Psoriasis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

The mainstay of therapy for psoriasis consists of the application of topical agents directly onto the lesions. Topical agents include corticosteroids, vitamin D analogues, tar, anthralin, tazarotene, calcineurin inhibitors, and aloe vera extracts. Systemic therapy may also be used, including immunosupressants to counteract the progression of the disease.

Medical Therapy

Therapies are administered according to disease severity as assessed by the Psoriasis Area and Severity Index (PASI, ranging from 0 to 72), which takes into account appearance and extension of the lesions. Interventions in medical therapy for psoriasis include:

• Topical therapy
• Phototherapy
• Systemic therapy (immunosuppressive agents and biological therapy)

Topical therapy

• Medicated creams and ointments applied directly to psoriatic lesions can help decrease inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques.
• Approved drugs that can be used as topical therapy for acute management of psoriasis include:
  • Corticosteroids
  • Vitamin D analogues (calcipotriol)
  • Tar
  • Dithranol (anthralin)
  • Tazarotene (a retinoid)
  • Calcineurin inhibitors (tacrolimus and primecrolimus are used specially for flexural or facial psoriasis)
  • Aloe vera extract 0.5% hydrophilic cream
  • Anti-IL-8 monoclonal antibody cream
  • Betamethasone 17-valerate 21-acetate plus tretinoin plus salicylic acid
  • Fish oil plus occlussion
  • Combination of nicotinamide and calcipotriene 

• Combined treatment with vitamin D/corticosteroid on either the body or the scalp generates significantly better outcomes than vitamin D alone.

• The disadvantages of topical agents are that they can often irritate normal skin, can be time consuming and awkward to apply, cannot be used for long periods, can stain clothing, and can have a strong odor. As a result, it is sometimes difficult for people to maintain the regular application of these medications.
• Abrupt withdrawal from the use of some topical agents, particularly corticosteroids, can cause an aggressive recurrence of the condition.
• Some topical agents are commonly used in conjunction with other therapies, especially phototherapy.

Phototherapy

• It has long been recognized that daily, short, non-burning exposure to sunlight can help clear or improve psoriasis.
• Niels Finsen was the first physician to investigate the therapeutic effects of sunlight scientifically and to use sunlight in clinical practice. This became known as phototherapy.

• The narrow band part of the UVB spectrum (311 to 312 nm) is most helpful for the management of psoriasis. Exposure to UVB several times per week over several weeks can facilitate remission from psoriasis.

• Ultraviolet light treatment is frequently combined with topical (coal tar, calcipotriol) or systemic treatment (retinoids).
• The Ingram regime involves UVB and the application of anthralin paste.
• The Goeckerman regime combines coal tar ointment with UVB.

Systemic therapy

The following drugs may be used in the treatment of psoriasis:

Type of agent	Mechanism of action	Name	Molecular target	Formulation	Administration route
Biologic	Anti-metabolite	Methotrexate	DHFR	NA	Oral or IV
	Anti-T cell	Cyclosporine	Cyclophilin	NA	Oral or IV
		Alefacept	CD2	Human LFA-3/IgG1 fusion protein	IM or IV
		Efalizumab	CD11a	Humanized IgG1 monoclonal antibody	SC
		Abatacept	CTLA-4	Human CTLA4–Ig-IgG1 fusion protein	SC or IV
	Anticytokine	Etanercept	TNF	Human TNF-R (p75)-lgG1 fusion protein	SC
		Infliximab	TNF	Mouse-human IgG1 chimeric monoclonal antibody	IV
		Adalimumab	TNF	Human IgG1 monoclonal antibody	SC
		Ustekinumab	IL-2, IL-23	Human IgG1 monoclonal antibody	SC
		Briakinumab (discontinued in USA in 2011)	IL-12, IL-23	Human IgG1 monoclonal antibody	SC
		Guselkumab	IL-23p19	Human IgG1 monoclonal antibody	SC
		Brodalumab	IL-17R	Human IgG2 monoclonal antibody	SC
		Ixekizumab	IL-17	Humanized IgG4 monoclonal antibody	SC
		Secukinumab	IL-17	Human IgG1 monoclonal antibody	SC or IV
		Fezakinumab	IL-22	Human IgG1 monoclonal antibody	SC or IV
Small molecule	PDE4 inhibitor	Apremilast	PDE4	NA	Oral
	JAK inhibitor	Tofacitinib	JAK1 and JAK3	NA	Oral
		Baricitinib	JAK1 and JAK2	NA	Oral
	PKC inhibitor	AEB071	PKC	NA	Oral
	A3AR agonist	CF101	A3AR	NA	Oral

Abbreviations:

DHFR: Dihydrofolate reductase

SC: Sub-cutaneous

IV: Intra-venous

IM: Intra-muscular

NA: Not Applicable

PDE4: Phosphodiesterase 4

JAK: Janus Kinase

PKC: Protein Kinase C

LFA: Lymphocyte function associated antigen

TNF: Tumor necrosis factor

Treatment of psoriasis according to severity

The American Academy of Dermatology has published guidelines for the treatment of psoriasis. The guidelines are as follows:

• 1 Mild-moderate psoriasis
  • 1.1 Adults
    • Preferred regimen (1): Topical betamethasone plus calcipotriene q 12 hours for 1 week
    • Preferred regimen (2): Topical clobetasol propionate plus tazarotene q 12 hours for 2-4 weeks
    • Alternative regimen (1): Topical clobetasol propionate plus calcipotriene ointment q 12 hours for 2-4 weeks
    • Alternative regimen (2):Topical clobetasol propionate plus calcitriol ointment topical 3 mcg per g q 12 hours for 2-4 weeks
    • Alternative regimen (3): Topical clobetasol propionate plus tar q 12 hours for 2-4 weeks
    • Alternative regimen (4): Localized phototherapy 500-900 mJ per cm2 2-3 times per week for 10 weeks
    • Alternative regimen (5): Topical pimecrolimus 0.1% cream q 12 hours for 8 weeks
    • Alternative regimen (6): Topical tacrolimus 0.1% ointment q 12 hours for 8 weeks
  • 1.2 Pediatrics
    • Preferred regimen (1): Topical clobetasol propionate emulsion formulation foam 0.05% q 24 hours for 2 weeks
    • Preferred regimen (2): Topical hydrocortisone ointment 1%q 24 hours for 3 weeks
    • Preferred regimen (3): Topical calcipotriene 50 μg/g q 24 hours for 8 weeks
    • Alternative regimen (1): Topical tacrolimus 0.1% q 48 hours for 6 months
    • Alternative regimen (2): Topical pimecrolimus 1% q 48 hours for 11 weeks
    • Alternative regimen (3): Topical dithranol cream 0.1%-2% q 24 hours for 2 months
    • Alternative regimen (4): Topical UVB phototherapy 50 mJ initial dose 2-3 sessions per week; increments of 10% at each session for 12 weeks
• 2 Severe psoriasis
  • 2.1 Adults
    • Preferred regimen (1): Topical UVB phototherapy plus systemic PO methotrexate for 2-4 weeks
    • Alternative regimen (1): Topical UVB phototherapy plus systemic PO cyclosporine for 2-4 weeks
    • Alternative regimen (2): Topical UVB phototherapy plus systemic PO tazarotene for 2-4 weeks
    • Alternative regimen (3): Topical UVB phototherapy plus PUVA therapy (PO 8-methoxypsoralen 0.4-0.6 mg per kg given 1.5 hours before exposure to UVA) for 2-4 weeks
    • Alternative regimen (4): Topical UVB phototherapy plus IM alefacept 15 mg per week for 12 weeks
    • Alternative regimen (5): Topical UVB phototherapy plus SC efalizumab 0.7 mg per kg first dose followed by 1.0 mg per kg per week for 3 months
    • Alternative regimen (6): Topical UVB phototherapy plus SC adalimumab 80 mg the first week, 40 mg the second wk, followed by 40 mg every other week
    • Alternative regimen (7): Topical UVB phototherapy plus SC etanercept 50 mg twice per week for 3 months
    • Alternative regimen (8): Topical UVB phototherapy plus IV infliximab 5 mg per kg dose infusion schedule at week 0, 2, and 6 and then every 6-8 weeks for 3 months
  • 2.2 Pediatrics
    • Preferred regimen (1): Systemic PO methotrexate 0.2 and 0.4 mg per kg per week for 2 to 16 months
    • Preferred regimen (2):  Topical dithranol 0.016%-0.0625% q 24 hours for 3 months

Treatment of psoriasis according to disease sub-type

Treatment of various sub-types of psoriasis includes the following:

• 1 Localized pustular psoriasis
  • 1.1 Adults
    • Preferred regimen (1): Topical clobetasol propionate plus topical bath psoralen plus UVA phototherapy (PUVA) for 3 weeks
    • Alternative regimen (2): Topical clobetasol propionate plus PO acitretin 25-40 mg q 24 hours for 3 weeks
  • 1.2 Pediatrics
    • Preferred regimen (1) Topical clobetasol propionate plus topical tazarotene q 12 hours for 2-4 weeks
• 2 Nail psoriasis
  • 2.1 Adults
    • Preferred regimen (1): Topical clobetasol propionate q 24 hours for 2-4 weeks
    • Preferred regimen (2): Topical calcipotriene ointment q 12 hours for 2-4 weeks
• 3 Erythrodermic psoriasis
  • 3.1 Adults
    • Preferred regimen (1): IV infliximab 5 mg per kg at week 0, week 2, week 6 and methotrexate 15 mg per week
    • Preferred regimen (2): IV cyclosporine 3.5-4 mg per kg per day and etretinate 0.5-0.6 mg per kg per day for 1 week
    • Preferred regimen (3): SC etanercept 50 mg twice per week for 3 months
    • Preferred regimen (4): SC adalimumab 80 mg the first week, 40 mg the second wk, followed by 40 mg every other week
    • Preferred regimen (5): SC ustekinumab 45 mg at 0 and 4 weeks, and then every 12 weeks thereafter
    • Alternative regimen (1): IV infliximab 5 mg per kg at week 0, week 2, week 6 followed by 5 mg/kg every 8 weeks thereafter and acitretin 0.3-0.6 mg per kg
  • 3.2 Pediatrics
    • Preferred regimen (1): Topical clobetasol propionate plus topical tazarotene q 12 hours for 2-4 weeks
    • Alternative regimen (1): Topical UVB 2-3 sessions per week for 12 weeks

Treatment of psoriasis in specific populations

Specific populations may require modified regimens for the treatment of psoriasis. The following are the considerations:

• • 1.1 Pregnancy (methotrexate, tazarotene and acitretin are contraindicated)
    • Preferred regimen (1): Topical betamethasone plus petroleum jelly q 24 hours till remission
    • Alternative regimen (1): Topical UVB 2-3 sessions per week for 12 weeks
    • Alternative regimen (2): IV infliximab 5 mg per kg at week 0 , week 2, week 6 followed by 5 mg/kg every 8 weeks thereafter (discontinue at 30 weeks of gestation; avoid live vaccine administration to infants born to treated women is suggested until the age of seven months)
  • 1.2 Chronic hepatitis B (methotrexate, acitretin and cyclosporine are contraindicated)
    • Preferred regimen (1): Topical UVB phototherapy 2-3 sessions per week plus topical tar for 12 weeks
  • 1.3 Chronic hepatitis C (methotrexate, acitretin and cyclosporine are contraindicated; PUVA is relatively contraindicated in chronic liver disease)
    • Preferred regimen (1): Topical UVB phototherapy 2-3 sessions per week plus topical tar for 12 weeks
    • Alternative regimen (1): Topical UVB phototherapy plus PUVA therapy (PO 8-methoxypsoralen 0.4-0.6 mg per kg given 1.5 hours before exposure to UVA) for 2-4 weeks

Note: All treatments of psoriasis may include mid-potency topical corticosteroids (if not using topical steroids already), emollients, wet dressings, and oatmeal baths

Treatment of psoriatic arthritis

The following drugs may be used in the treatment of psoriatic arthritis:

Drug	Mechanism	Comments
NSAIDs	Inhibits cyclooxygenase	First line agent for symptomatic treatment
Corticosteroids	Inhibits inflammatory cytokines
Sulfasalazine	Unknown mechanism	One-third of patients have gastrointestinal distress, dizziness, or hepatotoxicity
Methotrexate	Inhibits dihydrofolate reductase and lymphocyte proliferation	Hepatotoxicity common
Cyclosporine	Inhibitor of T lymphocytes	More often used for cutaneous psoriasis
Leflunomide	Inhibits pyrimidine synthesis via dihydrofolate dehydrogenase inhibition	Effective for symptoms of arthritis, cutaneous psoriasis, and for prevention of disability
Etanercept	TNF-alpha receptor analogue that inhibits TNF-alpha action	Administered as subcutaneous injection
Infliximab	Chimeric monoclonal antibody that attaches to membrane-bound and soluble TNF-alpha	Administered as intravenous infusion
Adalimumab	Human anti TNF-alpha	Administered as subcutaneous injection
Alefacept	Human LFA-3/IgG fusion protein, which attaches to CD2 receptor on T cells	Combination with methotrexate for effective than monotherapy
Efalizumab	Humanized monoclonal antibody directed against CD11a, which disrupts T cell costimulatory LFA-1/ICAM-1 interaction	Associated with progressive multifocal leukoencephalopathy (PML)
Abatacept	Recombinant human fusion protein; binds CD80/86 and inhibits CD28 receptor on T cells	May be used for psoriatic arthritis, but not commonly employed as a therapy