Purpose: Anti-TNF agents are effective in the treatment of Crohn's disease (CD). However, development of neutralizing antibodies can potentially reduce the clinical response rate.1 Certolizumab pegol, a PEGylated Fc-free Fab’ with high potency for human TNFα, was evaluated in two recent pivotal Phase III trials in CD (PRECiSE 1 and 2) in which the effect of neutralizing antibodies on efficacy and safety was analyzed. Methods: Subcutaneous certolizumab pegol 400 mg was administered at Weeks 0, 2, 4, then every 4 weeks up to Week 24. Plasma samples were considered neutralizing if they reversed the ability of certolizumab pegol to block interleukin-6 production in response to TNFα in HeLa cells. Patients with ≥1 neutralizing sample were classed as antibody positive (Ab+). Clinical response was defined as a decrease in CD Activity Index (CDAI) score of ≥100 points (at Weeks 6 and 26 PRECiSE 1 and Week 26 in PRECiSE 2). Influence of antibody status on the incidence of adverse events (AEs) was also examined. Results: Clinical response rate by neutralizing antibody status was determined for patients who received continuous treatment with certolizumab pegol (Table). There was no reduction in the proportion of responders in the Ab+ cohort relative to the antibody negative (Ab-) cohort in either trial. Most AEs occurred with a similar incidence regardless of neutralizing antibody status. AEs that occurred more frequently in patients after development of antibodies were viral gastroenteritis (3%[ Ab+] vs 1%[ Ab-]) and anemia (5% vs 3%). AEs occurring more frequently in Ab- patients were nausea (9%[ Ab-] vs 2%[ Ab+]), pyrexia (8% vs 4%), and headache (17% vs 5%). No hypersensitivity signals (eg, injection-site reactions, injection-site pain, influenza-like illness or rash) were associated with the presence of antibodies.TableConclusion: The development of neutralizing antibodies to certolizumab pegol does not appear to have a marked effect on clinical response rates in patients with CD. The frequency of AEs was similar in Ab− and Ab+ patients. Patients in this trial showed no indication of hypersensitivity reactions. This research was funded by UCB.