DOP004: Epigenetic control of colonic epithelial antigen processing, barrier function, and the microbiome via methyl-CpG binding domain protein 2ECCO '16 AmsterdamDOP005: A role for IL1 in mediating intestinal inflammation in IL10 receptor deficiency in mice and humansECCO '16 AmsterdamDOP006: Gut-homing adipose tissue T-cells might influence intestinal barrier function in Crohn’s disease and obesityECCO '16 AmsterdamDOP007: Interleukin-10 inhibits human IFNγ and IL-17-producing T helper cells indirectly by controlling antigen-presenting cell functionECCO '16 AmsterdamDOP008: Human intestinal Vδ2+ T-cells acquire antigen-presenting potency upon exposure to microbial phosphoantigen: modulation by mucosal inflammation and vedolizumab therapyECCO '16 AmsterdamDOP009: An autoimmunity-associated variant in PTPN22 protects from disease onset in mouse models of colitisECCO '16 AmsterdamDOP010: Frequency and characteristics of infusion reactions during biosimilar infliximab treatment in inflammatory bowel diseases: results from a Central European nationwide cohortECCO '16 AmsterdamDOP011: Early immunomodulator exposure and the long-term outcome of Crohn’s disease: target for changing the natural historyECCO '16 AmsterdamDOP012: Do ulcerative colitis patients treated with corticosteroids at diagnosis really have a more aggressive disease course?ECCO '16 AmsterdamDOP013: A 104 week mucosal healing assessment of symptomatic small bowel Crohn’s diseaseECCO '16 AmsterdamDOP014: Nutritional optimisation of presurgical Crohn’s disease patients with enteral nutrition significantly decreases length of stay and need for a stomaECCO '16 AmsterdamDOP015: Myenteric plexitis is a risk factor for endoscopic and clinical postoperative recurrence after ileocolonic resection in Crohn’s diseaseECCO '16 AmsterdamDOP017: 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.