DOP017: Colectomy-free survival is independent of initial infliximab dosing strategy in hospitalised ulcerative colitis patientsECCO '16 AmsterdamDOP019: Efficacy of autologous haematopoietic stem cell transplantation for refractory Crohn’s diseaseECCO '16 AmsterdamDOP020: Prediction of clinical and endoscopic remission after autologous stem cell transplantation in treatment refractory Crohn’s disease: pooled results from the ASTIC trialECCO '16 AmsterdamDOP021: Long-term efficacy of autologous haematopoietic stem cells transplantation for refractory Crohn’s disease: 10 years of Milan experience without CD34+ cell selectionECCO '16 AmsterdamDOP022: Targeting immune cell metabolism: LYC-30937, a novel therapeutic approach for inflammatory bowel diseaseECCO '16 AmsterdamDOP023: Safety and efficacy of a novel IV targeted pegylated liposomal prednisolone product (Nanocort): results from a phase 2a study in patients with active ulcerative colitisECCO '16 Amsterdam1University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium, 2University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Netherlands, 3Enceladus Pharmaceuticals, Naarden, Netherlands, 4University Clinic RWTH, Experimental Molecular Imaging, Aachen, Germany
Ulcerative Colitis (UC) is a chronic, relapsing inflammatory disease affecting the mucosal lining of the rectum and the colon to a variable extent. Corticosteroids have long been a cornerstone in the treatment of UC, despite considerable side effects including Cushingoid facies and weight gain, acne, hyperglycaemia, insomnia, infections, and osteoporosis after extended use. Nanocort is a novel pharmaceutical composed of prednisolone sodium phosphate enclosed in 100 nm PEGylated liposomes, which, after IV infusion, selectively target and accumulate in inflamed bowel lesions and selectively deliver high and effective concentrations of corticosteroids, thus reducing the required total steroid dose and dosing frequency.
In an exploratory, 2-centre (neoplastic lesions [NL] and BE), randomised, placebo-controlled, observer-blind phase 2a study, the safety and efficacy of Nanocort was evaluated in 18 patients aged 22–63 with moderate-to-severe active UC. Two IV doses of 150 mg Nanocort (n = 14) or saline (n = 4) were given as slow infusions 2 weeks apart. Overall safety (primary endpoint), pharmacokinetics, and efficacy were assessed at weeks 2, 4, 8, and 12 after start of treatment.
The median total Mayo score (tMS, 0–12) at baseline was 10 (range 7–12). At week 4 the Nanocort group showed clear benefit in 70% of the patients with 4 patients out of 13 in remission. Further, 7 out of 13 patients showed a reduction of the endoscopy sub score of ≥ 1 point reaching ≤ 1 point. Rapid effects on partial Mayo score (pMS, 0–9) were shown with persisting remissions in 7/13 patients treated with Nanocort. Remission was defined as a post-treatment MS of ≤ 2 points with all sub scores ≤ 1 point. Typical steroid-related adverse effects were sparse with isolated mild to moderate cases of acne, dyspepsia, nausea, and gastritis. No significant suppression of urinary cortisol was found, nor were there any indications of hyperglycaemia. Some patients experienced infusion reactions probably related to the trial medication. One patient experienced an exacerbation of psoriasis upon withdrawal.
The results of this phase 2a study demonstrate that IV Nanocort can be a safe new therapy with fast and durable therapeutic benefit for patients with active UC without the drawbacks of oral steroid standard-of-care. Larger studies are warranted.
Figure 1. Nanocort effect.
DOP024: Electrical vagus nerve stimulation as an innovative treatment in inflammatory bowel diseasesECCO '16 AmsterdamDOP025: Clinical response to anti-MMP9 antibody (GS-5745) is accompanied by histologic improvement in ulcerative colitisECCO '16 AmsterdamDOP026: The Toll-like-receptor 9 agonist DIMS0150 demonstrates therapeutic efficacy for the patient-reported outcome measures PRO-2 and ClinPRO in moderate-to-severe active ulcerative colitisECCO '16 AmsterdamDOP027: Large-scale drug screen reveals benzimidazole anti-helminthics as potential anti-TNF co-therapyECCO '16 AmsterdamDOP028: Efficacy and safety of biosimilar infliximab after one year: results from a prospective nationwide cohortECCO '16 AmsterdamDOP029: Outcomes of a managed switching programme changing IBD patients established on originator infliximab to biosimilar infliximabECCO '16 AmsterdamDOP030: Elective switching from Remicade® to biosimilar CT-P13 in inflammatory bowel disease patients: a prospective observational cohort studyECCO '16 AmsterdamDOP031: Efficacy of infliximab biosimilar CT-P13 therapy on mucosal healing in ulcerative colitis: data from 2 Central European countriesECCO '16 AmsterdamDOP032: Switching of patients with inflammatory bowel disease from original infliximab (Remicade®) to biosimilar infliximab (Remsima™) is effective and safeECCO '16 AmsterdamDOP033: Immunogenicity profile and predictors of TLs and ADA development of biosimilar infliximab during the first 6 months of the therapy: results from a prospective nationwide cohortECCO '16 AmsterdamDOP034: Comparative effectiveness of infliximab and adalimumab in Crohn’s disease: results from a real-life population-based cohortECCO '16 Amsterdam