P407 A Phase IB/IIA study of remestemcel-L, an allogeneic bone marrow derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: An interim analysis

Abstract

i399 time of colonoscopy. Patients were included if they had medically re-fractory UC defined as an established diagnosis for at least, 6 months prior to study enrollment and had lost response to at least one mono-clonal antibody in the past. Patients were evaluated with validated clinical and endoscopic scoring systems at, 2 weeks, 6 weeks, and, 3 months post MSC delivery. Patients randomized to control crossed over at, 3 months to receive MSC treatment and followed the same schedule for post MSC evaluation. Results: A total of six patients were enrolled and treated;, 4 were rand-omized to treatment and, 2 to placebo. All had been on prior anti-TNF or anti integrin-therapy. There were no adverse and serious adverse events related to investigational product. In the treatment group (n=4), the Mayo score and Mayo endoscopic severity score decreased in all patients by two weeks after MSC delivery. By six weeks post MSC treatment, all treated patients had achieved clinical and endoscopic remission as defined by the Mayo score and Mayo endo-scopic severity score. Patient reported number of daily bowel movements decreased as did urgency and presence of blood in the stool. With regard to patient reported outcomes, at three months, based on the inflamma-tory bowel disease patient reported treatment impact (IBD-PRTI), all patients were extremely satisfied or satisfied with their MSC treatment. Treated response was described as excellent or good in all patients. In the control group (n=2), the Mayo score did not decrease. Patient reported number of daily bowel movements increased as did the number reporting blood in their stool; urgency remained unchanged. With regard to patient reported outcomes, at three months, based on the IBD-PRTI, one patient was neutral, and one patient was dissatisfied. Treated response was described as poor or unchanged in control patients. Conclusion: MSCs offer a safe alternative therapeutic for the treatment of medically refractory UC. Early data suggests improved clinical and endoscopic scores by as early as two weeks following MSC delivery. Background: Infliximab (IFX) is increasingly used in the management of moderate to severe ulcerative colitis (UC) and as a 'rescue' treatment for acute severe UC (ASUC) but primary non response (PNR) and colectomy rates remain significant. Reasons for IFX treatment failure in ASUC are multifactorial but immunogenicity and faecal loss of drug are thought to be important factors. Emerging evidence suggests accelerated 'rescue' IFX dosing may be more effective. The aim of this work was to establish if a relationship exists between faecal IFX levels, disease activity, and clinical outcomes early in IFX treatment. Methods: Patients with UC were prospectively recruited following initiation of IFX and designated as ASUC or non-ASUC based on Truelove and Witt's criteria. Stool and serum were collected on days, 0, 7, 14, 28 and, 42 after initiation of IFX. Additional samples on days, 1-5 after IFX were obtained from inpatients. Albumin and CRP results were extracted from electronic patient records. Faecal calprotectin (FC) was measured using ELISA (CALPROLAB). Faecal IFX within the first, 2 weeks of treatment was analysed using a Promonitor-IFX-1DV ELISA assay, performed on the Triturus ELISA instrument. R studio was used to calculate areas under the curves of the time series. Spearman's rank correlation test was used for correlation analysis. Results:, 20 patients were recruited, 12 with ASUC. Faecal IFX correlated strongly with FC (ρ=0.793;p<0.001) (Fig., 1), and moderately with CRP (ρ=0.51;p=0.02), and serum albumin (ρ=-0.51;p=0.02). The correlation was strongest between faecal IFX and FC within in the first week (ρ=0.93;p<0.001), and less strong for crp (ρ=0.481;p=0.037) and albumin (ρ=-0.474;p=0.04). Higher faecal IFX was associated with increased colectomy and PNR rates but this did not reach statistical significance (p=0.098). A rapid decline in median FC was seen after initiation of IFX with a rebound rise in FC observed at day, 3 of IFX treatment (Fig. 2).