P939 Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Histologic Changes in Lymph Nodes

Abstract

Abstract Background Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on these therapies is unknown. We describe histologic changes in lymph nodes from patients with UC who were treated with ozanimod and underwent subsequent colectomy due to treatment-refractory disease. Methods This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who were treated with ozanimod within the 2 months prior to colectomy and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens were reviewed blindly by a hematophatologist (JXC) and an expert GI pathologist (CRW). Histopathological parameters were scored and demographic and clinical data were recorded. Results Of forty-five patients treated with ozanimod at our center, 6 (13%) required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were also examined. Demographic and clinical data are summarized in Table 1. The duration of ozanimod therapy prior to surgery ranged from 6 to 24 weeks. Lymph nodes from patients treated with ozanimod had significantly greater extent of sinus dilatation than control patients (1.5 vs 0.67, p=0.022), they also had significantly more sinus histiocytosis (2.67 vs 1.67, p=0.03) (Figure 1). There was a tendency towards more Castleman-like angiotrophic hyperplasia (1.5 vs 1, p=0.34), plasma cell infiltration (1.5 vs 0.67, p=0.26) and subcortical interfollicular expansion (1.5 vs 0.83, p=0.1) in ozanimod treated patients. Patients treated with ozanimod and controls showed similar amounts of monomorphic lymphoid cells (1.3 vs 1.5, p=0.7), follicular hyperplasia (1 vs 1.1, p=0.8) and vascular proliferation (1.5 vs 1.5, p=1). Conclusion This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. These changes could be in keeping with the known mechanism of action of ozanimod and suggests that other inflammatory pathways were driving their disease activity in these patients. The significance of the changes, particularly the Castleman-like features, needs to be further investigated. Table 1: Demographic and clinical data of patients treated with ozanimod and control patients Figure 1: Representative images of lymph nodes from patients with UC treated with ozanimod and control patients showing significant sinus dilatation in patients receiving ozanimod