Background Combining vedolizumab with a rapid-onset drug such as cyclosporine is a novel combination treatment for severe steroid-resistant ulcerative colitis (UC). This prospective study describes the efficacy and safety of cyclosporine in conjunction with vedolizumab in patients with severe, steroid-resistant UC with 1 year of follow-up. Methods Seventeen steroid-resistant UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Clinical and endoscopic response, remission rates, and colectomy-free survival were the primary endpoints. Secondary endpoints included biochemical response and remission with C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin. Results Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab. By week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission. At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission. Among the 10 patients in endoscopic remission, 8 (80%) reached histological remission. Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively. No serious adverse events were reported. Conclusions Bridging cyclosporine to vedolizumab in severe, steroid-refractory UC patients is effective and safe at inducing and maintaining clinical, endoscopic, and biochemical response and remission up to 52 weeks of follow-up. Larger prospective studies are warranted.

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Background/Aim. Colorectal cancer (CRC) is one of the most common cancers in the population, often leading to lethal outcome. Myeloid-derived suppressor cells (MDSC) belong to a heterogeneous group of immature cells that are thought to have an immunosuppressive effect that may aid in tumor development and spread. The aim of this study was to analyze the frequency and significance of MDSC like cells at different stages in patients with CRC. Methods. We analyzed a blood samples in 83 patients at different stages of the disease and 12 healthy subjects who made up the control group. MDSC like cells were detected and enumerated in peripheral blood samples of the participants based on the immunophenotypic characteristics of the cells. Results. A statistically significant increase in the absolute and relative number of polymorphonuclear MDSC like cells (PMN-MDSC like cells) in peripheral blood was observed in total patients with CRC compared to the healthy, control group (p <0.0001). No statistically significant increase was observed in mononuclear MDSC like cells (M-MDSC like cells) when analyzed without stage stratification (p> 0.05). Analyzing the relative and absolute number of PMNMDSC like cells according to the stages of CRC disease (TNM classification), a statistically significant difference was observed between the control group and patients in stage III and IV disease (p=0.0005 vs p=0.0003 and p<0.0001 vs p<0.0001, respectively), as well as comparing values in stage I and II patients with PMN-MDSC like cells values in stage IV CRC (p=0.0161 vs p<0.0001 and p=0.0065 vs p<0.0001, respectively). A statistically significant difference in the relative and absolute number of M-MDSC like cells was observed only in patients between stage II and IV disease (p = 0.0014 and p = 0.0002, respectively). The highest number of MDSC like cells were observed in stage IV of the disease according to the TNM classification. Positive correlation between the presence of these cells and the number of organs affected by metastatic changes was observed (p<0.0001 for relative and absolute number of PMN-MDSC like cells and p=0.003 and p=0.0004 for relative and absolute number of M-MDSC like cells). Conclusion. CRC patients had a statistically significant increase in PMN-MDSC like cells compared to healthy controls. The increase in absolute and relative numbers of these cells mostly follows the growth and progression of CRC, while a statistically significant difference in 4 the number of M-MDSC like cells is observed only between stages II and IV of the disease. The absolute and relative numbers of both subtypes of MDSC-like cells correlate with the number of organs affected by CRC metastases.

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