Background: Biological treatment of chronic inflammatory diseases has improved patient outcomes but increased health-care costs. Switching patients from originator infliximab to a biosimilar can reduce costs, but prospective data about pharmacokinetics and potential immunogenicity are scarce. We aimed to show that infliximab serum concentrations with biosimilar CT-P13 are non-inferior to those with originator infliximab after switching from originator infliximab in patients with inflammatory bowel disease.
Methods: SECURE was a prospective, open-label, interventional, non-inferiority, multicentre, phase 4 trial at 13 academic and non-academic sites in Belgium and the Netherlands. Eligible participants were aged 18 years or older, had ulcerative colitis or Crohn's disease, were in clinical remission, and were on continuous treatment with originator infliximab for more than 30 weeks. Patients were switched from originator infliximab to CT-P13 at a dose and infusion duration identical to those of originator infliximab (ie, ∼5 mg/kg every 7-9 weeks). Patients were followed up for 16 weeks after switching, with serum concentrations of infliximab measured at baseline (before the first dose of CT-P13), 8 weeks, and 16 weeks. The primary endpoint was serum concentrations of infliximab 16 weeks after switching, assessed separately in patients with ulcerative colitis and those with Crohn's disease in the per-protocol population, which included all patients with available serum concentrations and without major protocol violations. A non-inferiority margin of 15% was set (the null hypothesis was that the geometric mean of the ratio of serum infliximab concentrations at 16 weeks to those at baseline was 85% or less). Safety analyses were done in the safety population, which included participants who received at least one dose of CT-P13 and attended at least one safety assessment after that dose. This trial is registered at www.ClinicalTrialsRegister.eu, number 2014-004904-31, and is completed.
Findings: Between June 5, 2015, and April 6, 2016, 120 consecutive patients with inflammatory bowel disease were recruited: 59 with ulcerative colitis and 61 with Crohn's disease. 46 patients with ulcerative colitis and 42 patients with Crohn's disease comprised the per-protocol population. The geometric mean ratio of serum infliximab concentrations at week 16 (CT-P13) compared with those at baseline (originator) was 110·1% (90% CI 96·0-126·3) in patients with ulcerative colitis and 107·6% (97·4-118·8) in those with Crohn's disease. In both cases, the lower bound of the 90% CI was higher than the prespecified non-inferiority margin of 85%. Six serious adverse events were reported in six patients. Only one of these adverse events, a perianal abscess, was judged to be related to study treatment.
Interpretation: Switching to CT-P13 is safe and well tolerated in patients with inflammatory bowel disease in remission. Future trials should assess switching to CT-P13 in patients with active disease.
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