ENBREL

What it is

ENBREL contains etanercept as its active ingredient. ENBREL is available as a powder for injection containing 25 mg of etanercept per vial, and as a solution for injection in pre-filled syringes (25 mg in 0.5 mL or 50 mg in 1 mL), dose-dispenser cartridges (25 mg in 0.5 mL or 50 mg in 1 mL), and an auto-injector (50 mg).

Approved indications

**Adults** — Active rheumatoid arthritis in patients who have had inadequate response to one or more disease-modifying antirheumatic drugs. — Severe, active rheumatoid arthritis in adults to slow progression of disease-associated structural damage in patients at high risk of erosive disease. — Active and progressive psoriatic arthritis in adults when the response to previous disease-modifying antirheumatic therapy has been inadequate; ENBREL has been shown to reduce the rate of progression of joint damage and to improve physical function. — Moderate to severe chronic plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy. — Active ankylosing spondylitis in adults. — Active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein and/or MRI change who have had an inadequate response to NSAIDs, defined as a Bath Ankylosing Spondylitis Disease Activity Index score of ≥ 4. **Children and adolescents** — Active polyarthritis (rheumatoid factor positive or negative) in children and adolescents, aged 2 to 17 years, who have had an inadequate response to one or more DMARDs. — Active extended oligoarthritis in children and adolescents, aged 2 to 17 years, who have had an inadequate response to, or who have proved intolerant to, methotrexate. — Active enthesitis-related arthritis in adolescents, aged 12 to 17 years, who have had an inadequate response to, or who have proved intolerant to, conventional therapy. — Active psoriatic arthritis in adolescents, aged 12 to 17 years, who have had an inadequate response to, or who have proved intolerant to, methotrexate. — Chronic, severe plaque psoriasis in children and adolescents from 4 to 17 years, who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies; treatment is limited to no longer than 24 weeks and should be ceased after 12 weeks if a significant PASI response is not achieved.

Dosing overview

**Adults** For rheumatoid arthritis, psoriatic arthritis, non-radiographic axial spondyloarthritis and ankylosing spondylitis, the recommended dose of ENBREL is 50 mg per week, given as a subcutaneous injection, either once weekly as a single 50 mg injection or twice weekly as two separate 25 mg injections given 3–4 days apart. For plaque psoriasis, the recommended dose is 50 mg per week, given once weekly or twice weekly as a subcutaneous injection; higher responses may be achieved from initial treatment for up to 12 weeks with a dose of 50 mg given twice weekly, after which the dose should be reduced to the standard dose of 50 mg per week; treatment should be discontinued in patients who do not show a significant PASI response after 12 weeks. **Children and adolescents** For juvenile idiopathic arthritis in children 2–17 years of age, the recommended dose is 0.8 mg/kg (up to a maximum of 50 mg per dose) given once weekly as a subcutaneous injection, or 0.4 mg/kg (up to a maximum of 25 mg), given twice weekly with an interval of 3–4 days between doses. For paediatric plaque psoriasis in children 4 years and above, the recommended dose is 0.8 mg/kg (up to a maximum of 50 mg per dose), given once weekly as a subcutaneous injection for up to 24 weeks; treatment should be discontinued in patients who do not show a significant PASI response after 12 weeks.

Key safety warnings

**Infections** Serious infections including sepsis and tuberculosis, some of which have been fatal, have been reported with the use of ENBREL. These infections were due to bacteria, mycobacteria, fungi, viruses and parasites; opportunistic infections have also been reported, including listeriosis, legionellosis and invasive fungal infections. Administration of ENBREL should be discontinued if a patient develops a serious infection such as tuberculosis or an atypical mycobacterial infection, or sepsis. **Tuberculosis** Tuberculosis, including disseminated or extrapulmonary presentation, has been observed in patients receiving ENBREL; tuberculosis may be due to reactivation of latent infection or to new infection. Before initiation of therapy with ENBREL, any patient at increased risk for TB should be evaluated for active or latent infection; if active TB is diagnosed, ENBREL therapy must not be initiated; prophylaxis of latent TB infection should be initiated prior to therapy with ENBREL. **Hepatitis B reactivation** Reactivation of hepatitis B in patients who were previously infected with the hepatitis B virus and had received ENBREL has been reported; in some instances, HBV reactivation occurring in conjunction with ENBREL therapy has been fatal. Patients who were previously infected with HBV and require treatment with ENBREL should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. **Neurological disorders** Treatment with ENBREL has been associated with rare cases of new onset or exacerbation of central nervous system demyelinating disorders, some presenting with mental status changes and some associated with permanent disability; cases of transverse myelitis, optic neuritis, multiple sclerosis, and new onset or exacerbation of seizure disorders have been observed. **Congestive heart failure** There have been post-marketing reports of worsening of congestive heart failure, with and without identifiable precipitating factors, in patients taking ENBREL; there have also been rare reports of new onset congestive heart failure, including in patients without known pre-existing cardiovascular disease. **Malignancy risk** In the controlled portions of clinical trials of TNF blocking agents, more cases of lymphoma have been observed among patients receiving the TNF blocker compared to control patients; during the controlled portions of ENBREL trials, 3 lymphomas were observed among 4,509 ENBREL-treated patients versus 0 among 2,040 control patients.

Contraindications

Known hypersensitivity to etanercept or to any of its excipients; patients with, or at risk of, sepsis; treatment with ENBREL should not be initiated in patients with serious, active infection including chronic or localised infections. Concurrent treatment with Interleukin-1 antagonists is contraindicated.

PBS listing

ENBREL 25 mg powder for injection is listed on the PBS as an injection set containing 4 vials and 4 pre-filled syringes, with 17 PBS items and a streamlined or authority-required restriction, at an ex-manufacturer price of A$371.81 (latest schedule 2026-05-01).

Regulatory history

ENBREL 25 mg powder for injection was first registered on the ARTG on 2003-03-18. Pre-filled syringe presentations (25 mg and 50 mg) were registered on 2007-03-06, followed by the 50 mg auto-injector on 2009-04-07 and the dose-dispenser cartridges (25 mg and 50 mg) on 2021-03-23. In November 2014, the PBAC recommended a change to the PBS listing for severe active rheumatoid arthritis to allow use in combination with methotrexate. In November 2017, the PBAC recommended an amendment to the PBS listing to allow ENBREL to be used as a first-line biological disease-modifying anti-rheumatic drug for rheumatoid arthritis. An AusPAR was issued on 2014-02-12 for the indication of Juvenile Idiopathic Arthritis.