Successful induction of clinical response and remission with certolizumab pegol in Crohnʼs disease patients refractory or intolerant to infliximab: A real-life multicenter experience of compassionate use

To the Editor: Tumor necrosis factor–alpha (TNF-α) is an important proinflammatory cytokine that plays a fundamental role in Crohn's disease (CD) pathogenesis.1 Targeting TNF-α has been a breakthrough in the treatment of CD patients.2 In particular, infliximab, a chimeric anti-TNF monoclonal antibody, has been widely used in inducing and maintaining response and remission in patients with moderate to severe CD. However, some patients treated with infliximab experience a loss of efficacy over time or become intolerant of infliximab. 2,3 Certolizumab pegol is a pegylated humanized Fab′ fragment with a high binding affinity for TNF-α that is effective in the treatment of patients with CD, either naive or previously treated with infliximab. 4,5 No specific studies have so far been published assessing its efficacy specifically in patients who had responded to infliximab and then lost that response or were intolerant to the agent. Certolizumab pegol has been available for compassionate use in Italy since 2006 According to local legislation, a patient to be eligible for compassionate use of an investigational agent must have undergone every other authorized therapeutic option. The efficacy and safety of certolizumab pegol was evaluated in the induction of remission in adult CD patients who have symptoms despite Infliximab therapy or who cannot take infliximab because of adverse events. Consequently, our patient population consisted of subjects who were refractory or who had lost response or were intolerant to infliximab. Clinically active CD patients [as measured by a Harvey Bradshaw Index score (HBI) > 4] received an induction dose of 400 mg of certolizumab pegol subcutaneously at weeks 0, 2, and 4 and subsequently a maintenance regimen of 400 mg every 4 weeks. Clinical response was assessed based on HBI at week 4. Remission was defined as an HBI ≤ 4 points from baseline, whereas response was defined as a reduction of HBI ≥ 3 points.