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Latest treatment options for psoriasis

Psoriasis is a chronic immuno-inflammatory disease, affecting 2-3% of the Western population. The prevalence of chronic inflammatory dermatoses, including psoriasis, has increased over the past 30 years, although the reasons for this are uncertain. Although a number of subtypes exists, including for example guttate, pustular and flexural psoriasis, approximately 90% of those affected will have chronic plaque psoriasis. This is characterised by red, scaly and often very well-defined patches, usually on extensor surfaces (eg. elbows and knees) on both sides of the body. It is known that there is a genetic contribution to psoriasis; monozygotic twins show a concordance of 65-72% versus 15-50% in dizygotic twins.3 However exogenous factors including alcohol, drugs (eg. lithium and β-blockers), infections (eg. Streptococcal Group A infection) and trauma (Koebner phenomenon) may also contribute to psoriasis.  In addition to the cutaneous features, psoriasis may also affect joints and there is increasing evidence that it is an independent risk factor for cardiovascular disease. Furthermore, psoriasis can have a significant impact on a patient's quality of life, with some patients rating the impact of skin disease as highly as some major medical diseases, including cancer and heart disease.

Current treatment options 

Current options include topical agents, phototherapy, conventional systemic treatments and biological therapies (Figure 1). The choice of agent is dependent on disease severity, clinical subtype, co-morbidities, and patient preference, as described in UK and European guidelines.8,9 Depending on the combination of these factors, patients may be commenced on a combination of treatments. Treatment goals should be discussed at the outset and regular review may improve patient adherence.  

Topical treatments

Most psoriasis patients (approximately 80%) will have mild or moderate disease for which topical therapy alone may be sufficient. However, even in more severe disease, topical treatments are important adjuncts to, for example, phototherapy and systemic agents including biologics. Their concomitant use can allow a reduction in doses of systemic drugs.10 Patient adherence with topical treatments can be particularly problematic, with non-adherence of up to 39% and up to 95% of patients under-dosing with topical treatments. Box 1 highlights ways to improve patient adherence.

Current topical treatments include: corticosteroids, vitamin D and its analogues, retinoids, calcineurin inhibitors, coal tar and dithranol. For plaque psoriasis, National Institute for Health and Care Excellence (NICE) guidelines suggest topical vitamin D and its analogues - which include calcitriol, the active metabolite of vitamin D, and two vitamin D analogues, calcipotriol and tacalcitol - are used as first-line topical therapy, along with a co-prescribed (but separate) potent topical corticosteroid.8 An initial response is typically seen after two to four weeks. For sensitive areas (eg. face, retroauricular and flexures) a mild or moderately potent topical corticosteroid should be prescribed as first line. If this is unsatisfactory, continuous treatment is required or there is a serious risk of side effects from corticosteroids (sensitive areas are particularly vulnerable to corticosteroid induced atrophy) then topical calcineurin inhibitors (pimercrolimus, tacrolimus) should be considered; although it is recommended that these are initiated by healthcare professionals with “expertise in treating psoriasis”.8 Dithranol has a role in induction of remission in more specialist settings; coal tar may also be used in this setting. Both dithranol and coal tar can be messy and can cause local inflammation or irritation, so supervision by specialist nurses is preferable. Topical retinoid (tazarotene) is not recommended for routine use in UK or European guidelines.

Phototherapy

Ultraviolet radiation therapy is an established treatment that can be used alone or in combination with the topical agents described above. Ultraviolet-B (UVB) is commonly used and is available as broadband or narrowband (311 nm). The latter form uses the most effective wavelength of UVB for the action spectrum (300-313 nm) of psoriasis. Excimer lamps/laser have more recently become available for the treatment of more limited disease. Ultraviolet-A light is used in conjunction with psoralen, a photosensitiser, that can be taken orally or applied topically in a bath. The combination is known as PUVA (psoralen combined with ultraviolet A). Nowadays whole body PUVA is used less often because of concern of skin cancer risk but localised PUVA is recommended for the treatment of psoriasis affecting the palms (palmoplantar pustulosis). Phototherapy is usually carried out in outpatient dermatology units, requiring patients to attend two to three times per week for a total of about 15-30 treatments, which can be inconvenient. Home phototherapy units are available, however their use is limited by cost and potential safety concerns. 

Systemic conventional therapies

Patients with more severe disease, particularly those with joint involvement, often require systemic treatment. These commonly include conventional immunomodulatory agents such as methotrexate and ciclosporin as well as the systemic retinoid acitretin. Fumaric acid esters are used off-licence in certain specialist centres. Methotrexate is recommended as first-line systemic therapy by NICE.8 Ciclosporin is also recommended as first-line in patients requiring rapid or short-term disease control or are considering conception and cannot avoid systemic therapy.8 Acitretin use is complicated by the risks of teratogenicity in females of child-bearing potential and an unpredictable/variable treatment response. It is usually therefore used as a second or third line conventional systemic agent when methotrexate and ciclosporin have failed or cannot be used.

Systemic biological therapies

The treatment of moderate-severe psoriasis has been revolutionised by the advent of biological therapies, which include monoclonal antibodies against tumor necrosis factor alpha (adlimumab, infliximab), a soluble tumor necrosis factor receptor (etanercept) and more recently ustekinumab against interleukin-12/23. Long-term safety of biological agents remains to be established. For this reason, NICE has recommended that all patients all patients in the UK receiving these new therapies for psoriasis should be registered into British Association of Dermatologists Biologic Interventions Register (BADBIR). Biological therapies are expensive, with an average cost per patient of around £10,000 per year. They are considered cost-effective by NICE and are indicated for the treatment of moderate-severe psoriasis that has not responded to at least two conventional systemic agents, as described above, or in whom those agents are contraindicated.8  

Future expectations and research direction

An improved understanding of the pathogenesis of psoriasis 

has lead to the development of potential therapeutics. A wide range of new topical therapies are currently in clinical trials;11 some are new formulations of existing compounds designed to be more cosmetically acceptable (eg. foams, gels and sprays), others are new developments of existing drug classes (eg. 

vitamin D analogues, corticosteroids and calcineurin inhibitors). Topical therapies acting through novel targets are also in clinical trials. Some of these novel targets/pathways have anti-inflammatory effects, for example those acting through nerve growth factor, phosphodiesterase, Janus-associated kinase/Signal Transducer and Activator of Transcription (JAK/STAT), selectins and p38 kinase. 

Other novel targets/pathways have anti-proliferative effects for example those acting through parathyroid hormone and epidermal growth factor. 

Several new oral 'small molecules' are being developed.11 These, unlike earlier oral therapies for psoriasis, selectively target intercellular signalling molecules, including nuclear factor kappa B, phosphodiesterase and janus-associated kinase. Among other roles, these molecules modulate inflammatory pathways often downstream of key cytokines, eg. interleukin-12 (IL-12), IL-17 and IL-23, within cells. 

New biological therapies are also being developed(12);12 currently in clinical trials are monoclonal antibodies against various interleukin cytokines: IL-17 (brodalumab, ixekizumab, secukinumab), IL-22 (fezakinumab) and IL-23 (guselkumab) as well as cluster of differentiation (CD) receptors thought to be important in activating regulatory T cells, including CD4, CD40 and CD162. 

Treatments are listed alphabetically within categories. Treatment choice(s) depends on the interplay of a variety of factors such as disease severity, site(s) affected, co-morbidities (eg. arthritis), patient preference, logistical considerations (eg. ability to attend for phototherapy three times a week), gender, desire to start a family and local resources. Patients may be commenced on a combination of treatments or treatments added to a regime at a later time. Treatments may not be suitable for all patients.