Certolizumab

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Crohn's Disease

Certolizumab pegol is a PEGylated tumor necrosis factor alpha (TNF-α) inhibitor used to treat various inflammatory autoimmune conditions. This biologic medication has a unique structure lacking an Fc region, which may provide certain advantages including reduced placental transfer during pregnancy.

Mechanism of Action

Certolizumab pegol consists of a humanized antibody Fab' fragment specific for TNF-α that is conjugated to polyethylene glycol (PEG). Unlike other TNF inhibitors, it lacks the Fc portion of a complete antibody. The Fab' fragment binds to and neutralizes human TNF-α, preventing it from binding to TNF receptors on cell surfaces. This blocks TNF-α's pro-inflammatory effects, including activation of immune cells, induction of cytokines, and promotion of joint destruction. The PEGylation extends the half-life, allowing less frequent dosing. The absence of the Fc region means certolizumab does not induce complement-mediated cytotoxicity or antibody-dependent cell-mediated cytotoxicity.

Available Formulations

Certolizumab pegol is available as a solution for subcutaneous injection in prefilled syringes (200 mg/mL) and as a lyophilized powder requiring reconstitution. The prefilled syringes are designed for self-administration after proper training. The medication requires refrigeration but should be brought to room temperature before injection.

Medical Uses

Certolizumab is FDA-approved for moderately to severely active rheumatoid arthritis (RA), active psoriatic arthritis (PsA), active ankylosing spondylitis (AS), moderate to severe plaque psoriasis, active non-radiographic axial spondyloarthritis with objective signs of inflammation, and moderately to severely active Crohn's disease (when conventional therapy has failed). It can be used alone or in combination with non-biologic DMARDs such as methotrexate.

Dosing Guidelines

For rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and axial spondyloarthritis, the recommended dose is 400 mg (two 200 mg injections) initially and at weeks 2 and 4, followed by 200 mg every other week or 400 mg every 4 weeks for maintenance. For plaque psoriasis, the loading dose is the same, with maintenance of 400 mg every other week. For Crohn's disease, the loading dose is followed by 400 mg every 4 weeks. If response is incomplete, consider maintenance of 400 mg every 4 weeks.

Important Safety Information

Certolizumab carries a boxed warning for serious infections (including tuberculosis, invasive fungal infections, and bacterial/viral infections) and malignancy (including lymphoma and other malignancies, some in children and adolescents). All patients should be tested for latent tuberculosis before starting therapy. The medication should not be initiated during active infections. Other serious risks include hepatitis B reactivation, heart failure worsening, demyelinating disease, hematologic reactions, and hypersensitivity reactions including anaphylaxis.

Drug Interactions

Certolizumab should not be used concurrently with other biologic DMARDs or TNF blockers (anakinra, abatacept, rituximab) due to increased infection risk. Live vaccines should be avoided during treatment. There are no significant pharmacokinetic interactions with methotrexate or other non-biologic DMARDs. Therapeutic drug monitoring may be considered in patients with inadequate response or suspected immunogenicity.

Special Populations

Unlike other TNF inhibitors, certolizumab has minimal to no placental transfer due to the absence of the Fc region. It is the only TNF inhibitor with pregnancy data suggesting no increased risk of birth defects and is often preferred if TNF inhibition is needed during pregnancy. Small amounts are present in breast milk; the benefits of breastfeeding should be considered. Safety and efficacy have not been established in pediatric patients. No dose adjustment is needed for elderly patients or those with renal impairment. Patients with hepatic impairment have not been specifically studied.