Certolizumab pegol

CIMZIA is a tumor necrosis factor (TNF) blocker indicated for: Reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. Treatment of adults with moderately to severely active rheumatoid arthritis. Treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older. Treatment of adult patients with active psoriatic arthritis. Treatment of adults with active ankylosing spondylitis. Treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation. Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

Certolizumab pegol binds to human TNFα with a KD of 90pM. TNFα is a key pro-inflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFα (IC 90 of 4 ng/mL for inhibition of human TNFα in the in vitro L929 murine fibrosarcoma cytotoxicity assay) but does not neutralize lymphotoxin α (TNFβ). Certolizumab pegol cross-reacts poorly with TNF from rodents and rabbits, therefore in vivo efficacy was evaluated using animal models in which human TNFα was the physiologically active molecule. Certolizumab pegol was shown to neutralize membrane-associated and soluble human TNFα in a dose-dependent manner. Incubation of monocytes with certolizumab pegol resulted in a dose-dependent inhibition of LPS-induced TNFα and IL-1β production in human monocytes.

CIMZIA is administered by subcutaneous injection. Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard. When a 400 mg dose is needed (given as two subcutaneous injections of 200 mg), injections should occur at separate sites in the thigh or abdomen. The solution should be carefully inspected visually for particulate matter and discoloration prior to administration. The solution should be a clear to opalescent, colorless to yellow liquid, essentially free from particulates and should not be used if cloudy or if foreign particulate matter is present. CIMZIA does not contain preservatives, therefore, unused portions of drug remaining in the syringe or vial should be discarded. Crohn's Disease 400 mg initially and at Weeks 2 and 4.

CIMZIA is contraindicated in patients with a history of hypersensitivity reaction to certolizumab pegol or to any of the excipients. Reactions have included angioedema, anaphylaxis, serum sickness, and urticaria. Serious hypersensitivity reaction to certolizumab pegol or to any of the excipients.

Boxed warning (serious infections and malignancy serious infections): Patients treated with CIMZIA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. CIMZIA should be discontinued if a patient develops a serious infection or sepsis. Serious Infections: CIMZIA should not be initiated in patients with an active infection. Monitor for infection during and after treatment, discontinue if a serious infection develops. If invasive fungal infection develops in patients who reside or travel to regions where mycoses are endemic, consider empiric antifungal therapy. Malignancies: Cases of lymphoma and other malignancies have been observed among patients receiving TNF blockers, including CIMZIA.

The most serious adverse reactions were: Serious Infections Malignancies Heart Failure Hypersensitivity Reactions Hepatitis B Virus Reactivation Neurologic Reactions Hematologic Reactions Autoimmunity Immunosuppression Most common adverse reactions (≥7%): upper respiratory tract infection, rash, and urinary tract infection

Laboratory Tests: May cause erroneously elevated aPTT results. Use with Anakinra, Abatacept, Rituximab, and Natalizumab An increased risk of serious infections has been seen in clinical studies of other TNF-blocking agents used in combination with anakinra or abatacept, with no added benefit. Formal drug interaction studies have not been performed with rituximab or natalizumab. Because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of CIMZIA in these combinations. There is not enough information to assess the safety and efficacy of such combination therapy. Therefore, the use of CIMZIA in combination with anakinra, abatacept, rituximab, or natalizumab is not recommended.

Refrigerate CIMZIA vials and prefilled syringes between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Unopened CIMZIA lyophilized vials may also be stored at room temperature up to a maximum of 25°C (77°F) for 6 months, but not exceeding the original expiration date. If stored at room temperature, do not place back in refrigerator and write the new expiration date on the carton in the space provided. Do not shake.