: Ocrelizumab, an anti-CD20 monoclonal antibody (mAb), is a highly effective disease-modifying treatment in multiple sclerosis (MS). Despite being well-tolerated, the risk of inflammatory bowel disease has been recently recognized as a potential complication. : To report the first case of concomitant ocrelizumab-associated colitis and pancreatitis and a case of a complicated and lengthy course of colitis following the first and only dose of ocrelizumab. : Case Series : Case 1: A 25-year-old female with relapsing-remitting MS (RRMS) developed colitis and pancreatitis after the third dose of ocrelizumab. She was treated conservatively, and ocrelizumab was discontinued with no further gastro-intestinal (GI) manifestations. Case 2: A 45-year-old female with primary progressive MS (PPMS) presented with colitis and erythema induratum following the first and only dose of ocrelizumab. Treatment required the discontinuation of ocrelizumab, antibiotic regimens, corticosteroids, and eventually ustekinumab with no further colitis relapse. : We presented the first case of colitis and pancreatitis and a challenging case of colitis post-ocrelizumab administration requiring individually tailored treatment strategies. In the absence of clear predisposing factors and a consensus for treatment, clinicians should remain vigilant in case of GI symptoms in patients receiving anti-CD20 therapy.
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