BACKGROUND & AIMS: This study compared pharmacokinetics, symptomatic and endoscopic efficacy, safety, and immunogenicity of a subcutaneous formulation of the infliximab biosimilar CT-P13 (CT-P13 SC) vs intravenous CT-P13 (CT-P13 IV) in patients with inflammatory bowel disease (IBD). METHODS: This randomized, multicenter, open-label, parallel-group, phase 1 study enrolled tumor necrosis factor inhibitor-naïve patients with active ulcerative colitis (total Mayo score 6-12 points with endoscopic subscore 2) or Crohn's disease (Crohn's Disease Activity Index 220-450 points) at 50 centers. After CT-P13 IV induction at Week (W) 0/ W2, patients were randomized (1:1) to receive CT-P13 SC every 2 weeks (q2w) from W6 to W54 or CT-P13 IV every 8 weeks from W6 to W22. At W30, all patients receiving CT-P13 IV switched to CT-P13 SC q2w until W54. The primary endpoint was noninferiority of CT-P13 SC to CT-P13 IV for observed predose CT-P13 concentration at W22 (C trough,W22 ), concluded if the lower bound of the 2-sided 90% confidence interval (CI) for the ratio of geometric least-squares means exceeded 80%. RESULTS: Overall, 66 and 65 patients were randomized to CT-P13 SC and CT-P13 IV, respectively. The primary endpoint of noninferiority was met with a geometric least-squares means ratio for C trough,W22 of 1154.17% (90% CI 786.37-1694.00; n ¼ 59 [CT-P13 SC]; n ¼ 57 [CT-P13 IV]). W30/W54 clinical remission rates were comparable between arms. Other efficacy,
Diabetes is a metabolic disease leading to the development of numerous health complications. In developed countries, it is the main cause of blindness, end-stage renal disease, and non-traumatic amputation of the lower limbs. Neuropathy is the most common chronic complication of diabetes. A long-term course of a metabolically unbalanced disease causing damage to the autonomic nervous system of the digestive tract results in the development of many complications, such as intensification of gastro-oesophageal reflux disease, gastroparesis, chronic diarrhoea or faecal incontinence.
The (13)C-methacetin breath test could be a promising noninvasive tool for excluding at least F1 fibrosis in NAFLD patients.
Background Two randomised controlled trials of a novel subcutaneous (SC) formulation of infliximab in patients with active rheumatoid arthritis1 and in patients with active Crohn’s disease (CD) and ulcerative colitis (UC)2 confirmed comparable clinical efficacy and safety of CT-P13 SC with CT-P13 intravenous (IV) up to Week 30. We now present the efficacy, pharmacokinetics (PK) and safety of CT-P13 SC over 1-year in the active CD and UC trial, including the outcomes of switching from CT-P13 IV to CT-P13 SC. Methods After loading doses of IV 5 mg/kg at Weeks 0 and 2, patients were randomised at Week 6 to receive either SC 120 mg (<80 kg) or 240 mg (≥80 kg) every 2 weeks (SC arm), or continued on IV 5 mg/kg every 8 weeks (IV arm). From Week 30, IV 5 mg/kg was switched to either SC 120 or 240 mg based on the patients’ body weight at Week 30. Patients who initially responded but experienced loss-of-response at Week 30 or beyond, were dose-escalated to SC 240 mg every 2 weeks. Results A total of 131 patients were randomised (66 to the SC arm and 65 to the IV arm); of whom, 105 (80.2%) patients completed the Week 54 visit (55 in the SC arm and 50 in the IV arm). The mean CDAI and partial Mayo scores decreased over time in the 2 arms until Week 30 and comparable improvement in clinical activity was observed at Week 54 after switching the remaining IV patients to SC (Figure 1 and 2). The rates of clinical response and remission were also maintained at Week 54 and the rate of mucosal healing in combined CD and UC was further improved at Week 54 (Table 1). The mean pre-dose serum concentrations in the IV arm increased to a similar level to SC arm after switching and maintained consistent levels until Week 54 (Figure 3). The safety profiles during the maintenance phase and on or after Week 30 were generally comparable between the 2 arms (Table 1). All of the localised injection site reactions were grade 1 or 2 in intensity and majority of patients recovered without any treatments. Conclusion These results of CT-P13 SC 1-year study in active CD and UC show comparable efficacy and safety of the SC and IV formulations, which were not affected by a switch of IV patients to SC route. The PK as manifested by trough concentrations of the drug, increased after switching from IV to SC. These observations support the first infliximab SC formulation as a viable therapeutic agent to expand patients’ treatment options. References
P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn’s disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.
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