CIMZIA

What it is

Cimzia is a 200 mg/mL injection containing certolizumab pegol. Certolizumab pegol is a recombinant, humanised antibody Fab' fragment that is expressed in an Escherichia coli bacterial expression system, subsequently purified and conjugated to polyethylene glycol (PEG). Cimzia injection is available as a sterile clear to opalescent solution that is colourless to yellow, in a single-use pre-filled syringe or pre-filled pen (AutoClicks®).

Approved indications

— Moderate to severe active rheumatoid arthritis in adult patients, combined with MTX in case of either an inadequate response or intolerance to previous therapy with one or more disease modifying antirheumatic drugs (DMARDs), or as monotherapy in case of a contraindication or intolerance to MTX. — Severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX or other DMARDs, in combination with MTX. — Active psoriatic arthritis in adult patients where response to previous disease modifying antirheumatic drug therapy (DMARDs) has been inadequate. — Active ankylosing spondylitis in adult patients who have been intolerant to or have had inadequate response to at least one nonsteroidal anti-inflammatory drug (NSAID). — Active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation as indicated by elevated C reactive protein (CRP) and/or magnetic resonance imaging (MRI) change, in adults who have had an inadequate response to, or are intolerant to, nonsteroidal anti-inflammatory drugs (NSAIDs). — Moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Dosing overview

The recommended loading dose of Cimzia for adult patients is 400 mg (given as 2 subcutaneous injections of 200 mg each) initially (Week 0) and at Weeks 2 and 4. For rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis, clinical response is usually achieved within 12 weeks of treatment, and continuation of therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 12 weeks. For plaque psoriasis, continuation of therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within the first 16 weeks, although in some patients clinical response is only achieved after 16 weeks of treatment.

Key safety warnings

TNF mediates inflammation and modulates cellular immune responses, so TNF blocking agents including Cimzia may affect host defences against infections and malignancies. Patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis may not manifest typical symptoms of infection, including fever, so early detection of any infection is critical to minimise delays in diagnosis and initiation of treatment. Patients must be monitored closely for signs and symptoms of infections including tuberculosis before, during and after treatment with Cimzia, taking into account the 14 day half-life of the product. Because the elimination of certolizumab pegol may take up to 5 months, monitoring should be considered throughout this period. Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating Cimzia, with tuberculin skin test and chest X-ray performed in all patients. Reactivation of hepatitis B occurred in patients receiving TNF-antagonists including Cimzia who are chronic carriers of this virus (surface antigen positive), and in some instances, HBV reactivation occurring in conjunction with TNF-antagonist therapy has been fatal. In clinical studies with Cimzia and other TNF-antagonist agents, more cases of lymphoma and other malignancies have been observed among patients receiving TNF-antagonists than in control patients receiving placebo, although the occurrence was uncommon or rare, and a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be excluded. Melanoma and Merkell cell carcinoma have been reported in patients treated with TNF-antagonists including Cimzia, and periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer. Cimzia should be used with caution in patients with mild heart failure (NYHA class I/II) and is contraindicated in moderate or severe heart failure. Use of TNF-antagonists has been associated with rare cases of exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease including multiple sclerosis, and peripheral demyelinating disease including Guillain-Barré syndrome, so prescribers should exercise caution in considering the use of Cimzia in patients with pre-existing or recent onset central nervous system demyelinating disorders.

Contraindications

Hypersensitivity to the active substance or to any of the excipients. Active tuberculosis or other severe infections such as sepsis or opportunistic infections. Concurrent administration of Cimzia and anakinra (an interleukin-1 receptor antagonist). Moderate to severe heart failure (NYHA classes III/IV).

PBS listing

Cimzia 200 mg in 1 mL is listed on the PBS in two formulations: single-use pre-filled syringe and pre-filled pen solution for injection. Each formulation has 13 PBS items with authority required and streamlined restrictions. The ex-manufacturer price is A$938.04.

Regulatory history

Cimzia certolizumab pegol 200 mg/mL solution for injection in pre-filled syringe was first listed on the ARTG on 20 January 2010. The pre-filled pen formulation was first listed on the ARTG on 10 February 2017. In November 2014, the PBAC recommended amendments to allow treatment of patients with severe active rheumatoid arthritis, severe active ankylosing spondylitis, and severe active psoriatic arthritis who had failed prior treatment with an anti-TNF-α agent other than certolizumab pegol. In November 2017, the PBAC recommended an amendment to allow certolizumab pegol to be used as a first-line biological disease-modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis. In March 2019, the PBAC recommended an Authority Required listing for severe chronic plaque psoriasis on a cost-minimisation basis. In November 2019, the PBAC recommended an Authority Required listing for non-radiographic axial spondyloarthritis, cost-minimised to golimumab. An AusPAR was published on 29 May 2019 approving Certolizumab pegol (Cimzia) for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.