Switching From Reference Infliximab to Biosimilar CT-P13 Did Not Change Quality of Life in Stable Inflammatory Bowel Disease Patients.

Background: Quality of life (QoL) data for patients with inflammatory bowel disease switched from the reference infliximab to biosimilar CT-P13 is lacking. This study aims to demonstrate noninferiority for QoL and efficacy after switching. Methods: OoL and clinical efficacy were measured prior to and after 2, 4, and 6 CT-P13 infusions. Results: One hundred seventy-eight patients were included. Noninferiority was established for QoL [ratio 97.95% (95% confidence interval 95.93 to 100.01)] and efficacy [difference -0.02 (95% confidence interval -0.68 to 0.64)]. Five patients reported 6 nonrelated, serious adverse events. Conclusions: Switching from reference infliximab to CT-P13 did not affect the QoL or disease activity and was well tolerated.

Serum concentrations after switching from originator infliximab to the biosimilar CT-P13 in patients with quiescent inflammatory bowel disease (SECURE): an open-label, multicentre, phase 4 non-inferiority trial.

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. FUNDING: Mundipharma.

Blood flow in the hands of a predefined homogeneous systemic sclerosis population: the presence of digital ulcers and the improvement with bosentan.

OBJECTIVES: The aim of the study was to examine the effect of bosentan on blood flow in the hand in a subset of patients who had reduced blood flow relative to healthy subjects. Additionally, the relationship between blood flow in the hands of SSc patients and the presence of digital ulcers (DUs) was assessed. METHODS: SSc patients with a recent history of DUs and healthy subjects were included. Patients were classified into four subgroups: no current DUs or pitting scars, pitting scars only, new DUs or persistent DUs. The hand was categorized into three regions of interest (ROIs) and blood flow was measured by laser Doppler perfusion imaging at baseline, 4 and 12 weeks. Patients who had a reduction in blood flow of >50% relative to healthy control subjects in ROI 1 on baseline were treated with bosentan for 12 weeks. RESULTS: Fifty-two SSc patients and 51 healthy subjects were included in the analysis. There was no significant difference in blood flow in the hand across the patient subgroups at baseline. Sixteen SSc patients had a reduction of blood flow of ≥50% vs healthy subjects and received bosentan. Bosentan significantly (P < 0.05) increased blood flow in the whole hand after 12 weeks compared with baseline. CONCLUSION: No relationship was found between blood flow in the hands and the presence of DUs. After 12 weeks of bosentan treatment, blood flow had increased in the SSc patients but had not normalized to that of healthy subjects. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ (EudraCT number 2010-023908-27).