Certolizumab pegol (CZP) is a humanized, recombinant Fab' fragment of a high affinity anti-tumor necrosis factor alpha (TNFa) monoclonal antibody that has been conjugated to polyethylene glycol (“PEGylated”) to prolong the compound’s elimination half-life. CZP targets both the soluble and membrane-bound forms of TNFα. Due to the absence of the Fc portion of the antibody, in vitro studies show that CZP does not fix complement, trigger antibody-dependent cell-mediated toxicity, induce neutrophil degranulation, or induce apoptosis in human peripheral blood monocytes or lymphocytes.
CZP is self-administered as a subcutaneous injection and is available as a lyopholized powder and in 200mg/mL prefilled syringes.
In April 2008, CZP was approved in the United States for treatment of moderately to severely active Crohn’s disease in patients with an inadequate response to conventional therapy. Pre-licensing studies included the 'PRECISE 1' and 'PRECISE 2' trials: In the Precise 1 study, a “modest improvement” in response, but not remission, was reported. In the Precise 2 study, a continuation study for responders of the Precise 1 study, maintenance treatment with CZP resulted in an increased likelihood of remission at 26 weeks.
In May 2009, CZP was FDA-approved for treatment of moderately to severely active rheumatoid arthritis (RA). In clinical trials of patients with inadequate responses to DMARDs, including methotrexate, CZP as monotherapy (FAST4WARD) and CZP plus methotrexate (MTX) (RAPID 1 and 2) significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage.
In September 2013, CZP was FDA-approved for treatment of adult patients with active psoriatic arthritis (PsA). In patients with active and progressive adult-onset PsA, with or without prior anti-TNFa exposure, CZP improved clinical and radiographic disease progression, as measured by ACR20 score (RAPID-PsA study).
In October 2013, CZP was FDA-approved for treatment of adults with active ankylosing spondylitis (AS). Approval was based on data from a phase 3 study (RAPID-axSpA) of patients with active axial spondyloarthritis, the majority of which had AS. Improvement in signs and symptoms of AS, as measured by ASAS20 score, were seen at 12 weeks in patients receiving CZP compared with placebo.
The major safety concerns related to CZP use mirror those of other TNFa inhibitors, including increased risk of serious infection (e.g., tuberculosis, bacterial sepsis, invasive fungal and/or other opportunistic infections), increased risk of malignancy (e.g., lymphoma, skin cancer), and risk of Hepatitis B reactivation. As such, prior to initiating CZP therapy, testing for active/latent tuberculosis and Hepatitis B infection is recommended. In addition, periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer. Other reported adverse effects include hypertension, congestive heart failure, demyelinating disease, autoantibody formation and sarcoidosis.
CZP is not recommended for use with other biologics, including (but not limited to) abatacept, anakinra, natalizumab, rituximab and other TNFa inhibitors. In addition, live vaccines should be withheld during therapy with CZP. CZP is classified as Pregnancy Category B.