Psoriasis Guidelines

Guidelines on the management and treatment of psoriasis with topical and alternative therapies, nonbiologic therapies, phototherapy, and biologic therapies were published in February 2021 by the American Academy of Dermatology and the National Psoriasis Foundation in the Journal of the American Academy of Dermatology. ^[58]

Topical and alternative treatments

Topical therapies, tools to assess the severity of psoriasis, and alterative/complementary medicines are addressed, as follows:

• Topical corticosteroids - Recommended for plaque psoriasis in nonintertriginous areas
• Steroid-sparing agents (eg, vitamin D analogs, tazarotene, and calcineurin inhibitors, alone or in combination with steroids) - Confer lower risk of steroid-induced adverse effects; alternate use with steroids is key to long-term management
• Other topical agents (eg, salicylic acid, emollients, anthralin, coal tar) - Can be use alone or in combination with topical steroids
• Topicals combined with biologic or systemic therapies - Help increase overall efficacy of therapy
• Severity measurement tools - Physician’s Global Assessment and body surface area (clinical practice); Psoriasis Area Severity Index (clinical trials); Dermatology Life Quality Index, Psoriasis Symptom Inventory, and pruritus assessment (subjective symptoms and quality of life)
• Alternative medicines and complementary therapies (no recommendations, owing to lack of evidence) - Traditional Chinese medicine, herbal therapies (eg, aloe vera, St. John’s wort), diet/dietary supplements (eg, fish oil, vitamin D, turmeric/curcumin, zinc, gluten-free diet), body/mind interventions (eg, hypnosis, stress reduction, meditation)

Nonbiological therapies

Covered in the guideline are recommendations and efficacy and safety information on 12 oral systemic, nonbiologic medications, as follows:

• Methotrexate - Moderate-to-severe psoriasis in adults
• Apremilast - Moderate-to-severe psoriasis in adults
• Cyclosporine - Severe, recalcitrant psoriasis; in addition, erythrodermic, generalized pustular psoriasis and/or palmoplantar psoriasis
• Acitretin - Monotherapy or combination therapy with PUVA or UVB
• Other nonbiologics (not FDA-approved for psoriasis) - Tofacitinib, hydroxyurea, mycophenolate mofetil, azathioprine, leflunomide, tacrolimus, and thioguanine

Phototherapy

The following phototherapy options are discussed in the guideline, with regard to dosing regimen, efficacy, and adverse effects:

• Narrowband UVB
• Broadband UVB
• Targeted UVB - Excimer laser, excimer light, targeted narrowband UVB light
• PUVA - Topical, oral, bath
• Photodynamic therapy
• Grenz ray
• Climatotherapy
• Visible light
• Goeckerman therapy (not a form of phototherapy)
• Pulsed dye laser

Biological medications

Treatment recommendations are offered on the following biologic agents, with FDA approval date in parentheses:

• TNF inhibitors - Etanercept (4/30/2004), infliximab (9/27/2006), adalimumab (1/22/2008), certolizumab (5/27/2018)
• IL-12/IL-23 inhibitor - Ustekinumab (9/25/2009)
• IL-17 inhibitors - Secukinumab (1/21/2015), ixekizumab (3/22/2016), brodalumab (2/15/2017)
• IL-23 inhibitors - Guselkumab (7/13/2017), tildrakizumab (3/21/2018), risankizumab (pending)

Guidelines on psoriasis biologic therapy from the British Association of Dermatologists  ^[59]

Clinical practice guidelines for biologic therapy for psoriasis were updated in October 2020 by the British Association of Dermatologists.

Use of biologic therapy

Biologic therapy for psoriasis should be initiated and supervised only by specialist physicians who are experienced in the diagnosis and treatment of psoriasis. The routine monitoring can be delegated to other healthcare professionals, such as clinical nurse specialists. Other relevant healthcare professionals should be consulted in cases that involve psoriatic arthritis or other multiple comorbidities.

Coordination of care providers, along with the patient, is necessary with regard to arrangements for drug administration, monitoring, and follow‐up.

Ensure that people with psoriasis who are starting biologic therapy have an opportunity to participate in long‐term safety registries.

Criteria for use of biologic therapy

Criteria for offering biologic therapy are as follows:

• Psoriasis requiring systemic therapy
• Failure of, intolerance to, or contraindications for methotrexate and cyclosporine
• Psoriasis has significant impact on physical, psychological, or social functioning: Extensive (>10% body surface area or Psoriasis Area and Severity Index ≥10) and/or psoriasis is severe at localized sites and is associated with significant functional impairment

Criteria for considering biologic therapy are as follows:

• Psoriasis that fulfills disease severity criteria and is accompanied by active psoriatic arthritis
• Psoriasis that is persistent (eg, relapses rapidly) when off therapy that cannot be continued long term

Choice of biologic therapy

Considerations to take into account before initiating or making changes to biologic therapy are as follows:

• The presence of both psoriasis and psoriatic arthritis, in consultation with a rheumatologist
• Presence and phenotype of psoriatic arthritis, which may influence access to and choice and dose of biologic therapy

The following psoriasis-related factors should be considered when tailoring the choice of biologic agent to the needs of the patient:

• Therapeutic goals
• Disease phenotype and activity pattern
• Disease severity and impact
• Additional presence of psoriatic arthritis
• Outcomes of prior psoriasis treatments

Other individual factors to consider when tailoring the choice of biologic agent to the needs of the patient are as follows:

• Patient age
• Current or past comorbidities
• Pregnancy status and/or conception plans
• Patient body weight
• Patient opinion on drug administration route or dosing frequency
• Likelihood of compliance with treatment
• Drug cost: dministration expense, dosage, price per dose, commercial arrangements

In adults, offer any of the currently approved biologic therapies as first‐line therapy, substituting a different approved biologic should the first one fail. Tumor necrosis factor (TNF) antagonists or interleukin 17 antagonists should be offered as first-line therapy for patients with psoriatic arthritis. Etanercept can be considered in TNF antagonist–eligible patients if other biologics have failed or cannot be used, or if a short half‐life is important. Infliximab should be reserved for very severe disease or if age-based dosing is important, or if other biologics have failed or cannot be used.

For pediatric patients, adalimumab can be offered for patients aged 4 years or older, etanercept for patients aged 6 years or older, or ustekinumab for those aged 12 years or older, if they meet the criteria for biologic therapy. If these agents do not provide an adequate response, a specialist in pediatric biologic therapy should be consulted, along with consideration of the following:

• Advice about factors that may be contributing to the poor response, such as obesity and poor compliance
• Optimization of adjunctive therapy, such as switching from oral to subcutaneous methotrexate
• Supplementary or alternative nonbiologic therapies, such as inpatient topical therapy or systemic therapies

Important contraindications to biologic therapies

Contraindications for the use of biologic therapies in psoriasis patients are as follows:

• TNF antagonist use with demyelinating diseases (and possible use of alternative therapies in those with first‐degree relatives with demyelinating disease)
• TNF antagonist use with severe cardiac failure (New York Heart Association class III and IV)
• Inflammatory bowel disease, which warrants gastroenterology specialist consultation before offering brodalumab, ixekizumab, or secukinumab
• Relative contraindication in people undergoing elective surgery

Guidelines on the management and treatment of psoriasis with biologics by the American Academy of Dermatology and the National Psoriasis Foundation  ^[60]

TNF-alpha Inhibitors

Etanercept recommendations are as follows:

• Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended starting dose of 50 mg; self-administered SC injection twice weekly for 12 consecutive weeks
• Recommended maintenance dose of 50 mg once weekly; 50 mg twice weekly is more efficacious than once weekly and may be required for better disease control in some patients
• Recommended as monotherapy option in adults with moderate-to-severe plaque psoriasis affecting the scalp or nails
• Can be recommended as monotherapy option for adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe plaque psoriasis
• Recommended monotherapy option in adults with plaque psoriasis of any severity when associated with significant psoriatic arthritis
• Recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis
• Recommended combination treatment option with methotrexate for moderate-to-severe plaque psoriasis in adults
• May be combined with acitretin, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Infliximab recommendations are as follows:

• Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended starting dose is an infusion of 5 mg/kg administered at week 0, week 2, and week 6; thereafter, administered every 8 weeks
• Recommended to be administered at more frequent intervals (less than q8wk and as frequently as q4wk during maintenance phase) and/or at a higher dose (up to 10 mg/kg) for better disease control in some adults
• Recommended as monotherapy option for moderate-to-severe plaque psoriasis affecting the palms and soles (plaque-type palmoplantar psoriasis), nails, or scalp in adults
• Can be recommended as monotherapy option in adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe plaque psoriasis
• Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with significant psoriatic arthritis; it also inhibits radiographically detected joint damage in psoriatic arthritis
• Recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis
• May be combined with acitretin, methotrexate, or apremilast for moderate-to-severe plaque psoriasis in adults

Adalimumab recommendations are as follows:

• Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended starting dose of 80 mg taken as two self-administered SC 40-mg injections, followed by a 40-mg self-administered SC injection 1 week later, followed by 40-mg self-administered SC injections every 2 weeks thereafter
• Maintenance dose of 40 mg/wk recommended for better disease control in some patients
• Recommended as monotherapy option for adults with moderate-to-severe plaque psoriasis affecting the palms and soles (palmoplantar psoriasis), nails, or scalp
• Can be recommended as monotherapy option for adults patients with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe psoriasis
• Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with psoriatic arthritis
• Can be recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis
• May be combined with acitretin, methotrexate, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Certolizumab has been approved by the FDA for the treatment of plaque psoriasis, psoriatic arthritis, Crohn disease, ankylosing spondylitis, and rheumatoid arthritis. Approved dosing for moderate-to-severe psoriasis is 400 mg (two 200-mg SC injections) every other week. It is likely to possess class characteristics similar to those of other TNF-alpha inhibitors.

Interleukin-12/23 Inhibitors

Ustekinumab recommendations are as follows:

• Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended starting doses: (1) patients weighing 100 kg or less, 45 mg SC initially and 4 weeks later, followed by 45 mg administered SC every 12 weeks; (2) patients weighing more than 100 kg, 90 mg administered SC initially and 4 weeks later, followed by 90 mg administered SC every 12weeks
• Recommended alternate dosages are higher doses (90 mg instead of 45 mg in patients weighing ≥100 kg) or with greater frequency (eg, every 8 wk in maintenance phase) if response to standard dosing is inadequate
• Can be used as monotherapy option for adults with moderate-to-severe plaque psoriasis affecting the palms and soles (plaque-type palmoplantar psoriasis), nails, or scalp
• Can be used as monotherapy option for adults with other subtypes (ie, pustular, erythrodermic) of moderate-to-severe psoriasis; evidence is limited for use in inverse and guttate psoriasis
• Recommended as monotherapy option in adults with plaque psoriasis of any severity when associated with psoriatic arthritis
• Can be recommended combination treatment option with topicals (eg, high-potency corticosteroids with or without a vitamin D analogue) to augment treatment of moderate-to-severe plaque psoriasis
• May be combined with acitretin, methotrexate, apremilast, cyclosporine, or narrowband ultraviolet phototherapy for moderate-to-severe plaque psoriasis in adults

Interleukin-17 Inhibitors

Secukinumab recommendations are as follows:

• Monotherapy treatment option in adults with moderate-to-severe plaque psoriasis
• Recommended starting dose of 300 mg by self-administered SC injection at week 0, week 1, week 2, week 3, and week 4, followed by 300 mg every 4 weeks
• Recommended maintenance dose of 300 mg every 4 weeks
• Recommended dose of 300 mg is more effective than 150 mg
• Can be recommended as monotherapy in adults with moderate-to-severe plaque psoriasis affecting the head and neck (including the scalp) or nails
• Recommended as monotherapy option in adults with moderate-to-severe palmoplantar plaque psoriasis
• Can be recommended as monotherapy option in adults with moderate-to-severe palmoplantar pustulosis
• Can be used as monotherapy in adults with erythrodermic psoriasis
• May be used as monotherapy in adults with plaque psoriasis when associated with psoriatic arthritis

Ixekizumab recommendations are as follows:

• Monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended starting dose of 160 mg by self-administered SC injection, followed by 80 mg at week 2, week 4, week 6, week 8, week 10, and week 12
• Recommended maintenance dose of 80 mg every 4 weeks
• Can be recommended as monotherapy option in adults with moderate-to-severe plaque psoriasis affecting the scalp or nails
• Can be recommended as monotherapy option in adults with erythrodermic psoriasis or generalized pustular psoriasis
• Recommended as monotherapy option in adults with plaque psoriasis when associated with psoriatic arthritis

Brodalumab recommendations are as follows:

• Recommended as monotherapy treatment option in adults with moderate-to-severe plaque psoriasis
• Can be used as monotherapy option in adults with generalized pustular psoriasis
• Recommended dose of 210 mg by self-administered SC injection at week 0, week 1, and week 2, followed by 210 mg every 2 weeks

Interleukin-23 Inhibitors

Guselkumab recommendations are as follows:

• Recommended as monotherapy treatment option for adults with moderate-to-severe plaque psoriasis
• Recommended dose of 100 mg by self-administered SC injection at week 0 and week 4, followed by every 8 weeks thereafter
• Recommended as monotherapy option in adults with scalp, nail, or plaque-type palmoplantar psoriasis

Tildrakizumab recommendations are as follows:

• Recommended as monotherapy treatment option in adults with moderate-to-severe plaque psoriasis
• Recommended dose of 100 mg given in office by physician-administered SC injection at week 0 and week 4, followed by every 12 weeks thereafter

Risankizumab is not approved by the FDA, but it can be used as monotherapy in adults with moderate-to-severe plaque psoriasis. When approved, the dose will likely be 150 mg given by self-administered subcutaneous injections at week 0 and week 4, followed by every 12 weeks.

Guidelines on the safe and effective prescribing of oral cyclosporine in dermatology by the British Association of Dermatologists  ^[61]

Cyclosporine is licensed for use in the following indications:

• Atopic dermatitis (in persons aged 16 years or older)
• Psoriasis (in persons aged 16 years or older)

Good evidence supports the use of cyclosporine outside its product license for the following indications:

• Atopic dermatitis (in persons younger than 16 years)
• Behçet disease
• Chronic spontaneous (idiopathic) urticaria
• Graft versus host disease
• Palmoplantar pustulosis
• Pyoderma gangrenosum

Cyclosporine should be used only as a last resort in the following indications, and current evidence shows it is unlikely to be beneficial:

• Alopecia areata
• Discoid lupus erythematosus
• Pemphigus foliaceous
• Pemphigus vulgaris

Continuous treatment may be considered for select patients with chronic skin disease in the appropriate situation; however, in an effort to reduce nephrotoxicity, use single or intermittent short courses of up to 16 weeks if possible. Cyclosporine dose titration during therapy also should be used to reduce nephrotoxicity.

If hypertension occurs, the cyclosporine dose should be reduced and/or the hypertension should be treated. If appropriate blood pressure cannot be maintained, discontinue cyclosporine.

If infection is suspected, consider obtaining consult on the safety of inducing immunosuppression; ensure all necessary treatment is being administered before beginning cyclosporine.

Patients should be advised to seek advice early if febrile illness occurs or their skin condition rapidly worsens.

Owing to a long‐term risk of developing nonmelanoma skin cancer, cyclosporine should not be administered concurrently with phototherapy.

Serum lipid levels should be measured for a baseline and should be monitored throughout treatment; this is especially important in patients considered high risk (eg, diabetics, those with preexisting hyperlipidemia).

Guidelines on the m anagement  and  treatment  of  psoriasis  with  phototherapy  from the  American Academy of Dermatology and the National Psoriasis Foundation  ^[62]

Narrowband ultraviolet B phototherapy

Phototherapy using narrowband ultraviolet B (NB-UVB) is recommended as monotherapy for adults with plaque psoriasis.

For adults with generalized plaque psoriasis, the recommended NB-UVB phototherapy starting dose should be based on the minimal erythema dose or it should be determined based on a fixed-dose or skin-phototype protocol.

For adults with generalized plaque psoriasis, a treatment phase of thrice-weekly dosing of NB-UVB phototherapy is recommended.

For adults with psoriasis, treatment with short-term psoralen plus ultraviolet A (PUVA) monotherapy is more effective than NB-UVB.

Owing to its increased safety, higher convenience, and lower cost, NB-UVB is preferred over PUVA monotherapy for psoriasis in adults, even though it is less effective.

In adults with generalized plaque psoriasis, NB-UVB is recommended over broadband ultraviolet B (BB-UVB) monotherapy.

Treatment with NB-UVB monotherapy is recommended for guttate psoriasis patients, regardless of their age.

For appropriate patients with generalized plaque psoriasis, home-based NB-UVB phototherapy is recommended as an alternative to in-office NB-UVB phototherapy.

Treatment with NB-UVB phototherapy is recommended for pregnant patients who have guttate psoriasis or generalized plaque psoriasis.

As a measure to possibly improve efficacy, NB-UVB phototherapy can be safely augmented with concomitant topical therapy using retinoids, vitamin D analogues, and corticosteroids.

Oral retinoids can be combined with NB-UVB phototherapy in appropriate patients with generalized plaque psoriasis if they have not responded adequately to monotherapy.

Owing to an increased risk of developing skin cancer, long-term combination therapy with NB-UVB and cyclosporine is not recommended for adults with generalized plaque psoriasis.

Apremilast combined with NB-UVB phototherapy can be considered for adult patients with generalized plaque psoriasis if they have not responded adequately to monotherapy.

To reduce the risk of genital skin cancer, all patients receiving NB-UVB phototherapy should be provided genital shielding.

To reduce the risk of ocular toxicity, all patients receiving NB-UVB phototherapy should be provided eye protection with goggles.

Owing to the risk of photocarcinogenesis, use caution when administering NB-UVB phototherapy to patients with a history of melanoma or multiple nonmelanoma skin cancers, arsenic intake, or prior exposure to ionizing radiation.

Folate supplementation is recommended for females of childbearing age who are receiving NB-UVB phototherapy.

To maintain the clinical response from NB-UVB phototherapy, maintenance therapy can be considered.

BB-UVB phototherapy

In adults with generalized plaque psoriasis, BB-UVB phototherapy is recommended as monotherapy if NB-UVB is not available.

In adults with generalized plaque psoriasis, BB-UVB monotherapy is considered less efficacious than NB-UVB or oral PUVA monotherapy.

Monotherapy with BB-UVB may be considered for adults with guttate psoriasis.

To reduce the risk of genital skin cancer, all patients being offered BB-UVB phototherapy should be provided with genital shielding.

To reduce the risk of ocular toxicity, all patients receiving BB-UVB phototherapy should be provided eye protection with goggles.

Owing to the risk of photocarcinogenesis, use caution when administering BB-UVB phototherapy to patients with a history of melanoma or multiple nonmelanoma skin cancers, arsenic intake, or prior exposure to ionizing radiation.

Combination therapy with acitretin and BB-UVB can be considered in adults with generalized plaque psoriasis.

Targeted UVB phototherapy

The recommended targeted UVB phototherapy for adults with localized plaque psoriasis (< 10% body surface area), for individual plaque psoriasis lesions, or for patients with more extensive disease includes excimer 308-nm laser, excimer 308-nm light, and targeted NB-UVB 311- to 313-nm light.

For maximal efficacy, the recommended treatment frequency for targeted UVB phototherapy in adults with localized plaque psoriasis is 2-3 times per week, rather than once every 1-2 weeks.

In adults with localized plaque psoriasis, the initial dose of targeted UVB phototherapy is based on the minimal erythema dose or by a fixed-dose or skin-phototype protocol.

For treating localized plaque psoriasis in adults, the most effective targeted UVB phototherapy is excimer 308-nm laser, followed by excimer 308-nm light, followed by localized NB-UVB 311- to 312-nm light.

For adults with plaque psoriasis (including palmoplantar psoriasis), a recommended targeted UVB phototherapy includes excimer 308-nm laser and excimer 308-nm light.

Treatment of plaque psoriasis in adults with excimer 308-nm laser may be combined with topical steroid therapy.

A recommended targeted UVB phototherapy treatment for adults with scalp psoriasis is excimer 308-nm laser.

PUVA therapy

In the treatment of localized plaque psoriasis in adults, particularly those with palmoplantar psoriasis or palmoplantar pustular psoriasis, topical phototherapy with PUVA is deemed superior to NB-UVB 311- to 313-nm light.

A recommended treatment for psoriasis in adults is oral PUVA.

A recommended treatment for moderate-to-severe psoriasis in adults is bath PUVA.

Photodynamic therapy

Photodynamic therapy with either aminolevulinic acid or methyl aminolevulinate is not recommended for adults with localized psoriasis, including the palmoplantar variety or nail psoriasis.

Grenz ray, climatotherapy, visible light, Goeckerman, and pulsed-dye laser therapies

Evidence is insufficient to recommend grenz ray therapy (long-wavelength ionizing radiation) for the treatment of psoriasis.

Sufficient evidence exists to recommend climatotherapy (temporary or permanent relocation geographically) for the treatment of psoriasis.

Evidence is insufficient to recommend the use of visible light (blue or red) as a more effective treatment for psoriasis, except in nail psoriasis.

Sufficient evidence exists to recommend Goeckerman therapy (coal tar in combination with UVB phototherapy) for the treatment of psoriasis.

Pulsed-dye laser can be considered for nail psoriasis.