Background: Crohn's disease (CD) is an inflammatory disorder that can affect any portion of the gastrointestinal tract, from the mouth to the rectum. The American Gastroenterological Association recommends that treatment with anti-tumor necrosis factor (TNF)-alpha be considered in patients with moderate to severe CD refractory to concomitant aminosalicylates, corticosteroids, or immunosuppressive treatment, or who have contraindications to or poor tolerance of these agents. Anti-TNF-alpha agents available in the United States for the management of CD are infliximab, adalimumab, and certolizumab pegol. The latter is a recombinant humanized antibody Fab' fragment against TNF-alpha. It is conjugated with a 40-kDa polyethylene glycol molecule to increase the t(1/2) of the treatment to approximately 2 weeks.
Objective: The objective of this review was to extract and assess all relevant available data on the efficacy and tolerability of certolizumab pegol in the treatment of CD.
Methods: Searches of MEDLINE and International Pharmaceutical Abstracts from 1985 to March 3, 2009, were conducted using the key terms certolizumab pegol, CDP870, and Crohn's disease. Data from all available clinical trials published in English and ongoing trials were included in this review. The reference lists of the identified articles were searched for additional references. Data from abstracts presented at the annual meetings of the American College of Gastroenterology and Digestive Disease Week from 2004 to 2008 were reviewed and included if relevant.
Results: A total of 8 studies were included in this review (1474 patients). In Phase II trials, there were no significant differences between certolizumab pegol and inactive vehicle (placebo) in week-4 or week-12 clinical response or remission rates. In the first of 2 Phase III clinical trials, certolizumab pegol was associated with significantly greater rates of response compared with placebo at weeks 6 (37% vs 26%; P = 0.04) and 26 (22% vs 12%; P = 0.05) of induction treatment (data from patients with baseline CRP concentrations > or =10 mg/L). Response was defined as a decrease from baseline in CD activity index > or =100 at week 6 and at both weeks 6 and 26 in patients with baseline C-reactive protein > or =10 mg/L. Remission rates were not significantly different between the 2 groups. In the second Phase III trial, the proportion of patients in whom response was sustained up to 26 weeks was significantly greater with certolizumab pegol compared with placebo (63% vs 36%; P < 0.001). The tolerability profile of certolizumab pegol was similar to those of other anti-TNF-alpha agents and included an increased risk for infections (including opportunistic infections [eg, tuberculosis]) compared with placebo. Infusion and injection-site reactions were infrequent (3%) with certolizumab pegol treatment. The most common adverse events reported with certolizumab pegol treatment included upper respiratory infection (20%), immunogenicity (8%), and urinary tract infection (7%). No new unanticipated adverse events emerged during the 30-month tolerability follow-up. Certolizumab pegol is being assessed in patients with CD refractory to other medications, including other biologic agents.
Conclusions: Based on the findings from the present review, certolizumab pegol had moderate efficacy in the treatment of moderate to severe, active CD. In well-designed Phase III clinical trials, certolizumab pegol was associated with significantly greater response rates compared with placebo at weeks 6 and 26 of induction treatment. In patients who responded to the 6-week induction, certolizumab pegol administered as a monthly subcutaneous injection was effective in maintaining CD response and remission. Findings from studies of certolizumab pegol in refractory CD are awaited.