This publication was published more than 5 years ago. The state of knowledge may have changed.

Phototherapy and systemic treatment for moderate to severe psoriasis

A systematic review and assessment of the medical, health economic and ethical aspects

Reading time approx. 30 minutes Published: Publication type:

SBU Assessment

Presents a comprehensive, systematic assessment of available scientific evidence for effects on health, social welfare or disability. Full assessments include economic, social and ethical impact analyses. Assessment teams include professional practitioners and academics. Before publication the report is reviewed by external experts, and scientific conclusions approved by the SBU Board of Directors.

Contact SBU
Published: Report no: 278 Registration no: SBU 2017/89 ISBN: 978-91-88437-20-4 https://int.sbu.se/278e

Background

It is estimated that between 2 and 4% of the pop­ulation have psoriasis. Psoriasis primarily affects the skin, but can also be associated with metabolic syndrome and an increased risk of excess weight, dia­betes and cardiovascular disease. Joint problems (psoriatic arthritis) are a common complication. Psoriasis is a chronic condition, and people with psoriasis may need treatment over extended periods of their lives.

Objective

The purpose of this review is to evaluate effects of treatments for moderate to severe psoriasis, and to highlight health economic and ethical issues related to treatment.

Method

The report systematically reviews randomised controlled trials (RCT) which investigate the effects of phototherapies, photochemotherapies and systemic treatments on psoriatic symptoms and health related quality of life in people with moderate to severe psoriasis. In addition, we present cost analyses of photo­therapies, photochemotherapies and conven­tional, synthetic systemic, treatments, and discuss ethical issues related to the treatment of psoriasis.

Results

The review is based on 77 RCTs. One of the included studies investigated effects of phototherapy, 17 of conventional synthetic drugs and 47 of biological drugs.

The results show that biological drugs approved for psoriasis are effective and that a high proportion of those treated achieve a clinically important improve­ment. Health related quality of life also improves, but for some substances, the evidence of a clinically relevant effect is weaker. Two conventional synthetic drugs, methotrexate and apremilast, are effective, but fewer of those treated reach a clinically important improvement.

Few studies compared active treatments, but available comparisons between etanercept (the biological substance first approved for psoriasis) and adalimumab, ixekizumab, sekukinumab or ustekinumab show more persons improve after treatment with the latter substances. A comparison between sekukinumab and ustekinumab shows more persons improve with sekukinumab. Comparisons of effects on quality of life show more improvement with ixekizumab than etanercept, but are uncertain for other comparisons.

Due to a lack of studies of adequate design and qual­ity­ we were unable to evaluate the effects of photo­therapy, photochemotherapy and the synthetic drugs acitretin, cyclosporine and fumaric acids on psoriasis.

Health economic and ethical issues

Analyses show that the yearly cost of treating one person differs significantly between different phototherapies and different conventional, synthetic drugs. Due to non-disclosure agreements, which affect the real, and to us unknown, prices healthcare providers pay, we chose not to evaluate the costs of biological substances. These comparatively costly drugs are currently only subsidized for persons who do not improve adequately when treated with other drugs.

A person with moderate to severe psoriasis needs access to effective treatment. Left untreated the condition can cause suffering and contribute to a higher risk for other long-term health issues. The challenge for health care providers is to offer effective treatment to all persons with psoriasis, while limiting access to more expensive treatment options to those who do not adequately respond to lower cost therapies.

Knowledge gaps

Most of the included studies compared different treatments with placebo. For some treatments we were unable to find any head-to-head trials comparing active treatments. More head-to-head trials are needed to determine whether one treatment performs better than another. There is also a need for long-term studies with a controlled design, as they may mirror clinical praxis better.

Results describing health related quality of life, the outcome that best describes experiences of treatment from the patient’s perspective, were often less reliable than outcomes describing the effect on psoriasis. A greater focus on quality of life in efficacy studies in future could increase their clinical value.

In addition, there is a need of more studies of effects and risks regarding the treatment of children with moderate to severe psoriasis.

Full report in Swedish

The full report in Swedish Ljusbehandling och systemisk behandling av psoriasis

Project group

Experts

  • Agneta Gånemo (Associate Professor)
  • Marcus Schmitt-Egenolf (Professor)
  • Oliver Seifert (Associate Professor)
  • Kristofer Thorslund (PhD)

SBU

  • Anna Christensson (Project Manager)
  • Agneta Brolund (Information Specialist)
  • Christel Hellberg (Assistant Project Manager)
  • Emin Hoxha Ekström (Health Economist)
  • Martin Norman (Assistant Project Manager)
  • Charlotta Ryk (Assistant Project Manager)
  • Anneth Syversson (Project Administrator)

References

  1. SBU. Utvärdering av metoder i hälso- och sjukvården: en handbok. Stockholm: Statens beredning för medicinsk och social utvärdering (SBU). Available from: http://www.sbu.se/metodbok/.
  2. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 2013;133:377-85.
  3. Hagg D, Eriksson M, Sundstrom A, Schmitt-Egenolf M. The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men. PLoS One 2013;8:e63619.
  4. Christophers E. Psoriasis–epidemiology and clinical spectrum. Clin Exp Dermatol 2001;26:314-20.
  5. Vachatova S, Andrys C, Krejsek J, Salavec M, Ettler K, Rehacek V, et al. Metabolic Syndrome and Selective Inflammatory Markers in Psoriatic Patients. J Immunol Res 2016;2016:5380792.
  6. Noe MH, Shin DB, Wan MT, Gelfand JM. Objective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study. J Invest Dermatol 2018;138:228-30.
  7. World Health Organization. Global report on psoriasis. 2016; [cited 2018 May 29] Available from: World Health Organization http://www.who.int/iris/handle/10665/204417
  8. Läkemedelsverket. Behandling av psoriasis – ny rekommendation. Information från Läkemedelsverket 2011;22(4):11-24.
  9. Fredriksson T, Pettersson U. Severe psoriasis-- oral therapy with a new retinoid. Dermatologica 1978;157:238-44.
  10. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)-- a simple practical measure for routine clinical use. Clin Exp Dermatol 1994;19:210-6.
  11. Nast A, Gisondi P, Ormerod AD, Saiag P, Smith C, Spuls PI, et al. European Dermatology Forum. European S3-Gudielines on the systemic treatment of psorisas vulgaris. 2015;29:2277-94.
  12. Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol 2005;152:861-7.
  13. Svenska sällskapet för dermatologi och venereologi (SSDV). SSDV:s behandlingsrekommendationer för systemisk behandling av psoriasis (2017-09-22). 2017.
  14. Lomholt G. Prevalence of skin diseases in a population; A census study from the Faroe islands. Dan Med Bull 1964;11:1-7.
  15. Swanbeck G, Inerot A, Martinsson T, Enerback C, Enlund F, Samuelsson L, et al. Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands. Br J Dermatol 1997;137:939-42.
  16. Duvic M, Johnson TM, Rapini RP, Freese T, Brewton G, Rios A. Acquired immunodeficiency syndrome-associated psoriasis and Reiter’s syndrome. Arch Dermatol 1987;123:1622-32.
  17. Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol 1992;128:39-42.
  18. Abel EA, DiCicco LM, Orenberg EK, Fraki JE, Farber EM. Drugs in exacerbation of psoriasis. J Am Acad Dermatol 1986;15:1007-22.
  19. Naldi L, Peli L, Parazzini F. Association of early-stage psoriasis with smoking and male alcohol consumption: evidence from an Italian case-control study. Arch Dermatol 1999;135:1479-84.
  20. Poikolainen K, Reunala T, Karvonen J, Lauharanta J, Karkkainen P. Alcohol intake: a risk factor for psoriasis in young and middle aged men? Bmj 1990;300:780-3.
  21. Frankel HC, Han J, Li T, Qureshi AA. The association between physical activity and the risk of incident psoriasis. Arch Dermatol 2012;148:918-24.
  22. de Korte J, Sprangers MA, Mombers FM, Bos JD. Quality of life in patients with psoriasis: a systematic literature review. J Investig Dermatol Symp Proc 2004;9:140-7.
  23. Wong T, Hsu L, Liao W. Phototherapy in psoriasis: a review of mechanisms of action. J Cutan Med Surg 2013;17:6-12.
  24. Läkemedelsverket. Otezla (apremilast). Information från Läkemedelsverket 2017;28(4). ISSN 1101-7104. 2017.
  25. FASS. Produktresumé för Skilarence (dimetylfumarat); [citerad 2018-05-28]. Hämtad från: www.fass.se
  26. Raaby L, Zachariae C, Ostensen M, Heickendorff L, Thielsen P, Gronbaek H, et al. Methotrexate Use and Monitoring in Patients with Psoriasis: A Consensus Report Based on a Danish Expert Meeting. Acta Derm Venereol 2017;97:426-32.
  27. FASS. Produktresumé för Neotigason (acitretin); [citerad 2018-05-28]. Hämtad från: www.fass.se
  28. Socialstyrelsen. Tandvårdriktlinjer: läkemedelsorsakad gingival överväxt (omfattande hyperplasi). [Citerad 2018-05-28]. Tillgänglig från: https://www.socialstyrelsen.se/tandvardsriktlinjer/sokiriktlinjerna/lakemedelsorsakadgingivaloverv1.
  29. Folkehelseinstituttet och Statens legemiddelverk N. Dimetylfumarat (LAS-41008) til behandling av moderat til alvorlig plakkpsoriasis hos voksne pasienter som har behov for systemisk beahndling: Folkehelseinstituttet och Statens legemiddelverk, Norge; 2016.
  30. FASS. Produktresumé för Tecfidera (dimetylfumarat); [Citerad 2018-05-28]. Hämtad från: www.fass.se
  31. Läkemedelsverket. Biologiska läkemedel; [Citerad 2018-05-28]. Hämtad från: https://lakemedelsverket.se/malgrupp/Foretag/Lakemedel/Biologiska-lakemedel/.
  32. Rane A, Hammarlund-Udenaes M. Kliniskt farmakologiska principer: terapifrekommendationer. In: Läkemedelsboken.
  33. Roman M, Chiu MW. Spotlight on brodalumab in the treatment of moderate-to-severe plaque psoriasis: design, development, and potential place in therapy. Drug Des Devel Ther 2017;11:2065-75.
  34. Läkemedelsverket. Biosimilar. 2017; [Citerad 2018-05-28]. Hämtad från: https://lakemedelsverket.se/malgrupp/Foretag/Lakemedel/Biologiska-lakemedel/Biosimilar/.
  35. Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T. How good are clinical severity and outcome measures for psoriasis?: quantitative evaluation in a systematic review. J Invest Dermatol 2010;130:933-43.
  36. Wallace AB. Burns; some experiences in local care. Br J Plast Surg 1951;4:224-9.
  37. Aitken RC. Measurement of feelings using visual analogue scales. Proc R Soc Med 1969;62:989-93.
  38. Bronsard V, Paul C, Prey S, Puzenat E, Gourraud PA, Aractingi S, et al. What are the best outcome measures for assessing quality of life in plaque type psoriasis? A systematic review of the literature. J Eur Acad Dermatol Venereol 2010;24 Suppl 2:17-22.
  39. Shikiar R, Willian MK, Okun MM, Thompson CS, Revicki DA. The validity and responsiveness of three quality of life measures in the assessment of psoriasis patients: results of a phase II study. Health & Quality of Life Outcomes 2006;4:71.
  40. McHorney CA, Ware JE, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 1993;31:247-63.
  41. Sullivan M, Karlsson J, Ware JE. The Swedish SF-36 Health Survey-- I. Evaluation of data quality, scaling assumptions, reliability and construct validity across general populations in Sweden. Soc Sci Med 1995;41:1349-58.
  42. Burstrom K, Sun S, Gerdtham UG, Henriksson M, Johannesson M, Levin LA, et al. Swedish experience-based value sets for EQ-5D health states. Qual Life Res 2014;23:431-42.
  43. Socialstyrelsen. Nationella riktlinjer för vård vid psoriasis. Stöd för styrning och ledning. Remissversion. Artikelnummer: 2018-3-15 2018.
  44. Norlin JM, Calara PS, Persson U, Schmitt-Egenolf M. Real-world outcomes in 2646 psoriasis patients: one in five has PASI ≥10 and/or DLQI ≥10 under ongoing systemic therapy. J Dermatolog Treat 2017;28:500-4.
  45. Socialstyrelsen. Patientregistret; [Citerad 2018-05-28]. Hämtad från http://www.socialstyrelsen.se/register/halsodataregister/patientregistret
  46. Psoriasisförbundet. [Citerad 2018-05-28]. Hämtad från https://www.psoriasisforbundet.se/
  47. PsoReg - Register för systembehandling av psoriasis. Årsrapport för 2017; [Citerad 2018-05-28]. Hämtad från: http://www.psoreg.se/publikationer/.
  48. Socialstyrelsen. PsoReg (Register för systembehandling av psoriasis); [Citerad 2018-05-28]. Hämtad från: http://www.socialstyrelsen.se/register/registerservice/nationellakvalitetsregister/psoregregisterforsystembehandl.
  49. Geale K, Henriksson M, Schmitt-Egenolf M. Evaluating equality in psoriasis health- care: a cohort study of the impact of age on prescription of biologics. Br J Dermatol 2016;174:579-87.
  50. Hagg D, Sundstrom A, Eriksson M, Schmitt-Egenolf M. Severity of Psoriasis Differs Between Men and Women: A Study of the Clinical Outcome Measure Psoriasis Area and Severity Index (PASI) in 5438 Swedish Register Patients. Am J Clin Dermatol 2017;18:583-90.
  51. Calara PS, Althin R, Carlsson KS, Schmitt-Egenolf M. Regional Differences in the Prescription of Biologics for Psoriasis in Sweden: A Register-Based Study of 4168 Patients. BioDrugs 2017;31:75-82.
  52. Yones SS, Palmer RA, Garibaldinos TT, Hawk JL. Randomized double-blind trial of the treatment of chronic plaque psoriasis: efficacy of psoralen-UV-A therapy vs narrowband UV-B therapy. Archives of Dermatology 2006;142:836-42.
  53. Gisondi P, Del Giglio M, Cotena C, Girolomoni G. Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, tcontrolled, investigator-blinded pilot trial. Br J Dermatol 2008;158:1345-9.
  54. Caproni M, Antiga E, Melani L, Volpi W, Del Bianco E, Fabbri P. Serum levels of IL-17 and IL-22 are reduced by etanercept, but not by acitretin, in patients with psoriasis: a randomized-controlled trial. J Clin Immunol 2009;29:210-4.
  55. Lee JH, Youn JI, Kim TY, Choi JH, Park CJ, Choe YB, et al. A multicenter, randomized, open-label pilot trial assessing the efficacy and safety of etanercept 50 mg twice weekly followed by etanercept 25 mg twice weekly, the combination of etanercept 25 mg twice weekly and acitretin, and acitretin alone in patients with moderate to severe psoriasis. BMC Dermatology 2016;16:11.
  56. 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;173:1387-99.
  57. Reich K, Gooderham M, Green L, Bewley A, Zhang Z, Khanskaya I, et al. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE). J Eur Acad Dermatol Venereol 2017;31:507-517.
  58. Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet 2012;380:738-46.
  59. 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.
  60. Strober B, Bagel J, Lebwohl M, Stein Gold L, Jackson JM, Chen R, et al. Efficacy and Safety of Apremilast in Patients With Moderate Plaque Psoriasis With Lower BSA: Week 16 Results from the UNVEIL Study. J Dermatolog: JDD 2017;16:801-8.
  61. Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. J Dermatolog 2017;44:873-84.
  62. Thaci D, Kimball A, Foley P, Poulin Y, Levi E, Chen R, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: Results of two phase III randomized, controlled trials. J Eur Acad Dermatol Venereol 2016;18:18.
  63. Crowley J, Thaci D, Joly P, Peris K, Papp KA, Goncalves J, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for >=156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol 2017;77:310-317.e1.
  64. Meddelande till hälso- och sjukvårdspersonal. Otezla (apremilast): Nya viktiga råd angående självmordsstankar och självmordsbeteende; [citerad 2018-05-28]. Hämtad från: https://lakemedelsverket.se/upload/halso-och-sjukvard/forskrivning/DHPC/Otezla-DHPC-2016-11-07.pdf.
  65. Flytstrom I, Stenberg B, Svensson A, Bergbrant IM. Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial. Br J Dermatol 2008;158:116-21.
  66. 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 Eng J Med 2003;349:658-65.
  67. Weinstein GD, Frost P. Methotrexate for psoriasis. A new therapeutic schedule. Arch Dermatol 1971;103:33-8.
  68. Mrowietz U, Szepietowski JC, Loewe R, Van de Kerkhof P, Lamarca R, Ocker WG, et al. Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: A randomised, double-blind, Fumaderm and placebo-controlled trial (BRIDGE). Br J Dermatol 2016;12:12
  69. Fallah Arani S, Neumann H, Hop WC, Thio HB. Fumarates vs. methotrexate in moderate to severe chronic plaque psoriasis: a multicentre prospective randomized controlled clinical trial. Br J Dermatol 2011;164:855-61.
  70. Pathirana D, Ormerod AD, Saiag P, Smith C, Spuls PI, Nast A, et al. European S3-guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009;23 Suppl 2:1-70.
  71. Ho SG, Yeung CK, Chan HH. Methotrexate versus traditional Chinese medicine in psoriasis: a randomized, placebo-controlled trial to determine efficacy, safety and quality of life. Clinical & Experimental Dermatology 2010;35:717-22.
  72. Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, et al. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol 2008;158:558-66.
  73. 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.
  74. van Roon EN, van de Laar MAFJ. Methotrexate bioavailability. Clin Exp Rheumatol 2010;28:S27-S32.
  75. Asahina A, Nakagawa H, Etoh T, Ohtsuki M, Author A, Department of Dermatology S, et al. Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study. J Dermatol 2010;37:299-310.
  76. Cai L, Gu J, Zheng J, Zheng M, Wang G, Xi LY, et al. Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study. J Eur Acad Dermatol Venereol 2016;9:9.
  77. Gordon KB, Langley RG, Leonardi C, Toth D, Menter MA, Kang S, et al. 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.
  78. Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, et al. Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial. J Am Acad Dermatol 2008;58:106-15.
  79. Revicki DA, Willian MK, Menter A, Gordon KB, Kimball AB, Leonardi CL, et al. Impact of adalimumab treatment on patient-reported outcomes: results from a Phase III clinical trial in patients with moderate to severe plaque psoriasis. J Dermatol Treat 2007;18:341-50.
  80. Shikiar R, Heffernan M, Langley RG, Willian MK, Okun MM, Revicki DA. Adalimumab treatment is associated with improvement in health-related quality of life in psoriasis: patient-reported outcomes from a phase II randomized controlled trial. J Dermatol Treat 2007;18:25-31.
  81. Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, et al. A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis. N Engl J Med 2015;373:136-44.
  82. Blauvelt A, Papp K, Griffiths C, Randazzo B, Wasfi Y, Shen Y, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol 2017;76:405-17.
  83. Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol 2017;76:418-31.
  84. Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol 2012;66:241-51.
  85. Papp K, Thaci D, Marcoux D, Weibel L, Philipp S, Ghislain PD, et al. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet 2017;390:40-9.
  86. van de Kerkhof PC, Segaert S, Lahfa M, Luger TA, Karolyi Z, Kaszuba A, et al. Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension. Br J Dermatol 2008;159:1177-85.
  87. Papp KA, Tyring S, Lahfa M, Prinz J, Griffiths CE, Nakanishi AM, et al. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol 2005;152:1304-12.
  88. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet 2015;386:541-51.
  89. Krueger GG, Langley RG, Finlay AY, Griffiths CE, Woolley JM, Lalla D, et al. Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial. Br J Dermatol 2005;153:1192-9.
  90. Langley RG, Paller AS, Hebert AA, Creamer K, Weng HH, Jahreis A, et al. Patient-reported outcomes in pediatric patients with psoriasis undergoing etanercept treatment: 12-week results from a phase III randomized controlled trial. J Am Acad Dermatol 2011;64:64-70.
  91. Paller AS, Siegfried EC, Langley RG, Gottlieb AB, Pariser D, Landells I, et al. Etanercept treatment for children and adolescents with plaque psoriasis. N Engl J Med 2008;358:241-51.
  92. Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006;367:29-35.
  93. Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, et al. A randomized trial of etanercept as monotherapy for psoriasis. Archives of Dermatology 2003;139:1627-32; discussion 1632.
  94. Leonardi CL, Powers JL, Matheson RT, Goffe BS, Zitnik R, Wang A, et al. Etanercept as monotherapy in patients with psoriasis. New Engl J Med 2003;349:2014-22.
  95. Gottlieb AB, Leonardi C, Kerdel F, Mehlis S, Olds M, Williams DA, et al. Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 2011;165:652-60.
  96. Strober BE, Crowley JJ, Yamauchi PS, Olds M, Williams DA, Author A, et al. Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 2011;165:661-8.
  97. Bachelez H, 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.
  98. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis-- results of two phase 3 trials. N Engl J Med 2014;371:326-38.
  99. Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials.[Erratum appears in Lancet. 2017 Jul 15;390(10091):230; PMID: 28721878]. Lancet 2017;390:276-88.
  100. Tyring S, Gordon KB, Poulin Y, Langley RG, Gottlieb AB, Dunn M, et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol 2007;143:719-26.
  101. Leonardi C, Strober B, Gottlieb AB, Elewski BE, Ortonne JP, van de Kerkhof P, et al. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study. J Dermatol: JDD 2010;9:928-37.
  102. Paller AS, Siegfried EC, Pariser DM, Rice KC, Trivedi M, Iles J, et al. Long-term safety and efficacy of etanercept in children and adolescents with plaque psoriasis. J Am Acad Dermatol 2016;74:280-7.e1-3.
  103. Feldman SR, Gordon KB, Bala M, Evans R, Li S, Dooley LT, et al. 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;152:954-60.
  104. Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, et al. Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2004;51:534-42.
  105. Reich K, Nestle FO, Papp K, Ortonne JP, Evans R, Guzzo C, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet 2005;366:1367-74.
  106. Menter A, Feldman SR, Weinstein GD, Papp K, Evans R, Guzzo C, et al. A randomized comparison of continuous vs. intermittent infliximab maintenance regimens over 1 year in the treatment of moderate-to-severe plaque psoriasis. J Am Acad Dermatol 2007;56:31.e1-15.
  107. Yang HZ, Wang K, Jin HZ, Gao TW, Xiao SX, Xu JH, et al. Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial. Chinese Medical Journal 2012;125:1845-51.
  108. de Vries AC, Thio HB, de Kort WJ, Opmeer BC, van der Stok HM, de Jong EM, et al. A prospective randomised controlled trial comparing infliximab and etanercept in patients with moderate to severe chronic plaque type psoriasis Psoriasis Infliximab versus Etanercept Comparison Evaluation, the PIECE study. Br J Dermatol 2016;15:15.
  109. Gordon KB, Kimball AB, Chau D, Viswanathan HN, Li J, Revicki DA, et al. Impact of brodalumab treatment on psoriasis symptoms and health-related quality of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom Inventory. Br J Dermatol 2014;170:705-15.
  110. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med 2015;373:1318-28.
  111. Nakagawa H, Niiro H, Ootaki K. Brodalumab, a human anti-interleukin-17-receptor antibody in the treatment of Japanese patients with moderate-to-severe plaque psoriasis: Efficacy and safety results from a phase II randomized controlled study. J Dermatol Sci 2016;81:44-52.
  112. Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 2012;366:1181-9.
  113. Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016;175:273-86.
  114. Gottlieb A, Langley R, Philipp S, Martin R, Papavassilis C, Mpfofu S. Improvement in psoriasis symptoms and physical functioning with secukinumab compared with placebo and etanercept in subjects with moderate-to-severe plaque psoriasis and psoriatic arthritis: Results of a subanalysis from the phase 3 fixture study. Arthritis and rheumatism 2013;65:3322.
  115. Umezawa Y, Nakagawa H, Niiro H, Ootaki K, Japanese Brodalumab Study G. Long-term clinical safety and efficacy of brodalumab in the treatment of Japanese patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol 2016;29:29.
  116. Papp K, Leonardi C, Menter A, Thompson EH, Milmont CE, Kricorian G, et al. Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. J Am Acad Dermatol 2014;71:1183-1190.e3.
  117. FASS. Produktresumé för Kyntheum (brodalumab); [Citerad 2018-05-28]. Hämtad från: https://www.fass.se
  118. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med 2016;375:345-56.
  119. Blauvelt A, Gooderham M, Iversen L, Ball S, Zhang L, Agada NO, et al. Efficacy and safety of ixekizumab for the treatment of moderate-to-severe plaque psoriasis: Results through 108 weeks of a randomized, controlled phase 3 clinical trial (UNCOVER-3). J Am Acad Dermatol 2017;77:855-62.
  120. Reich K, Pinter A, Lacour JP, Ferrandiz C, Micali G, French LE, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol 2017;177:1014-23.
  121. Blauvelt A, Prinz JC, Gottlieb AB, Kingo K, Sofen H, Ruer-Mulard M, et al. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015;172:484-93.
  122. Paul C, Lacour JP, Tedremets L, Kreutzer K, Jazayeri S, Adams S, et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015;29:1082-90.
  123. Gottlieb AB, Blauvelt A, Prinz JC, Papanastasiou P, Pathan R, Nyirady J, et al. Secukinumab Self-Administration by Prefilled Syringe Maintains Reduction of Plaque Psoriasis Severity Over 52 Weeks: Results of the FEATURE Trial. J Dermatol: JDD 2016;15:1226-34.
  124. Lacour JP, Paul C, Jazayeri S, Papanastasiou P, Xu C, Nyirady J, et al. Secukinumab administration by autoinjector maintains reduction of plaque psoriasis severity over 52 weeks: results of the randomized controlled JUNCTURE trial. J Eur Acad Dermatol Venereol 2017;31:847-56.
  125. Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol 2016;20:20.
  126. Landells I, Marano C, Hsu MC, Li S, Zhu Y, Eichenfield LF, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: Results of the randomized phase 3 CADMUS study. J Am Acad Dermatol 2015;73:594-603.
  127. Lebwohl M, Papp K, Han C, Schenkel B, Yeilding N, Wang Y, et al. Ustekinumab improves health-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial. Br J Dermatol 2010;162:137-46.
  128. Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1).[Erratum appears in Lancet. 2008 May 31;371(9627):1838]. Lancet 2008;371:1665-74.
  129. Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 2008;371:1675-84.
  130. Tsai TF, Ho JC, Song M, Szapary P, Guzzo C, Shen YK, et al. Efficacy and safety of ustekinumab for the treatment of moderate-to-severe psoriasis: a phase III, randomized, placebo-controlled trial in Taiwanese and Korean patients (PEARL). J Dermatol Sci 2011;63:154-63.
  131. Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol 2013;168:844-54.
  132. Kimball AB, Papp KA, Wasfi Y, Chan D, Bissonnette R, Sofen H, et al. Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years in the PHOENIX 1 study. J Eur Acad Dermatol Venereol 2013;27:1535-45.
  133. Griffiths CEM, Strober BE, Van PK, Ho V, Fidelus-Gort R, Yeilding N, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Eng J Med 2010;362:118-128.
  134. Langan SM, Heerey A, Barry M, Barnes L. Cost analysis of narrowband UVB phototherapy in psoriasis. J Am Acad Dermatol 2004;50:623-6.
  135. Psoriasisförbundet. Behandling av psoriasis; [Citerad 2018-05-28]. Hämtad från: https://www.psoriasisforbundet.se/fakta-o-rad/om-psoriasis/behandling-av-psoriasis/ 2018.
  136. Opmeer BC, Heydendael VM, De Borgie CA, Spuls PI, Bossuyt PM, Bos JD, et al. Costs of treatment in patients with moderate to severe plaque psoriasis: economic analysis in a randomized controlled comparison of methotrexate and cyclosporine. Archives of Dermatology 2004;140:685-90.
  137. Socialstyrelsen. Statistikdatabas för diagnoser i öppen vård; [Citerad 2018-05-28]. Hämtad från: http://www.socialstyrelsen.se/statistik/statistikdatabas/diagnoserispecialiseradoppenvard 2017.
  138. Norrlandstingens regionförbund. Regional Prislista 2017 för Norra sjuk- vårdsregionen, länssjukvård och primärvård; [Citerad 2018-05-28]. Hämtad från: http://www.norrlandstingen.se/halso-och-sjukvard/avtal-och-priser/prislistor-norra-sjukvardsregionen/
  139. Samverkansnämnden sydöstra sjukvårdsregionen. Priser och ersättningar för sydöstra sjukvårdsregionen 2017; [Citerad 2018-05-28]. Hämtad från https://plus.rjl.se/infopage.jsf?nodeId=41089
  140. Södra regionvårdsnämnden. Regionala priser och ersättningar för södra sjukvårdsregionen 2017; [Citerad 2018-05-28]. Hämtad från: http://sodrasjukvardsregionen.se/avtal-priser/regionala-priser-och-ersattningar-foregaende-ar/
  141. Västra sjukvårdsregionen. Utomlänspriser 2017. För vårdtjänster enligt samverkansavtal om hälso- och sjukvård inom Västra sjukvårdsregionen; [citerad 2018-05-28]. Hämtad från https://alfresco.vgregion.se/alfresco/service/vgr/storage/node/content/workspace/SpacesStore/56e76d52-2328-42b0-822d-a52919d0791a/Utoml%C3%A4nsprislista%202017-1.pdf?a=false&guest=true
  142. Samverkansnämnden Uppsala-Örebro sjukvårdsregion. Regional prislista 2017; [Citerad 2018-05-28]. Hämtad från: http://svnuppsalaorebro.se/3-styrande/prislistor/2017/kommentarer_regionala_prislistan_2017.pdf
  143. Tandvårds- och läkemedelsförmånsverket (TLV). Databas för läkemedel och beslut; [citerad 2018-05-28]. Hämtad från: https://www.tlv.se/beslut/sok-i-databasen.html.
  144. Psoriasisföreningen i Stockholms län. ”Nya riktlinjer för provtagning vid systembehandling” Psoriasisföreningen i Stockholms län. 2011.
  145. Tandvårds- och läkemedelsförmånsverket (TLV). Tandvårds- och läkemedelsförmånsverkets allmänna råd TLVAR 2017:1
  146. SCB. Inkomst av tjänst: [Citerad 2018-05-28]. Hämtad från: http://www.statistikdatabasen.scb.se/pxweb/sv/ssd/START__HE__HE0110__HE0110A/InkAvTjanst/?rxid=f3cf8b74-5b21-4288-bf2a-46599a21725b. 2017;2017.
  147. ekonomifakta.se. Sociala avgifter; [Citerad 2018-05-28]. Hämtad från: http://www.ekonomifakta.se/sv/Fakta/Arbetsmarknad/Arbetsgivaravgift/Sociala-avgifter. 2017.
  148. National Institute for Health and Care Excellence (NICE). Psorisasis: assessment and management: National Institute for Health and Care Excellence (NICE). Clinical gudieline [CG153]. 2012, last updated 2017.
  149. FASS. Produktresumé för Stelara (ustekinumab); [citerad 2018-05-28]. Hämtad från: www.fass.se
  150. Larsson PA, Liden S. Prevalence of skin diseases among adolescents 12-- 16 years of age. Acta Derm Venereol 1980;60:415-23.
  151. Matusiewicz D, Koerber A, Schadendorf D, Wasem J, Neumann A. Childhood psoriasis-- an analysis of German health insurance data. Pediatr Dermatol 2014;31:8-13.
  152. Rose K, Happle R. The Effect of Regulation on Pediatric Psoriasis Drug Approvals: The Challenge of the European Union Pediatric Investigation Plans. Pediatr Dermatol 2017;34:e154-e159.
  153. Fortina AB, Bardazzi F, Berti S, Carnevale C, Di Lernia V, El Hachem M, et al. Treatment of severe psoriasis in children: recommendations of an Italian expert group. Eur J Pediatr 2017;176:1339-54.
  154. Osmancevic A, Ståhle M. Behandling av psoriasis: från tjära till biologiska läkemedel. Läkartidningen 2017;114:1-6.
  155. Chen X, Yang M, Cheng Y, Liu GJ, Zhang M. Narrow-band ultraviolet B phototherapy versus broad-band ultraviolet B or psoralen-ultraviolet A photochemotherapy for psoriasis. Cochrane Database Syst Rev 2013:Cd009481.
Page published
To top