certolizumab

Certolizumab pegol is a biologic disease-modifying antirheumatic drug (bDMARD) that works by binding soluble and membrane-bound TNF-α, preventing it from interacting with its receptors (TNFR1/TNFR2) on cell surfaces. This blocks downstream pro-inflammatory signaling (NF-κB activation), reducing inflammation, cytokine release, and immune cell recruitment characteristic of autoimmune diseases.

Structurally, certolizumab differs from other TNF inhibitors (infliximab, adalimumab, etanercept, golimumab) in that it consists only of a PEGylated Fab' fragment without the Fc portion of the antibody. This confers several unique properties: it does not fix complement or cause antibody-dependent cellular cytotoxicity (ADCC), has a prolonged half-life due to PEGylation, and does not cross the placenta efficiently in the first two trimesters (very low transfer), making it the anti-TNF agent of choice for pregnant patients with autoimmune disease requiring biologic therapy.

Clinical uses include rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Key adverse effects and considerations, shared with other anti-TNF biologics, include: - Increased risk of infections, particularly reactivation of latent tuberculosis (screen with PPD/IGRA before starting) and reactivation of hepatitis B. - Increased risk of certain malignancies, notably lymphoma (rare) and non-melanoma skin cancers. - Risk of drug-induced lupus-like syndrome. - Injection site reactions. - Worsening of heart failure (contraindicated in moderate-severe CHF, similar class warning to other TNF inhibitors). - Should not be given with live vaccines.

Mechanism-related boards pearls: TNF-α is central to granuloma formation, so anti-TNF therapy increases risk of reactivation TB and other granulomatous infections (histoplasmosis). Screening for latent TB and hepatitis B is mandatory before initiation.