Psoriasis Treatment

• Choice of therapy should be individualized based on severity of disease, presence of comorbidities and healthcare services access
• Most patients will undergo multiple simultaneous therapies
• Clinician should become familiar with all treatment options so that the right therapy can be chosen for each individual patient
• Mild or mild-moderate disease can usually be treated by topical therapy alone
• Moderate-severe or severe disease usually requires phototherapy or systemic therapy including biological agents 
• A treatment regimen can be modified to increase efficacy by increasing the dose, decreasing dose intervals, adding a topical agent, adding another systemic agent or changing the drug   
• Treatment goals include a targeted final outcome of PASI ≤2, PGA clear or almost clear, or DLQI<2 
  • Treatment response is achieved if patient attains ≥75% improvement from baseline PASI score
• Assessment of treatment success for fast-acting drugs may be started after induction therapy up until 16 weeks (24 weeks for slow-acting drugs) after initiating treatment 
  • Assessment during maintenance therapy is usually every 8-12 weeks or in intervals following safety monitoring recommendations

The following considerations will influence the choice and frequency of therapy:

• Severity, BSA involved, body region involved
• Effect of psoriasis on quality of life
• Degree of psychological impairment caused by the disease
• Individual factors such as patient's age and weight, presence of comorbidities (eg hepatic disease, inflammatory bowel disease, hypertension, heart failure), plans for conception, treatment preference, likelihood of treatment adherence 
• Goals of therapy, disease phenotype and activity pattern, presence of psoriatic arthritis and outcomes of prior psoriatic treatments
• Risk versus benefit ratio must be considered for each treatment regimen 
• Cost of therapy

Baseline Studies

• Eg complete blood count (CBC) with platelet, creatinine, electrolytes, liver function test (LFT), hepatitis panel screening, latent tuberculosis (TB) screening, human immunodeficiency virus (HIV) screening
• Advised prior to starting, resuming or increasing therapy with systemic and immunosuppressive agents

Vaccinations

• May consider administration of influenza, hepatitis A and B, tetanus-diphtheria and pneumococcal vaccines prior to therapy
• Once treatment is initiated, live vaccines and live-attenuated vaccines should be avoided
• Avoid live vaccinations in infants until 6 months of age if mothers have received biologic therapy beyond 16 weeks’ gestation

 Topical Therapy

• First-line treatment for mild plaque psoriasis

Emollients

• Considered as the standard adjunctive therapeutic approach to the treatment of psoriasis
• Used in combination with other topical treatments
  • One study established that the combination increase the efficacy of corticosteroids and provide better control of psoriasis with lower doses of corticosteroids
• Soften and smoothen the stratum corneum, achieved by a trapping mechanism that decreases the rate of transepidermal water loss
• Patient preference and treatment area will determine formula used
  • Eg Petrolatum, Liquid paraffin, Mineral oils, Glycerine
  • Petrolatum has more occlusive effect but less humectant effect than mineral oil 
• Various emollient products for psoriasis are available. Please see the latest MIMS for specific formulations and prescribing information.

Calcineurin Inhibitors

• Indicated for psoriasis located in facial and intertriginous areas only
• Not generally effective in plaque psoriasis
• Blocks the synthesis of inflammatory cytokines that have an important role in the pathogenesis of psoriasis

Corticosteroids

• First-line treatment for patients with mild or limited psoriasis and for plaque psoriasis
• Have anti-inflammatory, antiproliferative, immunosuppressive and vasoconstrictive effects
• Tachyphylaxis (development of tolerance) leading to decreased efficacy and side effects from long-term treatment may limit use
  • Use judiciously to obtain maximum benefit with minimum side effects 

• Available in different potencies from mild to very high
  • Low to mid potency
    • May be used on the face, intertriginous areas and sites susceptible to atopy 
    • Not to be used at any site for >8 weeks
    • Combination with vitamin D recommended as initial treatment for adults with trunk and/or limb psoriasis
    • Mid potency recommended as initial treatment for scalp, face, flexures and genital psoriasis
  • High to very high potency
    • Highest potency agents were found to be the most effective followed by vitamin D analogues
    • Potent to very potent topical corticosteroids are not advisable for use on the face, flexures and genitals, over 4 weeks, and in children <1 year old
    • Very high potency corticosteroids may be used on areas with thick, chronic plaques

• Choice of product will depend on site of lesion to be treated, age of patient, patient preference, severity of lesions, steroid potency and formulation
  • Scalp: Lotions, sprays, solutions and gels are preferred since they can be rubbed on the scalp
  • Face: Low potency is recommended; avoid potent steroids
  • Body folds: Cream or gel of low potency is recommended
  • Palms and soles: Very potent steroids are typically necessary; only mildly effective

• Flare-up of psoriasis may occur upon discontinuation; corticosteroid therapy should be reduced slowly
• Use as adjunct with agents that are better tolerated; increase potency of corticosteroid during flare-ups and taper down when in remission
• Commonly used in combination with vitamin D analogues, tar, topical retinoid, UV light, or systemic agents
• Advise regular skin examination for all patients having long-term treatment to assess atrophy

Dithranol (Anthralin)

• Recommended for the treatment of mild-moderate psoriasis; effective treatment for large plaque psoriasis
• Commonly used as short-contact therapy (20-30 minutes) in an outpatient setting
• Slows down the proliferation of stem cells and prevents T-lymphocyte activation so that normal keratinization may occur
• Has lower efficacy than more potent topical corticosteroids or vitamin D analogues
• Not suitable for large areas of small lesions, flexure areas or face; may be used on the trunk, limbs only when treatment with other topicals have failed
• Staining and irritating properties may limit use

Keratolytics

• Salicylic acid is the most commonly used keratolytic recommended for mild-moderate psoriasis
• Remove hyperkeratosis, break down, peel off excess scales and soften the psoriatic plaques
• May be used alone or in combination with other forms of therapy (eg corticosteroids and topical immunomodulators)
  • Combination is more effective because of increased skin penetration
  • Salicylic acid in combination with topical steroids may be considered for the treatment of moderate-severe psoriasis involving ≤20% of BSA, including palmar-plantar psoriasis
• Should not be used together with other oral salicylates or before UVB phototherapy

Retinoid

• Tazarotene is a topical retinoid effective in psoriasis
• May be used for the treatment of mild-moderate psoriasis involving ≤10% of BSA, including palmar-plantar psoriasis and nail psoriasis 
• Mediates cell differentiation and proliferation
• Similar efficacy as topical corticosteroids
• Can achieve remission of psoriatic plaques
• Has slow onset of action and when used as monotherapy, skin irritation (retinoid dermatitis) may limit use
• May be combined with topical corticosteroids to enhance therapeutic effects, reduce the local irritation produced by retinoids and reduce treatment duration
• Teratogenic: Should not be used in pregnant women or those planning to become pregnant

Tars

• Effective for use in chronic plaques in mild-moderate psoriasis
• Reduce keratinocyte proliferation by suppressing DNA synthesis, suppresses inflammation and may affect immunological function
• May be used if vitamin D analogue and corticosteroid is ineffective or not tolerated
• May be used alone as a tar bath or applied directly to psoriatic plaques; avoid face and flexures
• Most popularly used as scalp treatment with corticosteroid or combined with UVB (Goeckerman treatment)
• May cause sterile folliculitis; low patient tolerance as most products are messy and odorous
• Many tar preparations in combination with other psoriasis medications are available. Please see the latest MIMS for specific formulations and prescribing information.

Vitamin D Analogues

• Eg Calcipotriene (Calcipotriol), Calcitriol, Maxacalcitol, Tacalcitol 
• Indicated in chronic plaque psoriasis especially for long therapy and for patients with mild-moderate scalp psoriasis
• Tacalcitol or Calcipotriene combined with steroid may be considered in patients with facial psoriasis 
• Inhibit keratinocyte proliferation and enhance keratinocyte differentiation, after binding to vitamin D receptors
• Studies showed more improvement in psoriasis when used in combination with topical corticosteroids than when either agent is used alone

Other Topical Treatments (Alternative Medicine)

• Eg aloe vera, St John's wort, vegetable oils (VGO), virgin coconut oil (VCO)
• May be considered in patients with mild psoriasis without contraindications
• St John's wort should be used with caution in patients undergoing phototherapy
• VGO has more pro-inflammatory effect than VCO 
• When compared to VGO, VCO has more occlusive and humectant effect, diffuses more, has faster penetration on dry, thick, scaly skin for cell repair, and has more anti-inflammatory effect

Systemic Non-Biological Therapy

Indications for Systemic Non-Biological Therapy

• Symptoms cannot be controlled by topical medications or
• Total wellbeing (psychological, physical, social) greatly affected or
• ≥1 of the following:
  • Diagnosed moderate-severe or severe psoriasis or
  • Localized, affected part significantly impaired or distressed or
  • Failure of phototherapy (treatment failure or relapse >50% of baseline within 3 months)

Apremilast

• A small phophodiesterase-4 inhibitor that can inhibit inflammatory response by regulating pro-inflammatory cytokines
• Indicated in adult patients with moderate-severe plaque psoriasis, especially for scalp and palmar-plantar psoriasis, candidates for phototherapy/systemic therapy
• May be used during induction therapy and for long-term therapy
• May be considered if an oral treatment is preferred and patient has inadequate response, intolerance or contraindications to conventional systemic agents
• Studies demonstrated 75% reduction in PASI score at week 16 as compared to the placebo

Ciclosporin (Cyclosporine)

• Inhibits T-cell activation and is a potent immunosuppressant that binds cyclophilin which inhibits calcineurin and blocks proinflammatory signaling
• Reserved for intermittent control and should not be given for >12 weeks unless clinically indicated
• Effective for moderate-severe plaque-type psoriasis, severe recalcitrant psoriasis, and erythrodermic, generalized pustular and/or palmoplantar psoriasis
• First line in treatment of patients with indications for systemic non-biologic therapy and who:
  • Need fast control of disease
  • With palmoplantar pustulosis
  • Need systemic therapy but have plans to have children in the future
  • Had treatment failure after Methotrexate therapy or has disease flare-up while on preexisting systemic therapy
• Combination with topical Calcipotriene and Betamethasone is recommended for the treatment of moderate-severe psoriasis
• Has been used with topical vitamin D analogue or Methotrexate which lowers effective dose of both agents
• Should only be used by experienced practitioners and in patients who have failed topical treatment, phototherapy and other systemic treatments
• If possible, rotate its use with other treatments or use during severe inflammatory flare-ups
• Should only be used for <1 year; long-term use (>2 years) can lead to nephrotoxicity and possible malignancies (eg squamous cell carcinoma and non-melanoma skin cancers)

Corticosteroids

• Systemic corticosteroids are generally not recommended as they can lead to generalized pustular psoriasis and rebound exacerbations; should only be used if absolutely needed
• Intralesional steroids may be considered for unresponsive lesions and areas with very thick lesions on glabrous skin, scalp, nails, palms and soles

Dimethyl fumarate

• Possesses immunomodulatory, antiangiogenesis and antioxidant effects 
• Recommended option in adults with moderate-severe plaque psoriasis who are intolerant, unresponsive or with contraindications to other systemic agents eg Ciclosporin, Methotrexate and Psoralen plus ultraviolet A (PUVA)
• Studies reported significant reduction in PASI score and improvement in quality of life as compared to the placebo
• Side effects like gastrointestinal disturbance and flushing may limit use

Hydroxyurea

• Inhibits DNA replication
• Antimetabolite which can be effective as monotherapy, though less effective than other systemic agents
• Treatment option for patients who fail topical therapies, UVB, or who cannot tolerate PUVA, Methotrexate or other systemic therapies
• Nearly half of patients who show improvement with Hydroxyurea develop bone marrow toxicity with leukopenia or thrombocytopenia
• Avoid in pregnant and breastfeeding women

Methotrexate

• Inhibitor of folate biosynthesis thereby impairs DNA replication; has cytostatic and anti-inflammatory properties
• Antimetabolite that may be used in patients who have failed topical therapies and photochemotherapy
• Most frequently used agent in moderate-severe, recalcitrant and disabling psoriasis (psoriasis covering >10% BSA)
• Highly effective especially for long-term treatment of severe forms of psoriasis including psoriatic erythroderma and pustular psoriasis
• It is recommended to give subcutaneous dosing to patients on oral treatment with suboptimal response and consider it as the initial route of administration in patients with high need
• Combination with topical Calcipotriene is recommended for the treatment of moderate-severe psoriasis
• Combination with NB UVB may be considered for patients with generalized plaque psoriasis
• May be taken with Folate supplements to reduce toxicity
• Side effects like bone marrow depression, hepatotoxicity or pneumonitis may limit use; monitoring of LFTs, CBC and renal profile is recommended
• Avoid in pregnant and breastfeeding women

Mycophenolic acid

• Interferes with T-cell proliferation
• Antimetabolite initially developed for organ transplantation
• Some reports show beneficial effect in psoriasis patients
• Many patients achieve long remissions but may take up to 12 weeks to see maximal effects
• As an immunosuppressant, there is a small risk of developing lymphoproliferative disease and non-cutaneous malignancies
• In patients receiving this drug with other immunosuppressants, pure red cell aplasia has been reported
• Avoid in pregnant and breastfeeding women

Retinoid

• Modulates epidermal differentiation and proliferation and possesses anti-inflammatory and immunomodulatory properties 
• Acitretin
  • Oral retinoid of choice; effective systemic agent that is not immunosuppressive
  • May be used as monotherapy for pustular, erythrodermic and moderate-severe plaque psoriasis
  • Beneficial effect occurs much more slowly when used for plaque and guttate psoriasis but improves dramatically when combined with PUVA and UVB (lower doses of agents are required)
  • May be combined with Calcipotriene, UVB, PUVA, biologic agents
• Highly teratogenic and tend to persist in body tissues
  • Female patients should not become pregnant for 3 years after treatment has been discontinued
• Avoid in patients taking excessive amounts of vitamin A and in breastfeeding women
• Mucocutaneous side effects and dyslipidemia may occur

Sulfasalazine

• Useful in moderate-severe plaque-type psoriasis; effects are less than other systemic agents
• Side effects are common but are not severe and are typically reversible

Tofacitinib

• Interrupts the Janus kinase/signal transducers and transcription signaling pathway activators for cytokine activation
• May be considered for the treatment of moderate-severe psoriasis
• Multiple phase III clinical trials showed 75% reduction in PASI score at week 16 as compared to the placebo, with treatment benefits experienced up to 2 years
• Nasopharyngitis was the most common side effect; serious infections (cellulitis, herpes zoster, urinary tract infection, pneumonia), malignancies (lymphoma, lung cancer, breast cancer), lymphocytopenia and dyslipidemia were also reported

Other Systemic Treatments (Alternative Medicine)

• Eg fish oil (omega-3 oil), curcumin
• Fish oil may be considered as an adjunctive treatment option to topical, oral and phototherapy in chronic plaque psoriasis
• Oral curcumin supplements may be used as adjunctive treatment for psoriasis patients with varying severity

Immunosuppressive/Biological Therapy 

• Considered for patients who have severe disease
  • Severe disease is defined as having a Psoriasis Area Severity Index (PASI) score of ≥10 and a Dermatology Life Quality Index (DLQI) of >10
  • Very severe disease quantified as total PASI of ≥20 and DLQI of >18
• In addition to severity of the disease, the patient should also have one of the following clinical conditions:
  • At high risk or has developed clinically significant drug-related toxicity and alternative standard therapy cannot be utilized
  • Has contraindications to, intolerance/inaccessibility to, and/or failure to respond to phototherapy and standard systemic therapy, eg Methotrexate and Ciclosporin
  • Severe, unstable, life-threatening disease or severe localized psoriasis with significant impairment of function and/or high levels of distress
  • Psoriatic arthritis making the patient eligible for anti-TNF agent therapy
• May be offered as first-line therapy to adults who meet the criteria for biological therapy 
  • A TNF inhibitor or an IL-17 antagonist (except Brodalumab) may be offered as a first-line therapy to patients with both psoriasis and psoriatic arthritis   
• Changing to an alternative therapy, including another biologic agent, can be considered if patient does not meet the minimum response criteria or is initially responsive but loses response, or if biological therapy becomes intolerable or contraindicated
  • May consider dose escalation or interval reduction if with inadequate response to first biologic therapy due to insufficient drug exposure
• Assess patients for cancer risk and infection prior to and during biological therapy; monitor adverse effects during and after biological therapy

Adalimumab

• Indicated in patients with moderate-severe chronic plaque psoriasis who are candidates for phototherapy/systemic therapy
  • Recommended monotherapy for patients with moderate-severe plaque psoriasis affecting nails, and palms and soles (palmoplantar psoriasis), and may be a treatment option in those affecting the scalp
  • May also be considered in patients with erythrodermic or pustular psoriasis and chronic plaque psoriasis
• Human anti-TNF-alpha monoclonal antibody
• Studies showed 80% of patients achieve 75% improvement in the PASI score at week 12
• To increase efficacy in the treatment of moderate-severe plaque psoriasis, the following may be considered:
  • Combination with Methotrexate, topical agents eg corticosteroids with or without vitamin D analogues or narrow band UV phototherapy
  • Combination with Acitretin, Apremilast or Ciclosporin
• Appropriate for long-term continuous use
• Rebound does not usually occur when discontinued; may lose efficacy after reinitiation

Alefacept

• Indicated in adult patients with moderate-severe chronic plaque psoriasis who are candidates for systemic agents or phototherapy but no longer marketed

Brodalumab

• Indicated in adult patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy and unresponsive or lost response to other systemic agents
  • May be a treatment option in adult patients with generalized pustular psoriasis
• Human monoclonal antibody that binds to IL-17 receptor A (IL-17RA) and blocks the biologic activities of IL-17A, IL-17F, IL-17A/F, and IL-17E

Certolizumab

• Indicated in adult patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy   
• May be used as a first-line biologic agent in women planning pregnancy or when a systemic therapy is needed during the second or third trimester 
• A recombinant, pegylated, humanized Fab fragment of an anti-TNF-alpha monoclonal antibody

Efalizumab

• Indicated in patients with moderate-severe chronic plaque psoriasis but no longer marketed due to reports of progressive multifocal leukoencephalopathy

Etanercept

• Indicated in patients with moderate-severe plaque psoriasis
  • Recommended monotherapy for patients with moderate-severe plaque psoriasis affecting scalp or nails and may be a treatment option in patients with inverse, erythrodermic or pustular psoriasis
  • Response is maintained up to 24 weeks in patients with severe chronic plaque psoriasis
  • Disease clearance may be improved when combined with Methotrexate or narrow band UVB phototherapy
• Considered in patients who are unresponsive, intolerant or have a contraindication to other systemic therapies, or where a short half-life is essential 
• A human recombinant TNF receptor p75 fusion protein that inhibits TNF
• Combination with Acitretin, topical agents eg corticosteroids with or without vitamin D analogues, Apremilast or Ciclosporin may be a treatment option to increase efficacy in the treatment of moderate-severe plaque psoriasis

Guselkumab

• Indicated in adult patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
  • Recommended monotherapy in adult patients with nail, scalp and plaque-type palmoplantar psoriasis
• Human IgG1 lambda monoclonal antibody that blocks p19 subunit of IL-23
• Has been found to have better response in patients with inadequate response to treatment with Ustekinumab

Infliximab

• Indicated in patients with moderate-severe plaque psoriasis
  • May be a treatment option for patients with moderate-severe plaque psoriasis affecting the nails, palms and soles (palmoplantar psoriasis), and scalp
  • May be considered in erythrodermic, inverse or pustular psoriasis
• Consider Infliximab for patients with severe disease or when other biologic agents cannot be used or have failed, or where weight-based dosing is important 
• A human murine chimeric monoclonal antibody that inhibits TNF; with high binding affinity and specificity for TNF-alpha
• Has rapid clinical response, highly effective on initial exposure and in severe acute flares
• Combination with Methotrexate or topical agents eg corticosteroids with or without vitamin D analogues, may be a treatment option to increase efficacy in the treatment of moderate-severe plaque psoriasis
• Combination with Acitretin or Apremilast, may be considered to increase efficacy in the treatment of moderate-severe plaque psoriasis
• Variable efficacy after restarting or beyond the first year of continuous use

Ixekizumab

• Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
  • May be a treatment option for patients with moderate-severe plaque psoriasis affecting the nails or scalp and those with erythrodermic or pustular psoriasis
• A humanized IgG4 monoclonal antibody with neutralizing activity against IL-17A

Risankizumab

• Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
• Humanized IgG1 monoclonal antibody that selectively binds to the human IL-23 cytokine's p19 subunit and inhibits its interaction with the IL-23 receptor 

Secukinumab

• Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
  • Recommended monotherapy in patients with moderate-severe plaque psoriasis affecting the nails or those with moderate-severe palmoplantar plaque psoriasis
  • May be a treatment option in patient with moderate-severe plaque psoriasis affecting the head, neck and scalp or in patients with moderate-severe palmoplantar pustulosis
  • May be considered as an option in patients with erythrodermic psoriasis
• A recombinant human monoclonal antibody that binds IL-17A

Spesolimab 

• Indicated for the treatment of generalized pustular psoriasis flares in adults 
• Humanized IgG1 monoclonal antibody that binds to the IL-36 receptor thereby inhibiting IL-36 signaling and preventing proinflammatory and profibrotic pathway activation

Tildrakizumab

• Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
• Humanized IgG1 monoclonal antibody that selectively blocks IL-23 by binding to the p19 subunit

Ustekinumab

• Indicated in patients with moderate-severe plaque-type psoriasis
  • May be a treatment option for patients with moderate-severe plaque psoriasis affecting nails, palms and soles (palmoplantar psoriasis)
  • May be considered in patients with moderate-severe plaque psoriasis affecting the scalp or with erythrodermic or pustular psoriasis
• Considered in patients who are unresponsive, intolerant or have a contraindication to other systemic therapies 
• Human monoclonal antibody that targets IL-12 and IL-23 on the p40 subunit
• Studies showed 67% of patients achieved 75% improvement in the PASI score at week 12
• May be combined with Acitretin, Methotrexate or narrow band UV phototherapy to increase efficacy in the treatment of moderate-severe plaque psoriasis in adults
• Combination with topical agents eg corticosteroids with or without vitamin D analogues, Apremilast or Ciclosporin may be considered to increase the efficacy in the treatment of moderate-severe plaque psoriasis

Alternative Treatments

• Stress reduction techniques (ie meditation), cognitive behavioral therapy and guided imagery as an adjunctive therapy may help improve psoriasis severity
• Hypnosis as a therapeutic adjunct for mild-moderate psoriasis may be considered in highly hypnotizable patients who are willing to undergo this process
• For patients with mild-moderate or chronic plaque psoriasis who are interested in acupuncture, this may be considered as an adjunctive treatment depending on availability and patient preference