Certolizumab in the long-term treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis is the most common inflammatory arthritis and continues to have major long-term effects on quality of life. Early and intensive treatment has now become the norm in clinical practice with changes of medication dictated by measuring the presence of continued disease activity. Biologics, particular tumor necrosis factor inhibitors, have a crucial role in the management of very severe disease. Certolizumab is a relatively new tumor necrosis factor inhibitor which uses a novel strategy to neutralize TNF-alpha – the conjugation of tumor necrosis factor specific Fab antibody fragments to polyethylene glycol. Two Phase II and three Phase III randomized controlled trials have evaluated the efficacy and toxicity of certolizumab. More than 2000 patients were enrolled, and followed from 12–52 weeks. The number of patients achieving significant improvements with certolizumab, was indicated by the American College of Rheumatology with a 50% response rate. The risk ratios of achieving this response at 24 weeks was 6.01 (95% confidence interval [CI]: 3.84–9.40). At 52 weeks the risk ratio was 5.27 (95% CI: 3.19–8.71). The number of patients needed to treat, to obtain this benefit at 24 weeks was 4 (95% CI: 3–5). Certolizumab also had important clinical benefits in reducing erosive damage to joints, limiting disability, and enhancing other outcomes of importance to patients such as fatigue. The patient-related benefits were present from the early weeks of treatment. The clinical trials showed serious adverse events, including infections, which were more frequent for certolizumab. The most common adverse events comprised upper respiratory tract infections, hypertension, and nasopharyngitis. The balance of evidence suggests that certolizumab is equivalent to other tumor necrosis factor inhibitors, though no head-to-head trials have been undertaken. Having several effective treatments available, benefits patient choice, because the frequency and route of administration of these treatments varies. Furthermore, as intolerance and antibody development against existing biologics is not uncommon, having several agents allows opportunities to switch from one inhibitor to another.

Keywords:

• rheumatoid arthritis
• certolizumab
• anti-TNF

Disclosures

Abdul Khan has received no external grants or personal funding from any industrial sponsor. David L Scott receives grant funding support from Arthritis Research UK and The National Institute for Health Research. In the past 3 years Professor Scott has received no personal funding from any industrial sponsor.