Certolizumab Pegol

Abstract

Certolizumab pegol is a PEGylated humanized Fab' monoclonal antibody that targets and neutralizes both membrane-bound and soluble tumor necrosis factor (TNF)-alpha, preventing inflammation and consequently the destruction of cartilage and bone. Certolizumab pegol has a relatively long elimination half-life of approximately 2 weeks, allowing subcutaneous administration once every 2 or 4 weeks. In two randomized, phase III trials in patients with active rheumatoid arthritis despite previous methotrexate therapy (RAPID 1 and 2), the combination of subcutaneous certolizumab pegol 400 mg at weeks 0, 2, and 4, followed by a 200 or 400 mg dose every 2 weeks and a stable dosage of methotrexate, was more effective than placebo plus methotrexate for improving the signs and symptoms of arthritis at weeks 24 (RAPID 1 and 2) and 52 (RAPID 1), according to American College of Rheumatology (ACR) criteria. Improvements in ACR response rates were seen as early as 1 week and at all timepoints measured up to 52 weeks. In RAPID 1 and RAPID 2, radiographic progression was also significantly inhibited with certolizumab pegol plus methotrexate treatment compared with placebo and methotrexate according to van der Heijde modified Total Sharp Scores at 24 and 52 weeks after treatment initiation. In patients with active rheumatoid arthritis who had previously failed to respond to treatment with > or = 1 disease-modifying anti-rheumatic drug, certolizumab pegol 400 mg every 4 weeks as monotherapy effectively improved ACR responses at all measured timepoints up to 24 weeks, according to data from the randomized, phase III FAST4WARD trial. Certolizumab pegol was generally well tolerated in combination with methotrexate or as monotherapy in phase III trials in patients with rheumatoid arthritis, with most adverse events being of mild to moderate intensity. Infections were the most frequently reported adverse events.