Certolizumab Pegol

Abstract

Certolizumab pegol (Cimzia(®)) is a recombinant, polyethylene glycolylated, antigen-binding fragment of a humanized monoclonal antibody that selectively targets and neutralizes tumour necrosis factor (TNF)-α. The drug is indicated for subcutaneous use every 2 or 4 weeks (q2w or q4w) for the treatment of adults with moderate to severe active rheumatoid arthritis (RA). The efficacy of subcutaneous certolizumab pegol in adults with active RA has been investigated in several well designed, placebo-controlled trials. In four pivotal studies of ≤52 weeks duration, patients with moderate to severe disease receiving recommended dosages of certolizumab pegol (200 mg q2w or 400 mg q4w), either as monotherapy (after failing prior disease-modifying anti-rheumatic drug [DMARD] therapy) or in combination with methotrexate (after responding inadequately to methotrexate alone), experienced rapid clinical improvement, with some combination trials also demonstrating inhibition of radiographic progression. The beneficial effects of certolizumab pegol therapy were generally maintained for up to ≈5 years in clinical trial extensions in which the drug was administered at dosages of 400 mg q4w or q2w. Additional studies suggest certolizumab pegol is also effective in patients who are Asian or have low to moderate disease activity, as well as more clinically representative patient populations. The tolerability profile of certolizumab pegol was acceptable, with infections/infestations the most common adverse events. Thus, certolizumab pegol is an effective option for the management of active RA in adults, although additional long-term and comparative efficacy and tolerability data are needed to help definitively position certolizumab pegol relative to other biological DMARDs, particularly other anti-TNF agents.

Certolizumab-Induced Uveitis: A Case Report and Review of the Literature

“…It is a recombinant, polyethylene glycolylated, antigen-binding fragment of a humanized monoclonal antibody that selectively targets and neutralizes TNFα [5]. Infliximab and adalimumab are monoclonal antibodies directed toward TNFα, and etanercept is a TNF-receptor-fusion protein conjugated to the Fc portion of human IgG.…”

“…Induced sarcoidosis has been reported in association with infliximab, etanercept and adalimumab [1, 2, 4]. Certolizumab is a new TNFα antagonist which has been proven to be effective in the treatment of RA [5]. A review of the literature revealed no previous occurrence of sarcoidosis induced by this agent.…”

Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis

“…Three of the most successful are monoclonal antibodies targeting TNF α directly and blocking its binding to TNFRII: infliximab or remicade [ 2 ], adalimumab or Humira [ 3 ], and golimumab or Simponi [ 4 ]. Currently approved therapeutics also include an antibody Fab′ fragment conjugated to a polyethylene glycol (PEG) (certolizumab pegol or Cimzia) [ 5 – 7 ] and a fifth biologic, etanercept or Enbrel, which comprises of a fusion protein of TNFRII and the Fc region of human IgG1 [ 8 ]. Although targeting TNF α has been validated through proven therapeutic efficacy (and significant commercial value), not all patients respond with 25–40% of subjects failing to reach the desired ACR20 end point (20% improved response based on the American College of Rheumatology) during clinical trials [ 9 – 11 ].…”

Efficacy of anti–tumor necrosis factor therapy for extra-articular manifestations in patients with ankylosing spondylitis: a meta–analysis

“…Infliximab (INF) is a chimeric mouse–human monoclonal immunoglobulin G (IgG) 1 antibody [ 17 ]. Adalimumab (ADA) [ 18 ], golimumab (GOL) [ 18 ] and certolizumab (CZP) [ 19 ] are humanized monoclonal anti-TNF-α antibodies. Etanercept (ETA) [ 20 ] is a dimeric fusion protein of the TNF receptor linked to the Fc portion of human IgG1.…”