Approach

The aim of treating psoriasis is to decrease the percentage of body surface involved (aiming for complete disease clearance) in as short a time as possible, and to maintain remission. Effectiveness of therapy is usually monitored by both a disease severity tool such as the Psoriasis Area and Severity Index (PASI) and a quality-of life index, usually the Dermatology Life Quality Index.[48] 

Mild psoriasis

Topical treatments are the mainstay of therapy.[52][53]

Choice of formulation depends on the area of cover (e.g., lotion for scalp; cream for moist weeping lesions; and ointment for dry, lichenified, or scaly lesions).

For patients with limited psoriasis involvement, start with topical corticosteroids and a topical vitamin D analog.[54][55][56] [ Cochrane Clinical Answers logo ] [Evidence A] Topical calcineurin inhibitors are second-line agents. Emollients may be considered by those averse to pharmacologic options.

Topical corticosteroids

  • A topical corticosteroid in combination with a vitamin D analog is more effective in treating disease than either treatment alone.[55][57]

  • Combination therapy may help to reduce potential adverse effects associated with extensive use of topical corticosteroids.

  • The potency of topical corticosteroid used is determined by the extent of disease and the responsiveness of the patient to medications. Low-potency treatments are appropriate for lesions on the face or intertriginous areas.[58]

  • The combination product halobetasol/tazarotene has been approved for the treatment of plaque psoriasis in adults in some countries.

Topical vitamin D analogs

  • Agents such as calcipotriene bind with vitamin D-selective receptors and inhibit the hyperproliferation and abnormal differentiation of keratinocytes characteristic of psoriatic lesions.[58]

  • Calcipotriene has a relatively slow onset of action and its maximal effect is after 6 to 8 weeks. A two-compound formulation with betamethasone dipropionate appears to be superior to other topicals in scalp psoriasis and psoriasis vulgaris.[59][60]

  • Topical vitamin D analogs can be used alone for chronic therapy when psoriasis is under good control or when treatment needs to be applied long-term to the face or intertriginous areas.

Topical calcineurin inhibitors

  • Tacrolimus or pimecrolimus are often used as second-line agents in the treatment of psoriasis, especially facial, flexural, and genital psoriasis; however, this use is off-label.[61][62]

Moderate to severe psoriasis

Treatment options for moderate to severe psoriasis include phototherapy, conventional systemic therapy (including methotrexate, cyclosporine, or acitretin), apremilast, fumaric acid esters, and biologic therapy.[63]

Treatment should be supervised by a dermatologist.[64]

Phototherapy

  • Phototherapy for moderate to severe psoriasis includes narrow-band UVB or PUVA.[65]

  • Phototherapy is an effective treatment for psoriasis with skin clearance rates of 50% to 75% with narrow-band UVB, and up to 85% with PUVA.[66]

  • Phototherapy requires the patient to attend the clinic or hospital several times a week for the duration of treatment.

  • Adverse effects of phototherapy include phototoxicity (during and after treatment), and burning if the dose is not adequately controlled. There is a small increased risk of skin cancer; the risk is higher in Fitzparick skin types I and II.

Conventional systemic therapy

  • Methotrexate

    • A folic acid antagonist that works as an antiproliferative and anti-inflammatory agent that is considered a first-line systemic drug.

    • Methotrexate may increase the incidence of liver fibrosis in people who are overweight or who have diabetes.[67]

    • Folic acid is usually co-prescribed with methotrexate to minimize adverse effects (such as gastrointestinal symptoms and deranged liver function tests).[68] 

    • Subcutaneous methotrexate may be used in people who fail to respond to oral therapy or have nausea with oral treatment.

  • Cyclosporine

    • Suppresses T cells and pro-inflammatory cytokines (such as interleukin 2), inhibits antigen-presenting capacity of Langerhans cells, and impedes mast cell function of degranulation and cytokine production.

    • Cyclosporine is an effective treatment for psoriasis but has significant adverse effects, such as nephrotoxicity and hypertension.[69] It is, therefore, generally reserved for very extensive psoriasis requiring rescue to bring disease severity under relative control. 

    • Long-term use (i.e., >12 months) is not recommended.

  • Acitretin

    • An oral retinoid chemically related to vitamin A that helps to regulate epithelial cell growth.

    • Moderately effective in many cases and often combined with other treatments.

    • Do not use oral retinoids in women of childbearing age, as they are teratogenic.

    • Monitor liver function and blood lipid concentration.

  • Apremilast

    • An oral phosphodiesterase-4 inhibitor that works by modulating cyclic adenosine monophosphate levels, which in turn down-regulates inflammatory cytokines including tumor necrosis factor (TNF)-alpha and interleukins 23 and 17.

    • Clinical trials have shown apremilast to have modest efficacy in patients with moderate to severe psoriasis.[70][71][72]

    • Common adverse events included nausea, diarrhea, nasopharyngitis, and upper respiratory tract infection.[70][71][72]

    • Apremilast should be used with caution in patients with a history of depression.

  • Fumaric acid esters

    • Fumaric acid esters have immunosuppressive and anti-inflammatory properties.

    • Licensed for moderate to severe psoriasis in European countries. In the UK, dimethyl fumarate is licensed for the treatment of moderate to severe plaque psoriasis in adults.

    • Not approved in the US for cutaneous psoriasis but may be prescribed off-label in the US and other countries.[73][74][75][76] 

Biologic therapy

Biologics have been transformative in the management of psoriasis, clearing widespread severe disease and improving psoriatic arthritis. They act at a cellular level and target particular steps in the immunologic processes key to psoriasis activity.

A "living" (regularly updated) Cochrane network meta-analysis has demonstrated that all biologics are effective in improving psoriasis (90% or 90% improvement in PASI compared with baseline).[77] At class level, the biologic treatments that target interleukin (IL)-17, IL-12/23, IL-23, and TNF-alpha were significantly more effective than the small molecules and conventional systemic agents.[77] 

The results from another network meta-analysis of randomized controlled trials suggest that brodalumab, guselkumab, ixekizumab, and risankizumab are associated with the highest PASI response rates for both short- and long-term therapy.[78] 

Rare adverse effects include drug-induced lupus (associated with TNF-alpha inhibitors) and Candida infections (with IL‐17 inhibitors, typically mucocutaneous).[79]

Tuberculosis screening (e.g., tuberculin skin test, interferon-gamma release assay, asking about exposure and travel history, and chest x-ray) is recommended prior to initiation of biologic therapy.[79][80] Screening prior to initiation also includes an HIV and hepatitis B/C test.[79][80] 

All biologics are given as subcutaneous injections (patients administer themselves) except infliximab, which is given as an intravenous infusion.

  • TNF-alpha inhibitors

    • Include adalimumab, etanercept, infliximab, certolizumab.[81][82][83][84][85][86][87]

    • If clinically needed, certolizumab may be used in pregnancy.

  • Interleukin-12/23 inhibitors

    • Ustekinumab: a human monoclonal antibody that inhibits interleukins 12 and 23.[88][89][90][91] 

    • Guselkumab: a monoclonal antibody that inhibits IL-23; believed to provide similar health benefits to ixekizumab and secukinumab.[92][93] 

    • Risankizumab: a human monoclonal antibody that targets IL-23; significantly improved symptoms of moderate to severe psoriasis in clinical trials.[94]

    • Tildrakizumab: an IL-23 antagonist approved for the treatment of moderate to severe plaque psoriasis; efficacious when compared with placebo and etanercept in two phase 3 trials.[95] 

  • Interleukin-17 inhibitors

    • Secukinumab: a human monoclonal antibody; efficacious in clearing psoriasis plaques.[96][97][98] 

    • Ixekizumab: a monoclonal antibody; clinical trial data indicate that ixekizumab is highly effective in the treatment of moderate to severe psoriasis for up to 60 weeks of treatment.[99] 

    • Brodalumab: a monoclonal antibody that targets the IL-17 receptor, blocking the signaling pathway of interleukins 17A, 17F, and 25. Appears to be well tolerated and efficacious over a 2-year period.[100][101][102]

Principles of biologic therapy management

When considering a biologic agent, factors to take into account include:[64]

  • The goal of therapy (e.g., Physician Global Assessment, PASI, or body surface area)

  • Disease phenotype and pattern of activity

  • Disease severity and impact

  • Individual factors including age, comorbidities, conception plans, and body mass index.

Biologic therapy in patients with comorbid conditions

In patients with multiple sclerosis, TNF-alpha inhibitors are not recommended, while IL-17 inhibitors and ustekinumab are recommended first-line.

In patients with hepatitis B infection or latent tuberculosis, ustekinumab and IL-17 inhibitors are recommended, while TNF-alpha inhibitors should be used with caution.[103]

Biosimilars

Biosimilars are available for some biologic agents. The International Psoriasis Council has published a consensus statement to guide prescribing of biosimilars (generic agents highly similar to the originator biologic agent that can be prescribed at reduced cost).[104] 

A 2021 systematic review in a small sample of psoriasis patients determined that switching between reference adalimumab and biosimilars has no impact on efficacy, safety, and immunogenicity.[105]  

Erythrodermic psoriasis

Patients with erythrodermic psoriasis may need admission to hospital for intense topical treatment, fluid replacement, and electrolyte monitoring. Rapid and aggressive control is essential.

Initial treatment is often with cyclosporine for around 3 weeks to manage the flare. Patients who are more stable can be started with a biologic agent (e.g., a TNF-alpha inhibitor, ustekinumab).

Guttate psoriasis

The recommended treatment approach for guttate psoriasis largely mirrors the strategies employed for plaque psoriasis. Important differences include investigating for an infectious trigger, which may include a throat swab for streptococcal infection and a screen for HIV.

First-line treatment is phototherapy; oral systemic therapies (e.g., cyclosporine, methotrexate, acitretin) are second- and third-line options.[65][68][69][106][107][108] Cyclosporine is often prescribed first if guttate psoriasis is widespread and has not responded to phototherapy.[64]

Phototherapy requires the patient to attend the clinic or hospital several times a week for the duration of treatment.

Adverse effects of phototherapy include phototoxicity (during and after treatment), and burning if the dose is not adequately controlled. There is a small increased risk of skin cancer; risk is higher in Fitzparick skin types I and II.

Pustular psoriasis

Pustular psoriasis may require hospital admission if widespread. Fluid replacement, electrolyte monitoring, and supportive care is required for patients with extensive disease.

Pustular psoriasis may be treated with intestine topical therapy, acitretin, or a combination of acitretin and phototherapy. Other systemic agents such as methotrexate and cyclosporine may be prescribed. Cases are managed on a case-by-case basis under the supervision of a dermatologist.

Managing patients with comorbidities

Comorbidities in patients with psoriasis contribute to poorer health outcomes and have a significant health economic burden. Guidelines encourage physicians to address comorbidities when managing psoriasis.[109][110] 

Screen people with moderate to severe psoriasis for comorbidities annually. The most common comorbidities associated with psoriasis are hyperlipidemia, hypertension, obesity, type 2 diabetes, and depression.[111][112] 

People with psoriasis are also more likely to have non-alcoholic fatty liver disease and liver fibrosis, which may impact treatment with methotrexate.[113]

Management of psoriasis during the COVID-19 pandemic

  • The International Psoriasis Council is recording data on psoriasis and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and will provide updates to the global dermatology community.[114] 

  • Data suggests that treatments for psoriasis, including biologics, do not alter the risk of acquiring COVID-19 or having worse outcomes. It is recommended that patients who are not infected continue their biologic or oral therapies in most cases.[115][116]

  • Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) have been associated with higher hospitalization rates.[117]

  • Infection with COVID-19 may cause a flare of psoriasis. Resumption of psoriasis treatments withheld during SARS-CoV-2 infection should be decided on a case-by-case basis.[115] 

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