CASE DESCRIPTION
A 52-year-old woman with Crohn's disease on risankizumab presented with acute epigastric pain radiating to the back and nausea for 1 day. She has been maintained on risankizumab for 2 years. Owing to ongoing Crohn's symptoms and endoscopic activity, risankizumab was optimized from every 8 weeks to every 4 weeks duration, about 3 months before current presentation.
She was a former smoker who had quit smoking 6 years before admission. She denied alcohol use, gallstones, or personal or family history of dyslipidemia or pancreatitis. Physical examination was notable for epigastric and left upper-quadrant tenderness with no xanthomas or other clinical findings suggestive of dyslipidemia.
Laboratory test results showed leukocytosis (12.7 × 109/L), microcytic anemia (hemoglobin 9.8 g/dL), lipase 155 U/L (normal 10–60), and C-reactive protein > 300 mg/L. Computed tomography imaging confirmed acute pancreatitis.
A fasting lipid panel revealed triglyceride (TG) level at 754 mg/dL, total cholesterol of 350 mg/dL, and high-density lipoprotein of 23 mg/dL. Further investigations for alternative etiologies of acute pancreatitis including liver function tests, alkaline phosphatase, bilirubin, calcium, hemoglobin A1c, and immunoglobulin G subclass 4 were within normal limits. Unfortunately, the patient's lipid baseline before risankizumab is not available.
Abdominal ultrasound showed no gallstones. Therefore, hypertriglyceridemia was considered the most likely etiology after exclusion of other common causes. Management included bowel rest, fluid resuscitation, and pain control with marked clinical improvement.
The TG level improved to 553 and 359 mg/dL before discharge.
About 2 months after the acute pancreatitis episode, and 2 days after risankizumab injection, a repeat lipid panel revealed worsening of TG level to 1,538 mg/dL, despite no dietary changes and maintained regular physical activity.
Secondary causes of hypertriglyceridemia were excluded, including hypothyroidism, diabetes chronic kidney disease, excessive alcohol use, obesity, high saturated fat or high glycemic index diet, and recent steroid exposure. Familial dyslipidemia was considered unlikely given the absence of family history.
Given the temporal association between risankizumab dose increase and triglyceride elevation, and the absence of common causes of hypertriglyceridemia, risankizumab-associated hypertriglyceridemia was highly suspected. Based on lipid clinic recommendation, risankizumab has been switched to upadacitinib and patients started on fenofibrate 160 mg daily and icosapent ethyl 2 g twice daily. The evolution was marked by the improvement of triglycerides level to 414 mg/dL, over 6-month follow-up from the acute pancreatitis without recurrence of pancreatitis.
Based on the described information, The Naranjo Adverse Drug Reaction Probability Scale score was 8, indicating a probable drug-related adverse event.
DISCUSSION
The risk of pancreatitis increases significantly when triglyceride levels exceed 1,000–2,000 mg/dL, although susceptibility varies among individuals and in some cases, lower triglyceride may be found due to inability to eat before the diagnosis.1 It is believed that hypertriglyceridemia causes excess of free fatty acid and chylomicrons, leading to increased plasma viscosity, which is responsible for pancreatic tissue ischemia and acidosis, and triggers activation of digestive enzymes and organ inflammation.2 Many disorders can lead to hypertriglyceridemia, including, but not limited to, obesity, hypothyroidism, some inflammatory diseases, and medications (estrogen and glucocorticoid).3 In a metanalysis studying lipid levels in patients with inflammatory bowel disease (IBD), there was no statistically significant difference in triglyceride levels between patient with IBDs and healthy patient.4 A postmarketing U.S. Food and Drug Administration review identified pancreatitis as an unexpected but weak safety signal, with approximately 30 cases among more than 10,000 reports.5 To our knowledge, only 1 published case reporting temporally association of hyperviscosity syndrome due to severe hypertriglyceridemia and risankizumab use. In that case, risankizumab was administered every 90 days for the past 2 years for the management of psoriasis.
The patient's TG baseline was around 200-500 mg/dL, subsequently exceeded 7,000 mg/dL about 1 month from the last risankizumab injection. Symptoms were suggestive of hyperviscosity syndrome without signs of acute pancreatitis. Despite the presence of risk factors, the acute presentation raised the suspicion of adverse drug reaction due to recent use of risankizumab.6 Similarly, in our case, the rapid increase of TG level, despite no changes other than escalated dose of risankizumab, further highlights the possible association between the risankizumab and the occurrence of severe hypertriglyceridemia complicated with acute pancreatitis.
We believe that further studies, specifically those including monitoring of TG level in patients receiving risankizumab, are needed to further evaluate this potential association and help prevent serious events such as pancreatitis.
DISCLOSURES
Author contributions: All authors contributed substantially to the conception, drafting, and critical revision of the manuscript. All authors approved the final version and agreed to be accountable for all aspects of the work. D.
Hudhud is the article guarantor.
Financial disclosure: None to report.
Informed consent was obtained for this case report.