Maarten Cozijnsen

76 Results Infliximab treatment reduces systemic and intestinal inflammation more than prednisolone treatment After ten weeks of treatment, infliximab treatment established endoscopic remission (SESCD < 3) in 3 out of 5 patients, reduced calprotectin levels below 250 µg/g in 4 out of 6 patients, and 3 out of 6 patients were in clinical remission (PCDAI < 10). Prednisolone treatment, on the other hand, achieved endoscopic remission in only 1 out of 4 patients (p = 0.52), 1 out of 5 patients had calprotectin below 250 µg/g (p = 0.24) and 2 out of 5 patients were in clinical remission (p = 1.00) (Figure 1A). Infliximab treatment resulted in a more homogeneous decrease in leukocyte concentrations in peripheral blood when compared to prednisolone (Figure 1B). It decreased neutrophil concentrations in all patients with minimal variation at week 10 (median change -4.6*10^9/L [range -2.5 to -5.3], p = 0.04), while changes in neutrophil concentrations after prednisolone treatment were more heterogeneous (median change 0.5*10^9/L [range -3.5 to 4.7], p = 0.72; infliximab vs prednisolone: p = 0.03). A similar, less pronounced change is seen in monocyte concentrations (infliximab: median decrease -0.65*10^9/L [range -0.43 to -0.76], p = 0.04; prednisolone: median decrease -0.13*10^9/L [range 0.2 to -0.45], p = 0.47; infliximab vs prednisolone: p = 0.03). The impact of infliximab and prednisolone treatment on lymphocyte concentrations were more comparable (infliximab: median decrease -0.37*10^9/L [range -0.09 to -0.83] p = 0.04; prednisolone: median decrease -0.41*10^9/L [range 0.10 to -1.35], p = 0.14; infliximab vs prednisolone: p = 0.91). Basophil and eosinophil concentrations in peripheral blood did not change after infliximab or prednisolone treatment (all p > 0.05). Whole blood RNA expression revealed 949 significantly modulated genes in blood leukocytes at week 10 during infliximab treatment compared to baseline. In contrast, no significant changes in whole blood mRNA expression were detected in patients after prednisolone treatment. Similarly, infliximab treatment resulted in decreased concentrations of 34 out of 92 inflammatory proteins in serum, whereas none of these 92 inflammatory proteins were significantly changed in concentration after prednisolone treatment (Supplementary Table 1). In the coming three paragraphs we will highlight the three most dominant pathways specifically regulated by infliximab treatment but not by prednisolone treatment. Notably, we did not see significant modulation of Th17 related genes in either treatment group (such as IL17A , IL21 , IL22 , IL23A , STAT3 , RORC ) besides in the infliximab group downregulation of IL17RA and IL21R in RNA of blood leukocytes. With respect to monocytes, we saw a downregulation of RNA expression of CD14 and CD68 in blood leukocytes after 10 weeks in line with the decreased monocyte concentrations in peripheral blood.