September 2022 New listing

Apremilast is an immunosuppressant taken as an oral tablet.⁴ It inhibits phosphodiesterase 4, which reduces the production of pro-inflammatory cytokines (ie, TNF‑alpha, interleukin‑17, interleukin‑23), and increases anti-inflammatory cytokines such as interleukin‑10.⁵

Who is it for?

In Australia, apremilast is indicated for adults for the treatment of:^5,6

• moderate to severe plaque psoriasis, where the patient is a candidate for phototherapy or systemic therapy, and also
• signs and symptoms of active psoriatic arthritis, where there is an inadequate response to other anti-rheumatic medicines.

Australian guidance recommends that management for people with severe psoriasis include:^7,8

• phototherapy, and/or
• non-biologic systemic medicines, including:
  • methotrexate
  • apremilast
  • ciclosporin
  • acitretin

The PBS listing for apremilast for severe chronic plaque psoriasis is for people who have:¹

• failed to achieve an adequate response after at least 6 weeks of treatment with methotrexate OR
• a contraindication to methotrexate according to the Therapeutic Goods Administration (TGA) approved product information OR
• demonstrated severe intolerance of, or toxicity due to, methotrexate, AND
• experienced significant interference in their quality of life due to the condition.

People must not be receiving concurrent PBS-subsidised treatment for psoriasis with either a biological medicine or ciclosporin.¹

Dosing

Initiating apremilast involves taking a 10 mg oral tablet once in the morning on day one and gradually up-titrating to the continuing treatment dose of 30 mg twice a day, morning and evening, by day six. Treatment initiation should only be done by specialists experienced in the diagnosis and treatment of psoriasis.^5,6

Dose reduction is recommended for people with severe renal impairment (creatinine clearance [CrCl] <30 mL/minute). Treatment initiation involves only taking the morning doses and skipping the evening doses. The continuing treatment dose from day six is 30 mg once a day in the morning.^5,6

The medicine is provided as a:^1,9

• titration treatment pack for two weeks: 4 x 10 mg, 4 x 20 mg, 5 x 30 mg tablets for the first week; 14 x 30 mg tablets for the second week (PBS item number 12218C), or
• continuing treatment pack for four weeks: 56 x 30 mg tablets (PBS item number 12223H).

GPs and continuing treatment

At the May 2022 PBAC Meeting, the PBAC noted the claim of the sponsor (Amgen Australia Pty Ltd) that apremilast is well suited for GPs to prescribe continuing treatment for the following reasons:²

• it as an oral treatment and as a result, administration is not complicated.
• mild to moderate adverse events occur early in the treatment course and tend to self-resolve.
• unlike other psoriasis treatments, there are no monitoring requirements for apremilast.

The following safety issues are the most relevant to the continuation phase of treatment with apremilast.

Diarrhoea and nausea

Diarrhoea and nausea affect around 16% and 14% respectively of patients taking apremilast for psoriasis or psoriatic arthritis.⁶ People aged ≥ 65 years and people taking medicines that can lead to volume depletion or hypotension may be at a higher risk of these adverse effects. The effects are usually mild-to-moderate in severity. Most cases occur in the first 2 weeks and are resolved within 4 weeks, though some are prolonged for months. Dose reduction or discontinuation generally leads to quick improvement.^5,6

Weight loss

Pooled analysis of key clinical phase 3 trials has reported that around one in five people (21.9%) taking apremilast for 3 or more years lost > 5% of their baseline body weight, primarily during the first year of treatment.¹⁰

Patients prescribed apremilast should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, it should be evaluated and discontinuation of apremilast should be considered.⁶

Depression

In the same pooled analysis, patient-reported depression occurred in 1.4% of the treatment group versus 0.5% of people receiving placebo.¹⁰

People treated with apremilast, their caregivers and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes, and if such changes occur to contact their healthcare provider. Prescribers should carefully evaluate the risks and benefits of continuing treatment with apremilast if such events occur.⁶

Prescribers and pharmacists should discuss the following with people taking apremilast:

• Swallow the tablets whole with or without food⁹
• Do not crush, split or chew the tablets⁹
• Take the tablets with food to help if they have nausea¹⁰
• Be careful driving or using machines until they know how the medicine affects them.⁹

People taking apremilast should speak with their doctor or pharmacist if any of the following occur after taking the medicine:⁹

• they have nausea, vomiting or very bad diarrhoea,
• they lose weight for no clear reason or lose a large amount of weight,
• they start feeling depressed or have other mood changes, 
• their depression gets worse or they have thoughts about killing themselves.

• NPS MedicineWise bDMARDs program: Plaque psoriasis
• Australasian College of Dermatologists: Treatment goals for psoriasis