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).

Identifying error pathways during elbow and knee replacements.

The aim of our study was to identify errors and error pathways during joint replacements and to propose improvements. A time-action and error analysis method was adapted for use during surgery. The error analysis consisted of identifying all possible errors, determining error paths presented in an error chart, quantifying errors, and determining the impact of errors. This method was used to evaluate joint replacements. We evaluated five knee and 11 elbow replacements done by two experienced surgeons. The main error for elbow replacements was caused by inadequate instruments. The main error for knee replacements was caused by inexperienced nurses being unfamiliar with guiding instruments. The time-action analysis showed a large variation in procedure duration. The main surgical limitations for both procedures were waiting caused by the cementing process and waiting caused by inexperienced scrub nurses. Our study identified errors and surgical limitations during joint replacements by using time-action and error analysis. Placement of both prostheses will benefit from new fixation techniques, a more experienced nursing staff, and more organized instrument tables.

Factors influencing the surgical process during shoulder joint replacement: time-action analysis of five different prostheses and three different approaches.

BACKGROUND: To evaluate the per-operative process of shoulderjoint replacement, time-action analysis can be used. MATERIAL/METHODS: Forty procedures performed by 7 surgeons with different experience using 5 different prostheses and 3 different surgical approaches were analyzed. RESULTS: The surgical procedures showed a large variation in, for example, duration, tasks of team members, and protocol used. The surgical procedure was influenced by several factors, such as the prosthesis used, the surgical approach, the patient's condition, and the experience of the surgeon. Exposure of the glenoid was difficult and several retractors were needed, which were held by an extra assistant or clamped to the table or the surgeon. Two main limitations were seen in all procedures: repeated actions and waiting. Also, five errors could be identified. None of the alignment instruments was completely reliable and they allowed the surgeon to make major errors. CONCLUSIONS: Better alignment instruments, pre-operative planning techniques, and operation protocols are needed for shoulder prostheses. The training of resident surgeons should be focused on the exposure phase, the alignment of the humeral head, the exposure of the glenoid, and the alignment of the glenoid. Evaluating the surgical process using time-action analysis can be used to determine the limitations during surgical procedures. Furthermore, it shows the large variation in factors affecting surgical performance, indicating that a system approach is needed to improve surgical outcome.

Evaluation of humeral head replacements using time-action analysis.

New surgical technologies are often introduced without objective evaluation of their efficiency. Commonly, their results are only related to surgical outcome and complication rate. In this study, time-action analysis was applied to evaluate the per-operative process and to measure surgical performance during 8 humeral head replacements. An overview of the operative theater and a detailed view were recorded on video simultaneously. The duration and number of actions grouped to functions, limitations, and repeated actions were determined. The duration and number of performed actions varied between procedures. The efficiency of the procedure, defined as the percentage of goal-oriented functions, was about 55%. Repeated actions were frequently observed during the alignment and insertion phase. We conclude that time-action analysis can be used to evaluate surgical performance objectively. Limitations of the surgical process that can be improved could be identified. These findings enable the evaluation of new operative techniques, protocols, and instruments.