Certolizumab pegol (CZP) is a polyethylene glycol (PEG)ylated Fc-free TNFi, which has been shown to be effective in the treatment of rheumatoid arthritis. FDA approval of CZP for active PsA in September 2013 was based on data from the RAPID-PsA study, a phase 3, multicentre, randomized, double-blind, placebo-controlled trial (randomized controlled trial, RCT) designed to evaluate the efficacy and safety of CZP in 409 patients with active and progressive adult onset PsA, which have previously failed at least one disease-modifying antirheumatic drug (DMARD).[7,11,12] Twenty percent of patients included had received a prior TNFi. Patients received a loading dose of certolizumab pegol 400 mg at weeks 0, 2 and 4 or placebo, followed by CZP 200 mg every other week (eow), CZP 400 mg every 4 weeks (q4w) or placebo every other week. At week 12, ACR20 response was significantly greater in CZP patients (58% CZP 200 eow, 52% CZP 400 q4w and 24% placebo), with improvements observed by week 1. Improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease[7,13–18] (Table 1 ). At week 24, 62.2 and 60.5% of patients were treated with CZP 200 mg q2w and CZP 400 mg q4w, respectively, and achieved a PASI75 response, compared with 15.1% in the placebo group (P < 0.001). Patients with a prior TNFi exposure responded in a similar way at weeks 12 and 24 to patients failing a traditional DMARD. In another recent report, low radiographic progression (0.0 at week 24, 0.13 at week 48) was maintained in the CZP arms.
Certolizumab pegol is a novel TNF inhibitor, consisting of a humanized Fab fragment (50 kDa) fused to a 40-kDa PEG moiety. This unique structure may avoid potential Fc-mediated effects seen in vitro, such as complement-dependent or antibody-dependent cell-mediated cytotoxicity or apoptosis. The murine part is reduced to a minimum with a parallel reduction in potential for immunogenicity. Certolizumab is the only TNFi agent that does not kill activated lymphocytes and monocytes by apoptosis. In spite of all these differences, the safety profile of CZP has been consistent with that already shown for all TNFi.
Curr Opin Rheumatol. 2015;27(2):99-106. © 2015 Lippincott Williams & Wilkins