B-QuiCK: Treatment resistant atopic dermatitis

Ciclosporin

2.5 mg/kg/day in two divided doses, increased to 5 mg/kg/day if insufficient response

N.B. 5 mg/kg/day can be prescribed initially if atopic dermatitis is very severe.

• Can cause nephrotoxicity so regular renal function and blood pressure monitoring is required, usually monthly. Stop treatment if patients are not adhering to regular monitoring.
• Not suitable for long-term use (generally six months to two years)
• Preferred option for females of child-bearing potential, however, use with care in younger patients with co-morbidities such as hypertension or high BMI
• In practice it is not generally prescribed to patients aged over 40 – 45 years due to increased risk of age-related renal decline
• Hirsutism may limit use
• More rapid onset of action compared to methotrexate, mycophenolate mofetil and azathioprine

Methotrexate (unapproved indication)

Oral 5 – 25 mg, once per week.^* In practice, a dose of 10 – 20 mg, once per week is often prescribed.

• Some formulations and strengths of methotrexate have a funding restriction, including the available oral tablets (2.5 mg and 10 mg): Retail pharmacy-specialist. See NZF for affected formulations and strengths. This means that the medicine will only be funded in the community on prescription by a specialist or with recommendation by a specialist. For further details, see the Pharmaceutical Schedule rules. The definition of a specialist is not specified in the restriction for methotrexate; many primary care prescribers will initiate this medicine in consultation with a dermatologist, however, vocationally registered general practitioners who feel comfortable initiating methotrexate may do so (as the specialist) without seeking input from a dermatologist. The medicine datasheet notes that methotrexate should only be prescribed by physicians with expertise in its use and a full understanding of the risks. The prescriber should also feel confident that the patient will adhere to the once-weekly regimen.
• Highlight differences in the appearance of 2.5 mg and 10 mg tablets, especially when a patient is transferred from one tablet strength to another; prescribe only one strength of tablet at once to avoid accidental ingestion of 10 mg tablets in place of 2.5 mg tablets
• Folic acid (5 mg per week, on an alternate day to methotrexate, e.g. methotrexate Mondays, folic acid Fridays; unapproved indication) should also be prescribed
• Nausea may limit use (subcutaneous administration may overcome this adverse effect)
• Teratogen and possible mutagen – not first choice for females of child-bearing potential or males planning parenthood
• Some severe medicine interactions, e.g. with trimethoprim + sulfamethoxazole, which is often used for infected atopic dermatitis

Mycophenolate mofetil (unapproved indication)

1 – 3 g/day^*

• There is inconsistency between international guidelines as to whether mycophenolate mofetil is recommended for patients with atopic dermatitis. In New Zealand, it is included in local HealthPathways as a medicine that could be trialled, and is listed as an option for one of the pre-requisites in the Special Authority criteria for upadacitinib.
• Teratogen – not first choice for females of child-bearing potential

Azathioprine (unapproved indication)

Normal or high thiopurine methyltransferase (TPMT) activity: 1 – 3 mg/kg/day

Intermediate TPMT activity: 0.5 – 1.5 mg/kg/day

• Requires TPMT to be measured prior to starting treatment. TPMT is an enzyme that metabolises azathioprine (and other thiopurine medicines). The activity of the enzyme can help to predict those at risk of myelosuppression; low activity is associated with higher risk, and therefore a dose reduction is necessary. High activity may require dose up-titration. Azathioprine is usually avoided in patients with low TPMT activity.
• Lower risk in pregnancy than other options
• Increased risk of UV-induced skin cancers with long-term use
• Many medicine interactions, e.g. allopurinol, ACE inhibitors

Dupilumab (IV; Section 29, not funded) is a biologic often used in preference to other conventional systemic immunosuppressants; however, it is neither approved nor readily available in New Zealand.

• Active serious infection, e.g. active tuberculosis^*
• Absolute lymphocyte count < 0.5 × 10⁹/L^*
• Absolute neutrophil count < 1 × 10⁹/L^*
• Haemoglobin < 80 g/L^*
• Severe hepatic impairment
• Pregnancy
• Breast-feeding

• Age ≥ 65 years
• Diverticular disease
• Risk factors for cardiovascular disease or thrombosis
• Diabetes
• Current or past malignancy (except successfully treated non-melanoma skin cancer)
• Concomitant use of potent CYP3A4 inhibitors or inducers, e.g. grapefruit juice, rifampicin
• Chronic or recurrent infection, history of serious or opportunistic infection or predisposition to infection
• Hepatitis B or herpes zoster reactivation
• End-stage renal impairment (no dose adjustment is required for patients with mild to moderate renal impairment; a maximum dose of 15 mg, daily, should be given in severe impairment)