Efficacy and Safety of Certolizumab Pegol in patients with active Crohnʼs Disease who previously lost response or were intolerant to Infliximab: Open-Label induction results of the WELCOME Study

Abstract

The availability of new anti-tumor necrosis factor (TNF-α) agents has made it increasingly common for patients with Crohn's disease (CD) to switch therapies. Current guidelines, however, provide little indication of the expected outcomes of such a strategy. The purpose of this analysis was to assess Week 6 response rates to certolizumab pegol (CZP) in patients with CD who have responded to infliximab (IFX) but who are no longer responding or who have developed intolerability due to acute or delayed infusion reactions. WELCOME is Phase IIIb, multicenter, 26-Week open-label trial Evaluating the clinical benefit of certoLizumab pegol induCtiOn and Maintenance in patients suffering from CD with prior loss of response or intolErance to IFX. Two periods are defined: an open-label induction (CZP 400 mg, Weeks 0, 2, and 4) and a double-blind maintenance phase (CZP 400 mg, Weeks 6-24). Patients with a CD Activity Index (CDAI) score of 220-450 points and a history of IFX failure (any reason) were randomized to CZP 400 mg maintenance either every 2 or every 4 weeks from Week 6. Patients withdrawing (any reason) before Week 6 were considered to be nonresponders. Nonresponders at Week 6 were withdrawn. The primary endpoint was defined as the rate of response (decrease in CDAI score ≥ 100 points) at Week 6. Remission was defined as a CDAI score of ≤ 150 points. In total, 539 patients were enrolled. Median CDAI score at baseline was 293 points (interquartile range: 257.3-349.5). At Week 6, 62.2% (57.9-66.3) (intent-to-treat analysis) of patients achieved response and 39.3% (35.2-43.6) achieved remission. These rates were comparable to those in PRECiSE 2 (64.1% in the overall population and 53.9% in patients previously exposed to IFX),1 suggesting that prior IFX exposure may not reduce response to CZP induction. One-third of patients had responses by Week 2 (33.2%); at Week 4, 43.8% were responders. No new safety concerns were identified. Week-6 data from the WELCOME study indicate that the majority of patients with prior exposure to IFX respond to CZP. CZP is an additional treatment option in patients with CD who have had previous biologic exposure.