Histologic manifestations of ocrelizumab-associated intestinal and hepatic injury in patients with multiple sclerosis

Abstract

Aims: Ocrelizumab is a humanized anti-CD20-monoclonal antibody that has recently been approved for the treatment of certain types of multiple sclerosis. Isolated case reports of ocrelizumab-associated colitis have been reported in the literature. We present a case series of ocrelizumab-associated intestinal injury with a focus on histopathologic features and report a case of ocrelizumab-associated hepatitis.

Methods and results: A retrospective computerized search was conducted from 03/2017 to 08/2022, which identified six patients with suspected or clinically confirmed ocrelizumab-associated intestinal injury and one patient with hepatic injury. Pertinent clinical, endoscopic, and histopathologic findings were reviewed and recorded. Seven patients (six female, one male) were identified with ages ranging from 24 to 68 years. The presenting symptoms included diarrhoea (n = 5), abdominal pain (n = 3), hematochezia (n = 2), and vomiting (n = 1), nausea (n = 1) fever (n = 1), and weight loss (n = 1). Endoscopic findings ranged from normal (n = 1) to patchy colonic inflammation with or without ulceration (n = 4) and decreased mucosal vascular pattern in the rectum (n = 1). Crohn's disease was clinically suspected in two patients and ulcerative colitis in one patient. None of the patients had a prior confirmed diagnosis of inflammatory bowel disease. Histologic patterns of initial colonic injury included acute colitis/proctitis (n = 5), and chronic active colitis (n = 1). Follow-up ranged from 1 to 3 years and 10 months. All patients were alive at follow-up. Follow-up biopsies were available for four patients and findings included focal acute colitis (n = 1), apoptotic colopathy (n = 1) lymphocytic colitis (n = 1), and normal mucosa (n = 1). Four patients were treated with steroids and ocrelizumab was discontinued in three patients. Two patients were symptomatically managed with subsequent resolution of symptoms. The liver biopsy from the patient with a marked hepatic pattern of liver enzyme elevation showed an acute hepatitis pattern of injury with prominent centrilobular necrosis, which resolved upon discontinuation of the drug and treatment with steroids and azathioprine.

Conclusions: The histologic manifestations of ocrelizumab-associated intestinal injury are variable and can mimic inflammatory bowel disease. Hepatic injury can rarely manifest as an acute hepatitis pattern of injury with necrosis. Identifying ocrelizumab-associated injury is paramount in determining management, which often includes discontinuation of ocrelizumab therapy, and/or administration of immunosuppressive therapy.

Keywords: colitis; hepatitis; histologic; multiple sclerosis; ocrelizumab.