Ocrelizumab-induced acute pancreatitis: case report of an uncommon side effect of multiple sclerosis treatment

Introduction and importance: Ocrelizumab, an anti-CD20 monoclonal antibody for multiple sclerosis (MS), has a generally favorable safety profile; however, acute pancreatitis is a rare and under-recognized adverse event. Awareness of this potential association is important to ensure timely diagnosis and reporting in patients on ocrelizumab who present with abdominal symptoms. Case presentation: A 57-year-old man with MS receiving 6-monthly ocrelizumab injections presented with 3 days of epigastric pain radiating to the back, with nausea and vomiting. He denied recent alcohol use and had no history of gallstones. Laboratory tests showed lipase 854 U/L (10–140) and amylase 528 U/L (30–110) with otherwise unremarkable liver enzymes, calcium, lipids, and IgG subclasses. Abdominal ultrasound demonstrated no cholelithiasis, biliary or pancreatic duct dilatation, or peripancreatic collection. His medications included carbamazepine (commenced 5 years earlier without prior pancreatitis) and folic acid. Symptoms improved with conservative management, and he was discharged with outpatient follow-up. Clinical discussion: Drug-induced pancreatitis accounts for approximately 2% of acute pancreatitis cases. In clinical trials of ocrelizumab (OPERA I/II, ORATORIO), a handful of pancreatitis cases were reported, some with alternative risk factors; others occurred without gallstones or hypertriglyceridemia. The mechanism remains uncertain but may relate to immune dysregulation following B-cell depletion with downstream T-cell-mediated inflammation. Using the Naranjo scale, this case scores as a “possible” adverse drug reaction. Based on Badalov classification, ocrelizumab aligns with Class III, reflecting limited published data and no rechallenge evidence. Concomitant carbamazepine remains an important confounder. Conclusion: Pancreatitis should be considered in ocrelizumab-treated patients presenting with abdominal pain, even when routine risk factors are absent. Early recognition enables appropriate management and contributes to a growing evidence base needed to clarify pathophysiology and refine risk stratification for this uncommon adverse event.