Approved April 22, 2008

CERTOLIZUMAB PEGOL
(FDA Category 1)

CIMZIA(R) (UCB, Inc) is a tumor necrosis factor inhibitor, which results in an interference in the production of downstream inflammatory mediators, including interleukin1, prostaglandins, platelet activating factor, and nitric oxide. It is a recombinant, humanized antibody Fab' fragment conjugated with polyethylene glycol polymer and manufactured in E. Coli.

DOSING INFORMATION: The recommended initial dose is 400 milligrams (mg) subcutaneously (subQ) (as two subQ injections of 200 mg) once and then repeat at weeks 2 and 4. If a clinical response is achieved, the maintenance dose is 400 mg subQ once every 4 weeks.

PHARMACOKINETICS: Following subcutaneous (subQ) administration of certolizumab pegol, the peak plasma concentrations were reached in 54 to 171 hours. The bioavailability following subQ administration was approximately 80% (range 76% to 88%) compared with intravenous administration. For a fixed dose of certolizumab pegol, the steady state concentration (Css) ranged from 0.5 to 90 mcg/mL, and in patients with anti-certolizumab pegol antibodies, the Css was 0.5 to 75 mcg/mL. The terminal elimination phase half-life was approximately 14 days for all doses tested (subQ dosing).

CAUTIONS: Serious infections, including tuberculosis and invasive fungal infections, and sepsis (some fatal cases) have been reported with certolizumab pegol therapy. Medically-significant cytopenias, malignancies, hypersensitivity reactions, and demyelinating disease have been reported infrequently with the use of certolizumab pegol. Caution is warranted in patients with ongoing, or a history of, significant hematologic abnormalities. Cardiac failure, arrhythmia, pericardial effusion, and myocardial infarction have been observed with certolizumab pegol treatment during controlled or uncontrolled clinical studies. Common side effects include infection (urinary tract, upper respiratory) and arthralgia. Concomitant use with anakinra or live vaccines is not recommended.

FDA APPROVED INDICATIONS: Certolizumab pegol is approved for maintaining clinical response and reducing signs and symptoms of moderate to severe Crohn's disease in adults who had inadequate response to conventional therapy.