3. Monitoring patients with moderate to severe psoriasis

Patients with moderate to severe psoriasis are usually managed in secondary care with the following treatments:

• Phototherapy: suitable for most patients if topical treatments are not sufficient
• Methotrexate: the preferred oral treatment for patients with chronic plaque psoriasis
• Ciclosporin: typically used after trialling methotrexate
• Acitretin: used if methotrexate and ciclosporin are inappropriate or unsuccessful
• TNF inhibitors: initiated if other treatments are unsuccessful

Clinicians in primary care may provide repeat prescriptions for these treatments. There needs to be a clear understanding between the dermatologist and general practitioner regarding the responsibility for monitoring patients and requesting blood tests; adverse effects of these medicines can be serious and potentially fatal.

Phototherapy is suitable for most patients if topical treatments are not sufficient

Phototherapy is used for patients with moderate to severe chronic plaque psoriasis who have not responded sufficiently to topical treatments.¹ It is most effective for thin plaques on the trunk and limbs.

Narrow band UV-B (NB-UVB) is the preferred form of phototherapy, which involves multiple exposures over six to twelve weeks, that are initially a minute or less and extended over subsequent sessions.^{2, 3} Other forms of phototherapy, such as psoralen with UV-A exposure (PUVA), are no longer preferred treatments for chronic plaque psoriasis but may be used in select patients.

Tanning beds or sun exposure cannot be used as substitutes for phototherapy. They are less effective in the treatment of psoriasis and have a much wider range of wavelengths than NB-UVB phototherapy with a higher risk of skin damage.^{4, 5}

Patients should not apply topical products prior to phototherapy sessions

Patients are advised not to apply topical products such as salicylic acid or sunscreen prior to phototherapy sessions, as they can interact with UV-B treatment. Calcipotriol, if used, should be applied after rather than before treatment, as it is inactivated by UV light.⁵

One-third of patients have adverse effects from phototherapy, but specific monitoring in primary care is generally not needed

Adverse effects of NB-UVB phototherapy include erythema, pruritus, burning, stinging and occasionally blistering of the skin.⁶ Advise patients to report burning or pain following a phototherapy session; the phototherapy team will adjust the dose for future sessions. Painful erythema can be treated with emollients, non-steroidal anti-inflammatory medicines, and a few applications of a mild potency topical corticosteroid.

Treatment with NB-UVB may contribute to the development of wrinkles or telangiectasias.⁶ Encourage patients to be sun smart to mitigate this risk. Photosensitising medicines such as doxycycline should be prescribed with caution or avoided while the patient is undergoing phototherapy. Evidence suggests NB-UVB treatment is not associated with an increased risk of skin cancer, although guidelines recommend increased monitoring if patients have multiple courses.^{1, 5} Patients with recurrent cold sores may experience a flare following phototherapy.⁶

A list of commonly prescribed medicines which are associated with photosensitivity reactions is available at: www.dermnetnz.org/topics/drug-induced-photosensitivity

Continued treatment with topical corticosteroids or calcipotriol may be necessary for plaques that are resistant to phototherapy, or at sites which are difficult to treat, such as the scalp.⁷

Methotrexate is the preferred oral treatment for patients with chronic plaque psoriasis

Low-dose methotrexate, a mild immunosuppressant with anti-inflammatory properties, is the preferred oral treatment for patients with moderate to severe plaque psoriasis, typically prescribed at doses of 15–30 mg weekly, taken as one dose per week.^{7, 8} It is usually initiated by a dermatologist with general practitioners providing follow-up prescriptions, which must have specialist endorsement, for full subsidy.

Monitoring recommendations

Patients taking methotrexate require close monitoring (Table 1) as treatment can cause serious and potentially fatal adverse effects including hepatotoxicity, bone marrow suppression, gastrointestinal bleeding and perforation and haemorrhagic enteritis.^{9, 10} Blood samples should be taken at least five days after the last dose of methotrexate.

Monitoring of HbA_1c and lipid levels is recommended. Evidence shows the risk of hepatotoxicity during methotrexate treatment is increased in patients with obesity, diabetes, or liver conditions such as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease.⁸

Dermatologists may also request that patients have procollagen type 3 (procollagen 3 N-telopeptide) measured, which is a serum marker of hepatic fibrosis.¹¹ Patients with results and risk factors suggestive of liver disease may require referral for liver elastography to detect liver fibrosis, if available. Pulmonary toxicity is less common in patients with psoriasis taking low-dose methotrexate than in patients with rheumatoid arthritis and specific monitoring of lung function is not required; however, inform patients of potential symptoms, such as dry cough, which could indicate pulmonary toxicity.^{8, 12} Bone marrow suppression is rare during low-dose methotrexate treatment; when it does occur, this is often associated with prescribing or dispensing errors, reduced renal function or medicines interactions.¹¹ Other adverse effects of methotrexate include fatigue, nausea and headaches; less commonly, mouth ulcers; and rarely, hair loss.¹³

Safe prescribing of repeat methotrexate prescriptions

Cases of serious toxicity, including deaths, have occurred when methotrexate has been taken daily instead of weekly, often due to prescribing or dispensing errors.

Key points for safe prescribing include:^{8, 9, 14}

• Prescribe methotrexate as a specific weekly dose, rather than “as directed”
• Prescribe 5 mg folic acid, once per week, to be taken at least two days after methotrexate. Methotrexate and folic acid tablets are both yellow.
• Write days of administration out in full on prescriptions
• Prescribe one strength of tablet at a time, where possible. If both 10 mg and 2.5 mg tablets are prescribed, point out to patients the differences in tablets, especially if doses change.
• Warn patients to report symptoms that could indicate:
  • Bone marrow suppression, e.g. fever, sore throat, mouth ulcers
  • Hepatotoxicity, e.g. jaundice, abdominal pain
  • Pulmonary toxicity, e.g. dry cough, dyspnoea
• Methotrexate interacts with many medicines which can result in increased toxicity and serious adverse effects. For example, serious bone marrow suppression can occur due to interaction with folate antagonists, particularly trimethoprim or co-trimoxazole (trimethoprim + sulfamethoxazole).⁸ Check for drug interactions using the NZF interactions checker: www.nzf.org.nz/nzf_1
• Immunisation with live vaccines during treatment should be avoided
• Methotrexate can cause birth deformities and is contraindicated during pregnancy and lactation.^15,16 Whether use in males poses a risk is controversial, however, guidelines and manufacturers advise that both males and females should use appropriate contraception during, and for at least three months following, treatment.^{10, 11}
• Advise patients to limit alcohol intake to no more than one to two standard drinks once or twice a week¹⁰
• Ensure that patients receive clear instructions in written form. A patient information sheet is available from: www.saferx.co.nz/methotrexate-patient-guide.pdf

Discuss with the patient’s dermatologist if their symptoms fail to improve: methotrexate can be titrated according to clinical response, at recommended increments of 2.5–5 mg per week.¹⁰ It may take up to four weeks for a response after increasing doses.¹⁷

For further information on adverse effects associated with methotrexate use, see: www.bpac.org.nz/BPJ/2014/October/safer-prescribing.aspx

Ciclosporin is typically used after trialling methotrexate

For most patients with chronic plaque psoriasis ciclosporin is a second-line oral treatment, after methotrexate.⁷ Ciclosporin can be prescribed by any medical practitioner but is likely to be initiated in secondary care by a dermatologist. For the treatment of chronic plaque psoriasis it is typically taken in short courses of two to four months in doses of 2.5–5 mg per kg per day.^{7, 10}

Monitoring for nephrotoxicity or hypertension

Ciclosporin can cause nephrotoxicity and hypertension and frequent monitoring is recommended, particularly during the first months of use (Table 2). Older patients or those with obesity or diabetes are at an increased risk of nephrotoxicity.¹⁸

Common adverse effects

Adverse effects from ciclosporin use include headache, respiratory symptoms such as cough and rhinitis, musculoskeletal pain or paraesthesia. Hypertrichosis (an increased growth rate of existing hair) occurs in approximately 5% of patients.¹⁷ There is an increased risk of non-melanoma skin cancer in patients taking ciclosporin who have also had psoralen with ultraviolet light (PUVA) treatment.^17,18

Safe prescribing of repeat ciclosporin prescriptions

Key points for safe prescribing include:^{10, 18}

• Check interactions when initiating other medicines: Ciclosporin is metabolised by cytochrome P450 3A4 and interactions can cause changes in ciclosporin concentrations or the concentration of other medicines. The NZF interactions checker is available at: www.nzf.org.nz/nzf_1. Patients should avoid consuming grapefruit or grapefruit juice as this may increase ciclosporin levels.¹⁷
• Patients should not take ciclosporin if they are also undergoing phototherapy¹⁷
• Immunisation with live vaccines during treatment should be avoided. The efficacy of other vaccinations may be reduced.
• Discuss contraception and pregnancy plans with female patients: ciclosporin is not contraindicated during pregnancy but has been associated with adverse pregnancy outcomes. Discuss the use of ciclosporin during pregnancy with the patient’s dermatologist. Use during breastfeeding is not advised as infants require monitoring of blood levels of ciclosporin and regular review for signs of toxicity.¹⁵
• Ask patients to report symptoms of infections, e.g. fever, chills, sore throat, mouth ulcers, as these may take longer to clear or increase in severity while taking ciclosporin. Infections may also indicate leucopenia.
• Ask patients to report symptoms of liver toxicity such as jaundice and abdominal pain

Table 2. Suggested monitoring for patients taking ciclosporin.^{17, 19}

	Pre-treatment	First 3 months		Thereafter
		Every 2 weeks	Monthly	Monthly	Every 2 months
Laboratory investigations *
Full blood count
Creatinine and electrolytes **
Liver function tests
Uric acid
Bilirubin
Lipid profile
Pregnancy test
Clinical examination
Blood pressure

* Measurement of magnesium levels is recommended if patients report muscle cramps.¹⁹

** Reductions in ciclosporin dose are recommended if signs of nephrotoxicity develop, including elevations in serum creatinine of 30% or more within the normal range; discuss these changes with a dermatologist if they occur.^{10, 18}

Table 3. Recommended monitoring for patients taking acitretin^{17, 20}

	Pre-treatment	First 2 months	Thereafter
		Every 2 to 4 weeks	Every 3 months
Lipid profile
Liver function tests
Full blood count
Creatinine and electrolytes *
Pregnancy test	**

* Acitretin use should be avoided in patients with renal impairment¹⁰

** Within two weeks of starting treatment; patients should start taking acitretin on the second or third day of the next menstrual cycle^{10, 20}

Table 4. Recommended monitoring for patients using TNF inhibitors.^{19, 24}

	Pre-treatment	Initially after treatment begins		Thereafter
		4 weeks	12 weeks	Every 3 to 6 months
Full blood count
Liver function tests
Creatinine and electrolytes
Pregnancy test
HIV
Hepatitis B & C
Tuberculosis