Certolizumab pegol (Cimzia)

Presently the only PEGylated anti-TNFα biologic approved for the treatment of rheumatoid arthritis and Crohn’s disease.

A humanized antigen-binding fragment (Fab’) of a monoclonal antibody that has been conjugated to polyethylene glycol.

A Fc-free, PEGylated, anti-TNFα monoclonal antibody.

Trade name Cimzia.

Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine implicated in the pathogenesis of rheumatoid arthritis (RA) and Crohn disease (CD), and TNFα is a key mediator of the inflammation-induced joint damage.

Reduction in TNFα levels improves signs and symptoms of RA.

Biologics with other modes of action that are marketed for the treatment of RA include abatacept (T cell signaling inhibitor), rituximab (B cell depleting, anti-CD20 antibody), anakinra (IL-1 receptor antagonist) and tocilizumab (anti-interleukin-6 receptor antibody).

For Crohn’s disease, certolizumab pegol, infliximab, adalimumab and natalizumab (an antibody that targets the cellular adhesion molecule α4-integrin) are approved therapeutics.

Inhibits joint damage and improvement in physical function in RA.

A disease-modifying antirheumatic drug (DMARD) for the treatment of moderate-to-severe RA.

Approved in combination with methotrexate (MTX) for patients where the response to DMARDs, including MTX, has been inadequate.

Can be initiated in case of intolerance to MTX or when continued treatment with MTX is inappropriate.

Recommended dosing regimen in RA is 400 mg certolizumab pegol administered subcutaneously at weeks 0, 2 and 4, followed by 200 mg every 2 weeks.

400 mg certolizumab pegol every 4 weeks can also be considered as a maintenance dose.

Approved for the reduction of signs and symptoms of CD and maintenance of a clinical response in adult patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy.

The dosing for CD is 400 mg certolizumab pegol subcutaneously at weeks 0, 2 and 4, followed by 400 mg every 4 weeks in patients who experienced a response.

Self-injection of the liquid formulation by the patient is possible if deemed appropriate by the physician.

Lacks an Fc region, which minimizes potential Fc-mediated effects such as complement-dependent cytotoxicity (CDC) or antibody dependent cell-mediated cytotoxicity (ADCC).

The lack of an Fc region may also be a factor in the prevention of transfer of it across the placenta during pregnancy.

It is classified in the US as pregnancy category B.

Differs from the other TNFα-inhibitors as it is PEGylated.

PEGylation significantly increases the circulating half-life of Fab’ molecules, permitting a minimum dosing interval of 2 weeks for certolizumab pegol.

Certolizumab pegol is effective in the reduction of signs and symptoms of active RA with 400 mg dose administered every 4 weeks.

The most common adverse events (AEs) are headache, nausea and infection.

Phase 3 studies with certolizumab pegol in combination with MTX: Overall, in the RAPID studies certolizumab pegol plus MTX demonstrated rapid and sustained reductions in the signs and symptoms of moderate-to-severe RA, inhibition of the progression of structural joint damage and improved physical functioning, when the response to MTX had previously been inadequate.

Serious infection are observed more frequently in the certolizumab pegol arms than in the placebo arm; in pooled RAPID 1 and 2 populations, serious infections occurred at the rate of 6.0 and 7.1 per 100 patient-years in the certolizumab pegol 200 mg and 400 mg plus MTX groups, respectively, compared to 1.5 per 100 patient-years in the placebo plus MTX group.

The most common serious infections are tuberculosis, pneumonia and erysipelas.

Phase 3 studies with certolizumab pegol monotherapy indicated treatment with certolizumab pegol 400 mg monotherapy every 4 weeks compared to placebo improved the signs and symptoms of active RA in patients who had previously failed at least one prior DMARD.

Adverse events reported 75% of certolizumab pegol-treated patients but the majority are mild or moderate in nature.

The induction and maintenance therapy with certolizumab pegol in patients with moderate-to-severe CD offers a modest improvement in response rates compared to placebo.

Certolizumab pegol has significant superior efficacy over placebo in the treatment of moderate-to-severe chronic plaque psoriasis.

Presently the only PEGylated anti-TNFα approved for the treatment of RA and CD.

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