Certolizumab pegol binds to human TNFα with a KD of 90pM. TNFα is a key proinflammatory cytokine with a central role in inflammatory processes. Certolizumab pegol selectively neutralizes TNFα (IC90 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. (See Full Prescribing Information.)

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 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.

CIMZIA is administered by subcutaneous injection. The recommended initial dose of CIMZIA is 400 mg (given as two subcutaneous injections of 200 mg). Crohn's Disease: 400 mg initially and at Weeks 2 and 4. If response occurs, follow with 400 mg every four weeks. Rheumatoid Arthritis: 400 mg initially and at Weeks 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered. Psoriatic Arthritis: 400 mg initially and at week 2 and 4, followed by 200 mg every other week; for maintenance dosing, 400 mg every 4 weeks can be considered. Ankylosing Spondylitis: 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks. Non-radiographic Axial Spondyloarthritis: 400 mg (given as 2 subcutaneous injections of 200 mg each) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks. (See Full Prescribing Information.)

The most serious adverse reactions were: Serious Infections, Malignancies, Heart Failure, Hypersensitivity Reactions, Hepatitis B Virus Reactivation, Neurologic Reactions, Hematologic reactions, Autoimmunity, Immunosuppression. (See Full Prescribing Information.)

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.

Patients treated with CIMZIA are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease. Treatment with CIMZIA should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g. corticosteroids or methotrexate) may be at a greater risk of infection. (See Full Prescribing Information.)