Dupilumab-Induced Pancreatitis

ABSTRACT

Drug-induced pancreatitis (DIP) is a rare cause of pancreatitis with an extensive and growing list of offending medications. Drawing a causative relationship between a medication and pancreatitis can be challenging, requiring a thorough workup to exclude other potential etiologies. By using scoring systems to identify DIP, we have identified another case of suspected DIP. In this study, we present a case of pancreatitis 10 days after initiation of dupilumab. An evaluation for other causes was unrevealing. As dupilumab use increases, providers should be aware of this possible adverse effect.

INTRODUCTION

Acute pancreatitis is one of the major gastrointestinal causes of emergency department visits, hospitalization, and overall cost in health care.¹ Drug-induced pancreatitis (DIP) is one of the rarer etiologies of pancreatitis, and numerous drugs have been implicated. Dupilumab is a humanized monoclonal antibody approved by the Food and Drug Administration in 2017. It is used for the treatment of moderate-severe atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.² It reduces inflammation by inhibiting interleukin-4 and interleukin-13 signaling.³ We present a case of pancreatitis secondary to dupilumab.

CASE REPORT

A 60-year-old man with a medical history of allergic rhinitis and nasal polyposis presented with nausea and back pain that migrated to the abdomen. He was recently started on dupilumab for nasal polyps, and his first dose was 10 days before presentation. The patient had no history of pancreatitis or alcohol use. He had no family history of pancreatitis. He had undergone a cholecystectomy 2 years before admission for cholelithiasis. Vitals were unremarkable and physical examination showed epigastric tenderness to palpation. Laboratory studies were notable for significant elevation in lipase at 1,087 U/L (upper limit of normal: 65 U/L), aspartate aminotransferase 85 U/L (upper limit of normal: 45 U/L), alanine aminotransferase 63 U/L (upper limit of normal: 40 U/L), and normal serum triglyceride and calcium levels. The patient was treated with bowel rest, intravenous fluids, antiemetics, and pain medication. Magnetic resonance cholangiopancreatography showed hepatic and renal cortical cysts with no evidence of anatomic pancreatic abnormalities or choledocholithiasis. He was hospitalized for 3 days, and diet was slowly advanced along with symptom resolution. Given the absence of other causes of pancreatitis and the temporal relationship between the episode of pancreatitis and the initiation of the drug, he was believed to likely have DIP and was not rechallenged with dupilumab. He underwent an endoscopic ultrasound after discharge, which confirmed the absence of choledocholithiasis and found no other explanation for pancreatitis.

DISCUSSION

Of the many causes of acute pancreatitis, DIP can be the most challenging to prove. Ruling out other potential causes of acute pancreatitis is necessary before establishing a diagnosis of DIP.

In this instance, the patient had recently initiated dupilumab and had no other risk factors of pancreatitis. Magnetic resonance cholangiopancreatography and endoscopic ultrasound excluded choledocholithiasis. There were no findings of chronic pancreatitis, mass, or pancreas divisum. Therefore, our suspicion for DIP was high. Redevelopment of pancreatitis in this patient, especially without repeat exposure to dupilumab, should prompt further investigation into autoimmune or neoplastic etiologies and may warrant tissue sampling.

Rechallenging the patient with the suspected drug can further establish the diagnosis of DIP.⁴ DIP only accounts for 1%–2% of all pancreatitis cases, but there are over 500 identified causative medications, and the list is only expected to increase.^5,6 DIP is typically associated with mild or moderately severe pancreatitis with overall favorable outcomes.⁷ Establishing a causative relationship between medications and pancreatitis has been historically difficult. Two scoring systems have been developed as an objective measure of determining DIP: the Naranjo Adverse Drug Reaction Probability Scale and the Badalov classification system.⁷ Our case yielded a Naranjo score of 5, consistent with a probable correlation.^8,9 Per the Badalov classification, dupilumab would be considered a Class III medication (minimum of 2 case reports, no rechallenge of the latency period).¹⁰

Pancreatitis is not a listed adverse effect of dupilumab. Known adverse reactions include injection site reactions, eosinophilia, and conjunctivitis.² In addition, dupilumab-induced pancreatitis has only been rarely described in the literature. The first case report was associated with the development of pancreatitis in 2 adolescent boys.¹¹ However, there was no recurrence on rechallenge, and they were both historically on medication that has been previously associated with pancreatitis. The second case report was described in a 40-year-old man after administration of his second dose of dupilumab.¹² No rechallenge was attempted. The Naranjo scores for these 3 cases ranged from 2 to 5. As dupilumab use becomes more common with expanded indications, such as eosinophilic esophagitis, providers should be aware of the possible link between this medication and pancreatitis.

DISCLOSURES

Author contributions: All authors were involved in the collection of data and drafting of the manuscript. All authors gave final approval of the version to be published and agreed to be accountable for aspects of the work. S.M. Govani is the article guarantor.

Financial disclosure: None to report. S.M. Govani is a speaker for AbbVie and Bristol Meyer Squibb.

Informed consent was obtained for this case report.