scholar 

  26. Rim JH, Park JY, Choe YB, et al. The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy. Am J Clin Dermatol. 2003;4(7):507–10.

    Article  PubMed  Google Scholar 

  27. Van De Kerkhof PC, Cambazard F, Hutchinson PE, 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.

    Article  PubMed  Google Scholar 

  28. Gollnick HP. Oral retinoids: efficacy and toxicity in psoriasis. Br J Dermatol. 1996;135(Suppl. 49):6–17.

    Article  PubMed  CAS  Google Scholar 

  29. van der Rhee HJ, Tijssen JG, Herrmann WA, et al. Combined treatment of psoriasis with a new aromatic retinoid (Tigason) in low dosage orally and triamcinolone acetonide cream topically: a double-blind trial. Br J Dermatol. 1980;102(2):203–12.

    Article  PubMed  Google Scholar 

  30. Grossman RM, Thivolet J, Claudy A, et al. A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: results of a multicenter placebo-controlled study. J Am Acad Dermatol. 1994;31(1):68–74.

    Article  PubMed  CAS  Google Scholar 

  31. Feliciani C, Zampetti A, Forleo P, et al. Nail psoriasis: combined therapy with systemic cyclosporin and topical calcipotriol. J Cutan Med Surg. 2004;8(2):122–5.

    Article  PubMed  Google Scholar 

  32. Warren RB, Chalmers RJ, Griffiths CE, et al. Methotrexate for psoriasis in the era of biological therapy. Clin Exp Dermatol. 2008;33(5):551–4.

    Article  PubMed  CAS  Google Scholar 

  33. de Jong EM, Mork NJ, Seijger MM, et al. The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial. Br J Dermatol. 2003;148(2):318–25.

    Article  PubMed  Google Scholar 

  34. Gupta R, Gupta S. Methotrexate-betamethasone weekly oral pulse in psoriasis. J Dermatolog Treat. 2007;18(5):291–4.

    Article  PubMed  CAS  Google Scholar 

  35. Thaci D, Ortonne JP, Chimenti S, et al. A phase IIIb, multicentre, randomized, double-blind, vehicle-controlled study of the efficacy and safety of adalimumab with and without calcipotriol/betamethasone topical treatment in patients with moderate to severe psoriasis: the BELIEVE study. Br J Dermatol. 2010;163(2):402–11.

    Article  PubMed  CAS  Google Scholar 

  36. Bagel J. LCD plus NB-UVB reduces time to improvement of psoriasis vs. NB-UVB alone. J Drugs Dermatol. 2009;8(4):351–7.

    PubMed  Google Scholar 

  37. Roussaki-Schulze AV, Kouskoukis C, Klimi E, et al. Calcipotriol monotherapy versus calcipotriol plus UVA1 versus calcipotriol plus narrow-band UVB in the treatment of psoriasis. Drugs Exp Clin Res. 2005;31(5–6):169–74.

    PubMed  CAS  Google Scholar 

  38. Dover JS, McEvoy MT, Rosen CF, et al. Are topical corticosteroids useful in phototherapy for psoriasis? J Am Acad Dermatol. 1989;20(5 Pt 1):748–54.

    Article  PubMed  CAS  Google Scholar 

  39. Torras H, Aliaga A, Lopez-Estebaranz JL, et al. A combination therapy of calcipotriol cream and PUVA reduces the UVA dose and improves the response of psoriasis vulgaris. J Dermatolog Treat. 2004;15(2):98–103.

    Article  PubMed  CAS  Google Scholar 

  40. Ring J, Kowalzick L, Christophers E, et al. Calcitriol 3 microg g-1 ointment in combination with ultraviolet B phototherapy for the treatment of plaque psoriasis: results of a comparative study. Br J Dermatol. 2001;144(3):495–9.

    Article  PubMed  CAS  Google Scholar 

  41. Woo WK, McKenna KE. Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial. Br J Dermatol. 2003;149(1):146–50.

    Article  PubMed  CAS  Google Scholar 

  42. Messer G, Degitz K, Plewig G, et al. Pretreatment of psoriasis with the vitamin D3 derivative tacalcitol increases the responsiveness to 311-nm ultraviolet B: results of a controlled, right/left study. Br J Dermatol. 2001;144(3):628–9.

    Article  PubMed  CAS  Google Scholar 

  43. Ramsay CA, Schwartz BE, Lowson D, et al. Calcipotriol cream combined with twice weekly broad-band UVB phototherapy: a safe, effective and UVB-sparing antipsoriatric combination treatment. The Canadian Calcipotriol and UVB Study Group. Dermatology. 2000;200(1):17–24.

    Article  PubMed  CAS  Google Scholar 

  44. Morison WL, Parrish JA, Fitzpatrick TB. Controlled study of PUVA and adjunctive topical therapy in the management of psoriasis. Br J Dermatol. 1978;98(2):125–32.

    Article  PubMed  CAS  Google Scholar 

  45. Menkes A, Stern RS, Arndt KA. Psoriasis treatment with suberythemogenic ultraviolet B radiation and a coal tar extract. J Am Acad Dermatol. 1985;12(1 Pt 1):21–5.

    Article  PubMed  CAS  Google Scholar 

  46. Mahajan R, Kaur I, Kanwar AJ. Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque-type psoriasis: a randomized single-blinded placebo-controlled study. J Eur Acad Dermatol Venereol. 2010;24(5):595–600.

    Article  PubMed  CAS  Google Scholar 

  47. Lowe NJ, Prystowsky JH, Bourget T, et al. Acitretin plus UVB therapy for psoriasis: comparisons with placebo plus UVB and acitretin alone. J Am Acad Dermatol. 1991;24(4):591–4.

    Article  PubMed  CAS  Google Scholar 

  48. Lauharanta J, Juvakoski T, Lassus A. A clinical evaluation of the effects of an aromatic retinoid (Tigason), combination of retinoid and PUVA, and PUVA alone in severe psoriasis. Br J Dermatol. 1981;104(3):325–32.

    Article  PubMed  CAS  Google Scholar 

  49. Green C, Lakshmipathi T, Johnson BE, et al. A comparison of the efficacy and relapse rates of narrowband UVB (TL-01) monotherapy vs. etretinate (re-TL-01) vs. etretinate-PUVA (re-PUVA) in the treatment of psoriasis patients. Br J Dermatol. 1992;127(1):5–9.

    Article  PubMed  CAS  Google Scholar 

  50. Lebwohl M, Christophers E, Langley R, et al. An international, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch Dermatol. 2003;139(6):719–27.

    Article  PubMed  CAS  Google Scholar 

  51. Jacobe H, Winterfield L, Kim F, et al. The role of narrowband UV-B plus alefacept combination therapy in the treatment of psoriasis. Arch Dermatol. 2008;144(8):1067–8.

    Article  PubMed  Google Scholar 

  52. Mease PJ, Reich K. Alefacept with methotrexate for treatment of psoriatic arthritis: open-label extension of a randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2009;60(3):402–11.

    Article  PubMed  Google Scholar 

  53. Reitamo S, Spuls P, Sassolas B, et al. Efficacy of sirolimus (rapamycin) administered concomitantly with a subtherapeutic dose of cyclosporin in the treatment of severe psoriasis: a randomized controlled trial. Br J Dermatol. 2001;145(3):438–45.

    Article  PubMed  CAS  Google Scholar 

  54. Mittal R, Malhotra S, Pandhi P, et al. Efficacy and safety of combination acitretin and pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial. Arch Dermatol. 2009;145(4):387–93.

    Article  PubMed  CAS  Google Scholar 

  55. Alpsoy E, Ozcan E, Cetin L, et al. Is the efficacy of topical corticosteroid therapy for psoriasis vulgaris enhanced by concurrent moclobemide therapy? A double-blind, placebo-controlled study. J Am Acad Dermatol. 1998;38(2 Pt 1):197–200.

    Article  PubMed  CAS  Google Scholar 

  56. Kerscher M, Volkenandt M, Plewig G, et al. Combination phototherapy of psoriasis with calcipotriol and narrow-band UVB. Lancet. 1993;342(8876):923.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No sources of funding were received to prepare this article. Dr. Feldman has received research, speaking and/or consulting support from Galderma Laboratories L.P., GSK/Stiefel, Leo Pharma, Abbott, Amgen, Astellas, Janssen, Taro, National Biological Corporation, National Psoriasis Foundation, and Novartis; he is the founder and majority owner of http://www.DrScore.com, and the founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. The other authors have no conflicts of interest that are directly relevant to the content of this article.

Author information

Authors and Affiliations

  1. Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1071, USA

    Cheryl J. Gustafson, Casey Watkins, Emily Hix & Steven R. Feldman

  2. Center for Dermatology Research, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Steven R. Feldman

  3. Center for Dermatology Research, Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Steven R. Feldman

Authors
  1. Cheryl J. Gustafson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Casey Watkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily Hix
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven R. Feldman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven R. Feldman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gustafson, C.J., Watkins, C., Hix, E. et al. Combination Therapy in Psoriasis. Am J Clin Dermatol 14, 9–25 (2013). https://doi.org/10.1007/s40257-012-0003-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-012-0003-7

Keywords

Search

Navigation