Ozanimod-exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histological Changes.

Abstract

Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histological changes which occur in the lymph nodes of patients on ozanimod is unknown. This retrospective study included patients with ulcerative colitis [UC] undergoing total colectomy for treatment-refractory disease who received ozanimod, 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 was reviewed and multiple features were scored by experienced pathologists. Six [13%] ozanimod-treated patients with UC required surgery for treatment-refractory disease. Colectomy specimen data were available for five patients [one patient had surgery at an outside centre]. Lymph node specimens from six control patients with UC who had colectomy were examined. Histological examination of lymph nodes showed that patients treated with ozanimod had significantly greater extent of dilated sinuses [p = 0.03] and greater degrees of sinus histiocytosis [p = 0.03] compared with control patients. In addition, there was a trend towards more Castleman-like angiotrophic hyperplasia, plasma cell infiltration, and subcortical interfollicular expansion in ozanimod-treated patients. This study identifies unique histological changes in the lymph nodes of patients with UC treated with ozanimod. The presence of sinus histiocytosis and dilated sinuses is in keeping with the known mechanism of action of ozanimod, and suggests that blocking lymphocyte egression from lymph nodes was insufficient to ameliorate disease severity in these patients. The possibility of Castleman-like features, identified in several of the cases, needs to be further investigated.