Introduction

When considering treatment options for patients with psoriasis it is important to assess the extent and severity of the disease and how much the condition is impacting the patient's life. Psoriasis area and severity index (PASI) should be used to quantify the extent and severity of the skin involvement. The impact of the disease on the patient's quality of life should be measured using a validated questionnaire such as the Dermatology Life Quality Index (DLQI) score or the psoriasis disability index (PDI). The questionnaires embrace all aspects of life including work, personal relationships, domestic situation, and recreational activities.

Patients often wish to know what has caused their psoriasis and are keen for a cure. However, our current understanding of psoriasis is that it is an inherited autoimmune disease that can be suppressed by current therapies rather than cured. Management comprises avoidance of known exacerbating factors (smoking, alcohol), using topical preparations, undertaking phototherapy or photochemotherapy and taking systemic therapy (tablet, S/C, IV). Selection of the most appropriate treatment for each patient should be tailored to the type of psoriasis, their age, comorbidities, social and occupational factors, quality of life, and patient acceptability. Patients with mild disease usually start with topical therapy and/or ultraviolet treatment, if the disease becomes more extensive/recalcitrant they may switch to more potent systemic agents (see Table 3-1 for management options).

Dermatology day treatment units

Dermatology day treatment units (DDTUs) facilitate the management of psoriasis, particularly in relation to topical therapy, phototherapy, and administration of intravenous or subcutaneous injections. Benefits of the DDTU include compliance, monitoring, education, counselling/support and an overall reduction in the patients' stress levels. Less commonly now short-contact dithranol and crude coal tar that can be applied to psoriatic plaques by specialist nurses. Phototherapy is delivered in custom-built cabinets and regular administration of biological therapy can be given by specialist nurses in IV suites. These day units have almost completely excluded the need for in-patient admissions except for unstable/erythrodermic disease.

National Institute for Health and Care Excellence(NICE) Guidelines on the management of psoriasis can be found online. The principles of treatment are to discuss the diagnosis and treatment options with the patients. Use the Physicians/Patients Global Assessment scores, or PASI/DLQI (as outlined below) to give a measure of disease severity, to assist in deciding on the best treatment option for the patient and to assess efficacy of treatments given. NICE recommend reviewing adults after four weeks and children after two weeks of initiating treatment.

Psoriasis Area and Severity Index (PASI) Score is a validated tool for assessing and documenting the extend and severity of a patient's psoriasis. This can be calculated prior to and following treatments. The full PASI scoring system can be accessed online and in mobile phone apps. But the basic principle is to assess the erythema, scaling and thickness of plaques and the % involvement of each site (head, upper limbs, trunk, lower limbs) to generate a total score. To qualify for systemic/biological therapy most patients would need to have a PASI score of 10 or greater.

Dermatology Life Quality Index (DLQI) Score is a validated questionnaire developed in 1994 at Cardiff university for assessing the impact of skin conditions on a patient's quality of life. A copy can be assessed online with instructions and conditions of use. The questionnaire consists of 10 questions relating to how the patients skin condition is affecting their activities of daily living, psychological well-being, treatment issues etc. The higher the score, the more the skin condition is adversely affecting the patient's quality of life. It is a very useful tool to use in addition to the PGA/PASI for assessing management needs and outcomes.

Topical treatment

Topical treatments are those applied directly to the skin surface, including ointments, creams, gels, tars, lotions, pastes, and shampoo. The topical approach to therapy results in changes at and just below the skin surface (epidermis and dermis). Conventionally, topical medicaments are applied directly to the diseased skin only, in contrast to moisturisers (emollients), which are usually applied more freely. In general, combination therapy is more effective than monotherapy, and change of therapy is superior to continuous usage. The following are the advantages of topical treatments:

• local effects only
• self-application
• safe for long-term use
• relatively cheap.

The following are the disadvantages of topical treatments:

• time consuming in extensive disease
• poor compliance (insufficient amounts and frequency)
• messy and may affect clothing/bedding/hair
• no benefit for associated joint disease
• tachyphylaxis (become less effective with continuous use).

The majority of psoriasis patients with mild to moderate disease can be managed in the community by their general practitioner. Patients should be reviewed after four to six weeks of treatment to assess efficacy, if progress is insufficient despite concordance then second line treatment should be considered. Patients with very extensive, recalcitrant, or unstable psoriasis and associated severe arthritis are usually managed in specialist dermatology centres.

Emollients act as a barrier to cutaneous fluid loss, relieve itching, and help replace water and lipids and therefore restore the barrier function of dry skin. Patients can purchase these over the counter, and personal preference/acceptability usually guide their choice. Regular application of emollients should be encouraged in all patients with dry/flaky skin.

Coal tar (produced by distillation of bituminous coal) preparations are available for purchase over the counter and include ointments, pastes, paints, soaps, solutions, and shampoo. Coal tar is keratoplastic (normalises keratinocyte growth patterns), antipruritic (reduces itch), and antimicrobial. It can be used on stable chronic plaque psoriasis but will irritate acute, inflamed skin. Coal tar in combination with salicylic acid may be more effective for very thick plaques.

Ichthammol (ammonium bituminosulfonate) is a distillation of sulfur-rich oil shale. It has anti-inflammatory properties and is therefore suitable to be used on 'unstable' or inflamed psoriasis. Various preparations can be purchased over the counter including ichthammol ointment.

Dithranol (anthralin, Goa powder), originally derived from araroba trees, is now produced synthetically. Irritation and burning can occur if applied to normal skin; therefore, careful application to psoriatic plaques is needed (Figure 3-1). Normal skin can be protected with petroleum. Dithranol short/long contact temporarily stains the skin/hair a purple-brown colour. Dithranol creams can be applied to plaques for 30 minutes and then washed off. The strength is gradually increased from 0.1% to 3% as necessary. Strengths up to 1% can be purchased over the counter, whereas higher concentrations are available by prescription only.

Calcipotriol and tacalcitol, vitamin D analogues, are calmodulin inhibitors used topically for mild or moderate plaque psoriasis. Mild irritation can be experienced and after continuous use, a plateau effect may be encountered with the treatment becoming less effective after an initial response. These preparations are therefore best used in combination with other topical agents. It is important not to exceed the maximum recommended dose as there is a risk of altering calcium metabolism.

Corticosteroids in topical formulations are an important adjuvant to the management of patients with psoriasis; these are prescription-only preparations (except very mild steroids) and can be supervised by the general medical practitioner. Corticosteroids help reduce the superficial inflammation within the plaques. However, relapse usually occurs on cessation and tachyphylaxis is observed. Tachyphylaxis is thought to result from tolerance to the vasoconstrictive action of corticosteroids on cutaneous capillaries. Topical steroids should be applied to the affected areas of skin only once or twice daily. Manufacturers suggest topical steroids should be applied sparingly but this is difficult for patients to quantify; therefore, practitioners advise the use of finger-tip units (FTUs) as a guide. When the steroid ointment/cream is squeezed out from a tube, it comes out in a line, and the quantity between the finger-tip and the first skin crease is 1 FTU (approximately 500 mg) enough to cover a hand-sized area of skin (back and front of the hand).

The strength of topical steroids is graded from mild to very potent. Prolonged use of very potent topical steroids should generally be avoided in the treatment of chronic skin diseases such as psoriasis. Mild/moderate topical steroids are safe to use on the face and flexural skin, and in erythrodermic disease. Moderate or potent preparations can be used on chronic stable plaques on the body. Combination products seem to be among the most effective in the treatment of psoriasis, especially those containing salicylic acid, vitamin D, tar, and antibiotics. Systemic corticosteroids should not be used to treat psoriasis.

Scalp psoriasis

Scalp psoriasis affects approximately 50% of patients; it can be one of the earliest skin sites affected. Scalp psoriasis is often difficult to treat because of the thick nature of the scales, inaccessibility of the skin (owing to hair getting in the way) and the difficulty of self-application of treatment (Figure 3-2). Most patients need to treat the scalp regularly. Initially, products are rubbed into the affected scalp skin and left on overnight (combinations of tar, salicylic acid, sulfur, and emollient are used), and then washed out with tar-based shampoos; then steroid/salicylic acid/vitamin D-containing scalp applications/gels are applied to the underlying inflamed skin. This sequential and combination approach to scalp treatment is often successful if maintained. Treatment in the DDTU can be immensely helpful in the management of severe scalp psoriasis for patients who find it difficult to undertake this treatment themselves at home.

Ultraviolet treatment - phototherapy and photochemotherapy

The mechanisms of action of phototherapy are complex. Evidence suggests that phototherapy reduces the antigen-presenting capacity of dendritic cells, induces apoptosis of immune cells and inhibits synthesis and release of pro-inflammatory cytokines. The resultant cutaneous effects are those of topical immunosuppression and a reduction in dermal inflammation and epidermal cell turnover.

Phototherapy and photochemotherapy should be delivered in specialist dermatology units. It is suitable for psoriasis patients with extensive disease that has not cleared with topical therapy (Figure 3-3). Patients must be able to attend the phototherapy suite two to three times weekly on a regular basis for approximately six to eight weeks. Contraindications to treatment include a history of previous skin malignancy and photosensitive diseases such as lupus, porphyria, albinism, and xeroderma pigmentosum. A full drug history should be taken to ascertain whether the patient is taking any photosensitising medication.

Phototherapy is usually delivered in vertical irradiation units (Figure 3-4). The dose and time of exposure to light is gradually increased as the treatment progresses. Patients apply a layer of emollient to their skin before standing inside the cabinet (this helps remove surface scale and aids UV penetration), they wear UV protective goggles (to protect against corneal keratitis and cataract formation) and 'sanctuary sites' (genitals) are covered.

There is an increased risk of developing cutaneous malignancies with increasing cumulative doses of phototherapy. How much phototherapy can be given safely will depend on the patient's skin type and cumulative dose of UV received. In addition to the increased risk of cutaneous malignancy, premature ageing of the skin and multiple lentigines can result.

Current estimates suggest that patients can be given approximately 200 individual treatments (1000 J) of light safely within their lifetime. Consequently, an individual patient's light 'quota' can soon be used up with a standard course comprising 20-30 treatments (Figures 3-5 and 3-6). Maintenance treatment with phototherapy is rarely now given for psoriasis. The total cumulative dosage is carefully monitored and kept as low as possible to reduce the risk of side effects.

Two main types of phototherapy are currently available, broadband ultraviolet B (UVB) and narrow-band ultraviolet B (TL01) and photochemotherapy ultraviolet A plus psoralen (PUVA). UVB phototherapy has advantages over PUVA as it can be used in children, during pregnancy and does not require the wearing of UV-blocking glasses pre/post-treatment.

Ultraviolet B (UVB)

UVB is short wavelength ultraviolet light and is administered three times weekly, (20-30 treatments) for widespread psoriasis. Conventional broadband UVB lamps emit wavelengths from 280 to 330 nm; these machines are largely being superseded by TL01 devices which emit ultraviolet light at 311 nm. TL01 is more effective than broadband UVB and there is a reduced risk of burning. The starting dose and subsequent increments (mJ/cm²) for patients is usually based on measuring the MED (minimal erythema dose), which is the dose of UVB just sufficient to cause erythema (the patients starting dose will then commence at 70% of the MED for psoriasis). UVB can be given in combination with tar (Goeckerman regimen) or dithranol (Ingram regimen) for chronic thick plaques of psoriasis. UVB in combination with oral acitretin can also increase the efficacy.

Ultraviolet A (UVA)

UVA is long-wavelength ultraviolet light (320-400 nm) and is given in combination with oral or topical psoralen (PUVA) twice weekly (20-30 treatments) for recalcitrant widespread thick plaque psoriasis. There are two types of psoralen tablets: 8-methoxypsoralen (8MOP) 0.6 mg/kg body weight and 5-methoxypsoralen (5MOP) 1.2 mg/kg taken two hours before treatment. 8-MOP is associated with a higher incidence of side effects such as nausea, vomiting, pruritus, and erythema and is consequently less commonly used than 5MOP. The MPD (minimum phototoxic dose) or skin phototype is used to determine the starting dose of UVA and the subsequent increments used (J/cm²). Protective goggles are worn during UVA exposure and sunglasses for 24 hours post oral psoralen ingestion. Topical psoralen (bath PUVA) is less frequently delivered than oral psoralen. Localised PUVA (using psoralen gel) can be used to treat palmo-plantar psoriasis (Figure 3-7).

Systemic treatment

Systemic therapy for severe psoriasis should ideally be managed by experienced specialist dermatologists. Candidates for systemic therapy include patients with unstable inflamed psoriasis, those with widespread disease (Figure 3-8) that have failed to respond to topical/phototherapy regimens and concomitant psoriatic arthropathy. The first-line systemic agents in most dermatology centres are acitretin, ciclosporin, and methotrexate. Alternatives include hydroxyurea, azathioprine, and mycophenolate mofetil (MMF). Biological therapies (infliximab, etanercept, ustekinumab, adalimumab, secukinumab, ixekizumab) can be considered if patients have failed to respond to first-line agents or suffered side effects precluding the continued use of at least two systemic agents (UK guidelines).

Methotrexate

Methotrexate may be suitable to treat unstable erythrodermic/pustular psoriasis in the acute setting (but onset of action is slow) and is usually used to treat chronic stable plaque disease and psoriatic arthritis. Methotrexate reduces epidermal cell turnover by the inhibition of folic acid synthesis during the S phase of mitosis. Methotrexate is given once weekly as a tablet or injection. Conventionally, patients are started on low doses that are then increased until the psoriasis is 'sufficiently controlled' rather than cleared. Maintenance doses of 7.5-25 mg weekly are usually adequate.

Adverse effects - Methotrexate can be hepatotoxic; therefore, liver function tests must be done prior to and during therapy. Once patients are established on a dose, blood monitoring can be done every 8-12 weeks. Routine liver biopsies for monitoring potential liver fibrosis are no longer indicated. Serum levels of procollagen III (an indirect marker of liver fibrosis) is being superseded by a non-invasive transient elastography (FibroScan®) of the liver which assesses hepatic stiffness and hence the degree of liver fibrosis. It is likely that FibroScan will become more widely available and used first line for liver assessment in patients with psoriasis taking methotrexate

Myelosuppression can occur in patients taking methotrexate, and its onset may be rapid or insidious. Patients should be monitored with regular full blood counts (FBCs). An initial test dose of 5 mg should be given on commencement of methotrexate followed by a FBC one week later to ensure that there is no idiosyncratic marrow suppression. Folic acid supplements should be given (at least 5 mg weekly, taken on a different day to the methotrexate). Methotrexate is excreted in the urine; therefore, the dose must be reduced in renal impairment. Aspirin and sulfonamides diminish plasma binding. Interactions occur with several drugs including barbiturates, phenytoin, oral contraceptives, and colchicine.

Acitretin

Acitretin is a vitamin A derivative that is effective in treating chronic plaque psoriasis with approximately 70% clearance in eight weeks. A synergistic effect has been observed with concomitant PUVA, when patients require less UV exposure to clear their psoriasis.

Adverse effects - most patients experience mucocutaneous symptoms including drying of the mucous membranes, crusting in the nose, itching, thinning of the hair, and erythema of the palms and nail folds. These are usually not severe and settle when treatment stops.

Hepatotoxicity and raised lipid concentrations occur in 20-30% of patients. Liver function tests and cholesterol/triglyceride concentrations should be carefully monitored every three months once patients are established on the treatment. Acitretin can be metabolised to etretinate (half-life 70-100 days) which is teratogenic and therefore women during reproductive years must use effective contraception during treatment and for three years afterwards.

Ciclosporin A

Ciclosporin A is an immunosuppressant widely used following organ transplantation. It is effective and suitable for the treatment of inflammatory types of psoriasis because of its rapid onset of action. Patients are given 3-5 mg/kg/day in two divided doses either for short courses or continuous use up to two years maximum. The minimum dose required to control the psoriasis should be used.

Adverse effects - include renal impairment and hypertension. Baseline blood tests should include serum creatinine, urea, electrolytes and glomerular filtration rate, and urine analysis. Monitoring of bloods/urine should then be undertaken every 4-12 weeks. Hypertension may be managed by reducing the dose of ciclosporin or by giving the patient nifedipine. Transient nausea, headaches, gum hypertrophy, and hypertrichosis may also be observed. Hepatic metabolism of ciclosporin (via cytochrome P450) can be inhibited or induced by many different drugs. Medications inhibiting ciclosporin metabolism include erythromycin, itraconazole, verapamil, and diltiazem. Medications increasing ciclosporin metabolism include rifampicin, phenytoin, and carbamazepine.

Mycophenolate mofetil (MMF)

MMF is usually used as a second line systemic agent for treating psoriasis and psoriatic arthritis. It is an immunosuppressant medication that selectively inhibits activated lymphocytes. Studies have shown that about two-thirds of patients taking MMF (2-3 g/day for 12 weeks) have a significant reduction (50%) in their PASI score by 12 weeks.

Adverse effects include gastrointestinal upset and myelosuppression, haematological malignancies, and opportunistic infections. Blood testing for FBC should be undertaken every one to two months for the first year, then every three to four months once established.

Biological therapy

Biological therapy refers to substances originally derived from living organisms such as proteins or antibodies that are designed to block particular molecular steps in the biological pathway that leads to psoriasis. Our greater understanding of the pathophysiology of psoriasis has been exploited to direct treatments against specific cytokine/cell pathways dysregulated in disease. Psoriasis is a T-cell mediated disease and cytokines such as tumour necrosis factor alpha (TNF-) and interferon gamma (INF-) play a role. Biological therapies are currently directed against T-cells or specific inflammatory mediators such as TNF.

The main biological agents currently used to treat severe psoriasis are infliximab, etanercept and adalimumab, ixekizumab, secukinumab, and ustekinumab. Clinical guidelines (NICE - National Institute of Clinical Excellence (UK)) exist in most countries to direct the usage of biological agents in patients with psoriasis. These novel agents are expensive and can result in chronic immunosuppression, leading to fatal infections or tumours, and therefore their usage should be managed in specialist units by experienced practitioners. Biological agents are usually administered S/C or IV by injection/infusions, with frequencies varying from twice weekly to once per month, in either continuous or intermittent regimes. Biological treatments are delivered either at home by the patients themselves/visiting practitioner or are delivered in IV suites based in the community/local hospitals.

NICE guidelines (UK) for the use of biological agents for psoriasis indicate that biological therapies can only be considered in patients with a PASI score of greater than 10 (or significant localised disease at high-impact sites - hands/genitals/scalp) and a DLQI score >10, plus the patient has failed to respond to two conventional systemic agents/phototherapy (contraindicated, non-response or stopped due to unacceptable side effects) or have severe/unstable/life-threatening disease. Biological therapy can also be very useful in treating acute unstable pustulating psoriasis (Figure 3-9).

NICE guidelines (UK) for use of biological agents for psoriatic arthritis indicate that they can be used in severe active disease in patients with at least three tender joints and three swollen joints who have not responded sufficiently to two other disease-modifying drugs.

Many patients starting biological therapy have experienced significant, extensive and recalcitrant psoriasis/psoriatic arthritis for many years prior to their disease being controlled with a biological agent, and consequently they find disease relapse on stopping biologics more unacceptable than ever, as their expectation has now shifted to virtually clear skin and no joint pains. Many studies now are aiming for PASI 90/100 as the criteria for 'disease response' so both patient and physician expectations of biological agents are increasing.

Etanercept

Etanercept (Enbrel®) is a genetically engineered anti-tumour necrosis factor receptor (anti-sTNF) biological agent. Dosing is twice weekly with either 25 or 50 mg given by S/C injection. The higher dose seems to be more effective than lower doses, especially in patients who weigh more than 70 kg. Onset of action is relatively slow, with clinical improvement being observed in the majority of patients between four and eight weeks. Patients may initially have courses of treatment lasting 12 weeks; at that stage an assessment of efficacy should be made (as judged by a reduction in the patient's PASI and DLQI scores); however, continuous therapy may ultimately be needed due to significant disease relapse within three months of stopping treatment. The cost of twice weekly 25 mg or once weekly 50 mg etanercept/patient/year is about £7500 (2017). However, with the introduction of 'Biosimilars' competition is starting to drive prices down.

Adverse effects associated with etanercept include an increased risk of infections, particularly latent TB, and hepatitis B and septicaemia, gastrointestinal symptoms, hypersensitivity and injection site reactions, blood disorders, and a lupus-like antibody-driven syndrome.

Infliximab

Infliximab (Remicade®) is an anti-TNF human-murine monoclonal antibody for the treatment of severe psoriasis/psoriatic arthritis. Infliximab has a rapid onset of action - usually within two weeks in the majority of patients. Doses are calculated according to the patient's weight, 5 mg/kg given by an intravenous infusion at weeks 0, 2, 6, and then every 8 weeks. Nearly 80% of patients experience significant improvement in the extent and severity of their disease (reduced PASI and DLQI scores) by 10 weeks, which is usually maintained for at least 6 months. There is evidence from studies (data up to one year) that continuous therapy is superior to intermittent treatment. Almost 20% of patients develop antibodies to infliximab (possibly due to the presence of murine proteins), which is clinically associated with reduced efficacy. However, the risk of antibody development seems to be reduced when infliximab is given continuously and when it is given with methotrexate in patients with psoriatic arthritis. The total cost of infliximab maintenance treatment for 1 year/patient in the United Kingdom is about £12 500 (2017).

Adverse effects - as above for etanercept; however, in addition, chest pain, dyspnoea, arrhythmias, demyelinating disorders, sleep disturbance, skin pigmentation, gastrointestinal haemorrhage, seizures, and transverse myelitis have been reported, among others.

Adalimumab

Adalimumab (Humira®) is a human anti-TNF monoclonal antibody used to treat severe psoriasis and psoriatic arthritis. It has a fast onset of activity, usually within two weeks and is highly effective in 60-70% of patients. The majority of patients receive 40 mg of adalimumab fortnightly by S/C injection (following a loading dose of 80 mg at week 0). Efficacy is assessed at 16 weeks before deciding whether to continue with the treatment; however, a small cohort of patients with slow/partial response may receive weekly injections, rather than discontinuation. There is some evidence to suggest that continuous therapy is more effective than intermittent therapy. Anti-adalimumab antibodies develop in about 8% of patients, which correlates with reduced efficacy. Some patients with psoriatic arthritis take methotrexate plus adalimumab, which seems to be more effective than adalimumab alone. The cost of fortnightly adalimumab/patient/year was about £9300 in the United Kingdom (2017) and £3000 in 2019 (since the introduction of biosimilars).

Adverse effects - as for etanercept, plus stomatitis, cough, paraesthesia, rash/pruritus, arrhythmias, chest pain, flushing, flu-like symptoms, sleep disturbance, electrolyte disturbances, alopecia, and demyelinating disorders among others.

Ustekinumab

Ustekinumab (Stelara®) is a human monoclonal antibody that targets the p40 subunit of interleukin-12 (IL-12) and IL-23, which prevents them from binding to T-cells and therefore impairs the inflammatory cascade in psoriasis. Because Ustekinumab has only been in clinical use for a few years there is less long-term safety and efficacy data than the other biologic agents. The recommended dose of Ustekinumab is 45 mg (patient weighs 100 kg) or 90 mg (patient weighs > 100 kg) by S/C injection at weeks 0, 4, and then every 12 weeks. Efficacy should be assessed at 16 weeks and only continued in those who have achieved a 75% reduction in their PASI score or 50% reduction in PASI plus 5 point reduction in DLQI scores. The cost of 45 or 90 mg for any individual patient is the same in the United Kingdom as supplied by the manufacturer. Nonetheless, the total cost of Ustekinumab/patient/year in the United Kingdom is around £9300 (based on 4.3 injections/year in 2017).

Adverse effects - as for etanercept, plus allergic reactions (urticarial, angioedema, difficulty breathing), infections, mouth ulcers, haematuria, gastrointestinal symptoms, cough, chest pains, seizures, and visual disturbance.

Ixekizumab

Ixekizumab targets interleukin-17A, a cytokine that promotes keratinocyte proliferation and activation. It is licensed for the treatment of moderate/severe psoriasis (PASI >10, DLQI >10) that has not responded to conventional treatments. The first dose is usually given as 160 mg, (two 80 mg pre-filled 'Pen-syringes'), then 80 mg every other week, at weeks 2, 4, 6, 8, 10, and 12. Treatment efficacy is usually assessed at 12 weeks and if deemed effective (>PASI 75 improvement) then patients usually have one 80 mg injection every four weeks. 78-90% of patients treated with the monoclonal antibody either every four weeks or every two weeks achieved at least a 75% reduction in PASI score at 12 weeks. Adverse effect profile is similar to the other biologics in terms of immunosuppression. Ixekizumab is known to exacerbate inflammatory bowel disease, may cause angioedema and antibodies can develop to the drug. The white cell and the platelet counts need careful monitoring. The annual cost of treatment is estimated to be £17 500.

Secukinumab

Secukinumab is a recombinant human monoclonal antibody that selectively binds to cytokine interleukin-17A and inhibits the release of pro-inflammatory cytokines and chemokines. It is licensed to treat moderate to severe psoriasis (PASI >10, DLQI >10). The usual dose is secukinumab 300 mg (two 150 mg injections) given by subcutaneous injection at weeks 0, 1, 2, 3, and 4, then once/month maintenance. The most common adverse events in studies were upper respiratory tract infections or rhinitis and reactivation of herpes simplex virus. Annual cost for the first year of treatment would be around £30 000, then for maintenance around £25 000/year (2017). Costs may vary according to locally negotiated procurement discounts.

Apremilast

This is a relatively new oral medication for treating moderate to severe psoriasis in patients who have failed to respond to conventional systemic treatment such as methotrexate/ciclosporin and where appropriate acitretin. Apremilast inhibits phosphodiesterase 4 (PDE4) which down-regulates the expression of cytokines and mediators associated with psoriasis (including TNF and interleukin -23). Patients initially start with 10 mg daily and titrate up to 30 mg BD over five days, they then stay on this dose. Cost of the medication is about £6500/year. Studies show that just over 50% of patients achieve a PASI 50 by four months. Main side effects include diarrhoea, nausea, and headache.