Clinical response to infliximab after secondary failure with adalimumab or certolizumab pegol in crohn's disease

Purpose: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Three anti‐tumor necrosis factor (TNF) agents are currently approved for the treatment of CD, and while they all have efficacy, many patients lose response. Adalimumab (ADA) and certolizumab pegol (CTZ) have efficacy in the treatment of CD in patients who lose response to infliximab (IFX), but no studies have looked at whether patients who lose response to ADA or CTZ respond to therapy with IFX. The aim of this study was to assess the response rate and tolerability of infliximab in patients who secondarily failed treatment with ADA to CTZ. Methods: This is a retrospective cohort study including patients seen at the University of Miami (Florida, USA). We included consecutive patients with moderate‐to‐severe CD who secondarily failed to respond to either ADA or CTZ, and were subsequently switched to IFX. Patients who underwent surgery for CD within 6 months of the initiation of the IFX were excluded. Data collected for each patient included demographics, phenotype of disease (Montreal classification), CD‐treatment medications, and inflammatory markers. The primary outcome was the response to IFX treatment, as defined by the treating physician's perception of subjective improvement of disease symptoms at 4 and 12 weeks after the first induction dose. The secondary outcome was the development to an infusion reaction to IFX. Results: Twenty‐four patients met inclusion criteria. Their baseline characteristics are shown in Table 1. 18 patients (75%) responded to infliximab after discontinuing ADA or CTZ. The differences in baseline characteristics among patients who did and did not respond to IFX are shown in Table 2. The presence of peri‐anal disease was the only variable that predicted response to IFX after secondarily failing ADA or CTZ (RR 1.9; 95% CI 1.1‐3.1). No patients developed an infusion reaction to IFX. Conclusion: The majority of patients who secondarily fail treatment with ADA or CTZ will subsequently respond to treatment with IFX; these IFX infusions are well‐tolerated. These results also diminish the significance of any potential cross‐reactivity among anti‐TNF antibodies. The presence of peri‐anal disease was associated with a higher rate of response to IFX, which requires further lines of inquiry. A randomized controlled study looking at the efficacy of IFX after ADA or CTZ failure is warranted. (Table Presented).