Introduction
Certolizumab pegol (Cimzia) is a pegylated, humanized antigen-binding fragment (Fab') of a monoclonal antibody that specifically targets tumor necrosis factor-alpha (TNF-α). It is a biologic disease-modifying antirheumatic drug (bDMARD) approved for the treatment of several chronic inflammatory conditions. Unlike other TNF inhibitors, Cimzia lacks an Fc region, which may contribute to its unique pharmacokinetic and safety profile.
Mechanism of Action
Cimzia exerts its therapeutic effects by selectively binding to and neutralizing both soluble and membrane-bound human TNF-α. TNF-α is a proinflammatory cytokine that plays a central role in the pathogenesis of several inflammatory diseases. By inhibiting TNF-α, Cimzia reduces the inflammatory cascade, decreasing the production of other inflammatory mediators including interleukin-1 (IL-1), interleukin-6 (IL-6), and adhesion molecules. The pegylation of the Fab' fragment extends its half-life compared to non-pegylated Fab' fragments.
Indications
Cimzia is FDA-approved for:
- Moderate to severe rheumatoid arthritis (as monotherapy or in combination with methotrexate)
- Psoriatic arthritis
- Ankylosing spondylitis
- Moderate to severe Crohn's disease
- Plaque psoriasis
Dosage and Administration
Initial dosing:- Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 400 mg subcutaneously at weeks 0, 2, and 4
- Crohn's disease: 400 mg subcutaneously at weeks 0, 2, and 4
- Plaque psoriasis: 400 mg subcutaneously every other week (may initiate with 400 mg at weeks 0, 2, and 4)
- 200 mg subcutaneously every other week OR
- 400 mg subcutaneously every 4 weeks
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No specific recommendations
- Elderly: No dosage adjustment necessary
- Pregnancy: FDA Pregnancy Category B
Pharmacokinetics
Absorption: Bioavailability approximately 80% following subcutaneous administration Distribution: Volume of distribution is 6-8 L; limited tissue distribution due to pegylation Metabolism: Undergoes proteolytic degradation throughout the body Elimination: Half-life approximately 14 days; clearance approximately 0.4 L/day Special considerations: No Fc region, so does not undergo Fc-mediated clearance pathwaysContraindications
- History of hypersensitivity to certolizumab pegol or any component of the formulation
- Active tuberculosis or other active infections
- Patients with sepsis or risk of sepsis
Warnings and Precautions
Serious infections: Increased risk of bacterial, fungal, viral, and opportunistic infections Malignancy: Lymphoma and other malignancies have been reported Hepatotoxicity: Severe hepatic reactions, including acute liver failure Heart failure: Worsening or new-onset heart failure may occur Hematologic effects: Pancytopenia, including aplastic anemia Hypersensitivity reactions: Anaphylaxis and angioedema possible Neurologic events: Demyelinating disorders may occur Autoimmunity: Lupus-like syndrome and autoantibody formationDrug Interactions
Live vaccines: Avoid concurrent administration Anakinra: Increased risk of serious infections (avoid combination) Other TNF blockers: Increased risk of adverse effects (not recommended) Abatacept: Increased risk of serious infections (avoid combination) CYP450 substrates: May affect metabolism of drugs metabolized by CYP450 enzymesAdverse Effects
Most common (>10%): Upper respiratory infections, rash, urinary tract infections Common (1-10%): Hypertension, headache, injection site reactions, fever, nausea Serious (<1%):- Serious infections (tuberculosis, invasive fungal infections)
- Malignancies (lymphoma, skin cancer)
- Congestive heart failure
- Hepatotoxicity
- Blood dyscrasias
- Neurologic events
- Hypersensitivity reactions
Monitoring Parameters
Baseline:- TB screening (PPD or interferon-gamma release assay)
- Hepatitis B and C serology
- Complete blood count
- Liver function tests
- Renal function
- Pregnancy test if appropriate
- Signs and symptoms of infection
- Skin examination for malignancies
- CBC and LFTs periodically
- Clinical response assessment
- Injection site reactions
- Cardiac status in patients with heart failure
- Neurologic symptoms in patients with pre-existing demyelinating disorders
Patient Education
Administration:- Proper subcutaneous injection technique
- Rotation of injection sites
- Storage requirements (refrigerate at 2-8°C)
- Report any signs of infection (fever, cough, unusual fatigue)
- Avoid live vaccines during treatment
- Contact healthcare provider before dental procedures
- Regular follow-up appointments essential
- Report any new symptoms promptly
- Skin examinations for new or changing lesions
- Inform all healthcare providers about Cimzia therapy
- Use reliable contraception during treatment
- Report planned pregnancy to healthcare provider
References
1. FDA Prescribing Information: Cimzia (certolizumab pegol). 2023 2. Smolen JS, et al. Ann Rheum Dis. 2018;77(6):797-804 3. Schreiber S, et al. Gastroenterology. 2017;152(5):1105-1114 4. Mease PJ, et al. Arthritis Rheumatol. 2020;72(7):1107-1117 5. Reich K, et al. Br J Dermatol. 2017;176(6):1557-1568 6. Winthrop KL, et al. Clin Infect Dis. 2019;68(6):937-943 7. Mariette X, et al. Ann Rheum Dis. 2021;80(3):339-348 8. Product Monograph: Cimzia (certolizumab pegol). UCB Canada Inc. 2023
Note: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical advice.