Introduction
Certolizumab pegol is a pegylated, humanized antigen-binding fragment (Fab') of a monoclonal antibody that specifically targets human tumor necrosis factor-alpha (TNF-α). It is a biologic disease-modifying antirheumatic drug (bDMARD) used in the management of several chronic inflammatory conditions. Unlike other TNF inhibitors, certolizumab lacks an Fc region, which results in distinct pharmacokinetic properties and potentially different safety profiles.
Mechanism of Action
Certolizumab pegol selectively binds to and neutralizes both soluble and membrane-bound human TNF-α, a proinflammatory cytokine that plays a central role in inflammatory processes. By preventing TNF-α from interacting with its receptors (TNFR1 and TNFR2), certolizumab inhibits TNF-α-mediated cellular responses, including:
- Reduction of inflammatory cytokine production (IL-1, IL-6)
- Decreased adhesion molecule expression
- Attenuation of neutrophil activation and migration
- Inhibition of matrix metalloproteinase production
The pegylation of the Fab' fragment extends its half-life while the absence of an Fc region prevents complement activation and antibody-dependent cellular cytotoxicity.
Indications
FDA-approved indications include:
- Moderate to severe rheumatoid arthritis (as monotherapy or in combination with methotrexate)
- Psoriatic arthritis
- Ankylosing spondylitis
- Moderate to severe Crohn's disease
- Moderate to severe 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 every other week OR 400 mg every 4 weeks
- For Crohn's disease: 400 mg every 4 weeks
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: Use with caution; no specific dosage adjustment
- Pregnancy: Category B; may be used if clinically indicated
Pharmacokinetics
Absorption: Bioavailability approximately 80% following subcutaneous administration. Peak serum concentrations reached in 54-171 hours. Distribution: Volume of distribution is 6-8 L. Does not cross the blood-brain barrier effectively. Metabolism: Undergoes proteolytic catabolism to peptides and amino acids. Pegylation slows metabolic clearance. Elimination: Half-life approximately 14 days. Clearance primarily through proteolytic pathways. No significant renal or hepatic elimination.Contraindications
- Active tuberculosis or other serious infections
- History of hypersensitivity to certolizumab pegol or any component
- Patients with sepsis or risk of sepsis
- Moderate to severe heart failure (NYHA Class III/IV)
Warnings and Precautions
Serious infections: Increased risk of bacterial, viral, fungal, and opportunistic infections, including tuberculosis. Evaluate patients for latent TB before initiation. Malignancy: Increased risk of lymphoma and other malignancies, particularly in children and adolescents. Hepatotoxicity: Rare cases of severe hepatic reactions, including acute liver failure. Hematologic effects: Pancytopenia, including aplastic anemia, has been reported. Heart failure: Worsening or new-onset heart failure may occur. Hypersensitivity reactions: Anaphylaxis and angioedema possible. Autoimmunity: May develop autoantibodies and lupus-like syndrome.Drug Interactions
Live vaccines: Avoid concurrent administration (increased risk of infection) Anakinra: Increased risk of serious infections (avoid combination) Other TNF blockers: Increased risk of adverse effects (not recommended) CYP450 substrates: Certolizumab may affect formation of CYP450 enzymes during chronic inflammationAdverse Effects
Most common (>10%): Upper respiratory tract infections, rash, urinary tract infections Common (1-10%):- Infections: Herpes, pharyngitis
- Gastrointestinal: Abdominal pain, nausea
- Neurological: Headache, dizziness
- Injection site reactions: Erythema, pain, swelling
- Laboratory abnormalities: Increased liver enzymes
- Serious infections (sepsis, tuberculosis, invasive fungal infections)
- Malignancies (lymphoma, skin cancer)
- Congestive heart failure
- Demyelinating disorders
- Hematologic toxicity
- Severe hypersensitivity reactions
Monitoring Parameters
Before initiation:- Tuberculosis screening (PPD or interferon-gamma release assay)
- Hepatitis B and C serology
- Complete blood count
- Liver function tests
- Renal function assessment
- Cardiovascular assessment
- Signs and symptoms of infection (at every visit)
- CBC and liver function tests periodically (every 3-6 months)
- Skin examination for malignancy
- Disease activity assessment
- Injection site reactions
- Patient-reported outcomes
- Annual tuberculosis screening
- Regular malignancy screening appropriate for age and risk factors
- Cardiovascular risk assessment
Patient Education
- Report any signs of infection (fever, cough, flu-like symptoms) immediately
- Understand proper injection technique if self-administering
- Avoid live vaccines during therapy
- Inform all healthcare providers about certolizumab use
- Report any new neurological symptoms
- Monitor for skin changes or unusual lesions
- Understand the increased malignancy risk
- Report any symptoms of heart failure (shortness of breath, swelling)
- Notify provider if pregnancy is planned or suspected
- Keep all scheduled follow-up appointments
References
1. FDA Prescribing Information: Cimzia (certolizumab pegol) 2. Smolen JS, et al. Ann Rheum Dis. 2020;79(6):685-699 3. Schreiber S, et al. N Engl J Med. 2017;377(10):954-965 4. Mease PJ, et al. Arthritis Rheumatol. 2020;72(1):23-37 5. Reich K, et al. J Am Acad Dermatol. 2021;84(4):1023-1033 6. van der Heijde D, et al. Arthritis Res Ther. 2019;21(1):281 7. American College of Rheumatology Guidelines for Rheumatoid Arthritis Treatment, 2021 8. Crohn's and Colitis Foundation Treatment Guidelines, 2020