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Table 2. Characteristics of systemic agents Drug Mechanism of action Efficacy Potential undesirable effects

Acitretin Not fully understood / Inhibits IL-6

15 % Cheilitis, xerosis, nosebleeds, alopecia, known teratogen

Adapted from Lancet 2015; 386:983 – 94; and Journal der Deutschen Dermatologischen Gesellschaft 2012; 10( suppl 2): S1 – 95.

Biologic

Systemic agents

Phototherapy( UVB)

Topicals

Figure 5. A stepwise approach to psoriasis treatment

Adapted from Rubel, D. Specialty practice series: The role of biologic agents in the treatment of severe psoriasis [ online ]. AJP: The Australian Journal of Pharmacy 2013; 94:68-71.

Figure 6A. Pre-UVB therapy.

Figure 6B. Post-UVB therapy.

PBS requirements for prescribing biologics

IN order to receive a biologic a patient must:

• Have psoriasis that has persisted for more than six months with a PASI greater than 15 and has failed to respond to three of the following four conventional therapies: UVB, methotrexate, cyclosporine, and acitretin

OR

• Have contraindications to or defined toxicity-related adverse reactions to other systemic therapies

A STEPWISE approach, as shown in figure 5, can be used when managing psoriasis.

The first-line management of psoriasis is topical therapy. Some 70-80 % of patients with psoriasis can be controlled with topical therapies. 2

These include topical corticosteroids, tar preparations, salicylic acid, vitamin D analogues( calcipotriol), topical retinoids( tazarotene) and calcineurin inhibitors( tacrolimus / pimecrolimus). 8

Salicylic acid and emollients are often used in combination with topical therapies to help reduce scale and assist in penetration of topical therapies. 9

Topical corticosteroids and vitamin D derivatives are based on level 1 evidence, and exhibit 60 % and 45 % PASI-75 efficacy respectively when used as monotherapy in mild psoriasis. 2 The current Australian Therapeutic Guidelines recommends using tar preparations, often in combination with corticosteroids and vitamin D analogues as maintenance options to achieve better control. 10

Light therapy, including ultraviolet B( UVB) and psoralen with ultraviolet A( PUVA) are backed by level 2 evidence, and UVB is the next treatment option recommended by the Australian Therapeutic Guidelines. 2, 10

Narrowband UVB( nUVB)( 311nm) is the standard of treatment and has advantages over broadband UVB( 280-320nm) and PUVA. 11

Narrowband UVB is considered superior to other light therapies because of its safety and efficacy profile. 11 PUVA and nUVB exhibit 90 % and 70 %( respectively) PASI- 75 efficacy rates, but can be more beneficial when used with topical therapies. 2

A potential limitation to using light therapies is that numerous doses per week administered at a clinic may not always be feasible for all patients. Patients and healthcare staff need to be aware of possible acute adverse reactions including erythema, blistering and hyperpigmentation.

Skin malignancies are a potential side effect of PUVA, and this treatment is no longer administered by most dermatologists in Australia for chronic plaque psoriasis.

Conversely, there have been no data to suggest that nUVB is associated with increased risk of cutaneous malignancy, but caution is advised in patients with fair skin, and a personal or family history of cutaneous malignancy. 2, 10

Until recently, non-biological systemic therapies have been the mainstay of treatment of severe psoriasis.

Methotrexate is often used as a first-line systemic therapy. It is supported by level 2 evidence, and has 50 % PASI-75 efficacy at week 16. 2 Though it can be prescribed in general practice, current recommendations suggest starting methotrexate be done in conjunction with( or directly by) a specialist. 10

Methotrexate is a cytotoxic drug, and works in psoriasis by exerting both immunomodulatory and anti-inflammatory effects( slowing epidermal proliferation), rather than acting as an immunosuppressive. 12 As such, precautions such as excluding pregnancy and infections, and checking of vaccination status and drug interactions, must be taken.

To counter some of the known side effects, folic acid is prescribed concurrently, to be taken weekly on a different day. FBCs and liver and kidney function need to be regularly monitored( approximately three-monthly after the initial dose stabilisation, and more frequently

10, 12

if dosage is escalated).

Australian experience shows that most treatment-induced liver toxicity issues are related to underlying non-alcoholic fatty liver disease. 12

Another option for systemic treatment is acitretin, an oral retinoid that has antiproliferative and anti-inflammatory effects. It shows a 15 % PASI-75 efficacy after 12 weeks, and recommendations are based on level 2 evidence. In practice, the efficacy may be higher, particularly when combined with topical therapies and nUVB.

As it is a highly teratogenic drug, prescription is restricted to specialists. Pregnancy is an absolute contraindication, and should be avoided for two years following cessation of therapy. 10 Lastly, the immunosuppressive qualities of cyclosporine also make it a valid option to systemically treat psoriasis.

Level 1 evidence suggests cyclosporine has 50-70 % PASI-75 efficacy at 12 weeks. 2 Prolonged cyclosporine use is to be avoided because of concerns of nephrotoxic side effects, hypertension, and increased infection and malignancy risk.

Despite treatment with these systemic agents, either as monotherapy or in combination with topical agents, psoriasis can persist in a significant proportion of patients. For these patients with severe recalcitrant disease, the relatively recent introduction of the biological class of medications has entirely changed the scope of treatment.

However, as mentioned above, it is vital that PASI scores be recorded after treatment with nonbiologic agents in order to access biologic treatment through the PBS.

The biological class of drugs are cont’ d next page

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