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.

The efficacy of standard laxative use for the prevention and treatment of opioid induced constipation during oxycodone use: a small Dutch observational pilot study.

BACKGROUND: Dutch clinical guidelines recommend that a standard laxative treatment (SLT) should be prescribed concomitantly when starting opioid treatment to prevent opioid-induced constipation (OIC). METHODS: Clinical evidence for SLT in the treatment of OIC is lacking, therefore an observational pilot study was performed to explore the efficacy and tolerability of SLT on OIC in patients treated with the opioid oxycodone. RESULTS: Twenty-four patients (58% female, median (range) age 65 (39-92)) were included in this pilot study. The analysis showed that 9 out of 21 patients (43%) were non-responders to SLT. When also taking into consideration patients tending to develop diarrhea 75% of patients are non-responsive to SLT. CONCLUSION: This pilot study indicates that optimal laxative therapy (SLT) might not be effective and feasible for the prevention and treatment of OIC.

Treatment with prolonged-release oxycodone/naloxone improves pain relief and opioid-induced constipation compared with prolonged-release oxycodone in patients with chronic severe pain and laxative-refractory constipation.

PURPOSE: Laxative-refractory opioid-induced constipation (OIC) is defined as OIC despite using 2 laxatives with a different mechanism of action (based on the Anatomical Therapeutic Chemical Classification System level 4 term [contact laxatives, osmotically acting laxatives, softeners/emollients, enemas, and others]). OIC has a significant impact on the treatment and quality of life of patients with severe chronic pain. This noninterventional, observational, real-life study in Belgium investigated the efficacy of prolonged-release oxycodone/naloxone combination (PR OXN) treatment regarding pain relief and OIC compared with previous prolonged-release oxycodone (PR OXY) treatment for laxative-refractory OIC in daily clinical practice. METHODS: Laxative-refractory OIC patients with severe chronic pain were treated with PR OXN for 12 weeks (3 visits). Pain relief (assessed on a numerical rating scale) and OIC (assessed by using the Bowel Function Index [BFI]) were evaluated at each visit. A responder was defined as a patient who had: (1) no worsening of pain at the last visit compared with visit 1 or a numerical rating scale ≤4 at visit 3/last visit; and (2) a reduction in BFI ≥12 units at visit 3/last visit compared with visit 1; or (3) a BFI ≤28.8 at visit 3/last visit. FINDINGS: Sixty-eight laxative-refractory OIC patients with severe chronic pain (mean (sd) age 59.8 (13.3) years, 67.6% female and 91.2% non-malignant pain) were treated for 91 days with PR OXN (median daily dose, 20 mg). Treatment with PR OXN resulted in a significant and clinically relevant decrease of pain of 2.1 units (P < 0.001; 95% CI, 1.66-2.54) and of BFI by 48.5 units (P < 0.001; 95% CI, 44.4-52.7) compared with PR OXY treatment; use of laxatives was also significantly reduced (P < 0.001). Approximately 95% of patients were responders, and quality of life (as measured by using the EQ-5D) improved significantly. Adverse events were opioid related, and PR OXN treatment was well tolerated. IMPLICATIONS: Treatment with PR OXN resulted in a significant and clinically relevant reduction in OIC compared with previous PR OXY treatment for these patients with severe chronic pain and laxative-refractory OIC. Treatment with PR OXN also resulted in a significant improvement in pain relief and quality of life. ClinicalTrials.gov identifier: NCT01710917.