Increased Rates of Early Adverse Reaction to Azathioprine in Patients with Crohn's Disease Compared to Autoimmune Hepatitis: A Tertiary Referral Center Experience

Abstract

Idiosyncratic drug hypersensitivity may occur at increased rates in specific patient populations. Azathioprine has a significant early adverse reaction (EAR) profile, which includes an acute syndrome of constitutional symptoms, fever, rash, and acute pancreatitis and often requires discontinuation of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and autoimmune hepatitis (AIH). Our aims were to investigate differential rates of EAR to azathioprine in CD compared to AIH in a tertiary referral center population. Retrospective chart review of consecutive CD and AIH patients who were initiated on azathioprine in our inflammatory bowel disease (IBD) and hepatology centers was performed. EAR (fevers and constitutional symptoms, severe arthralgias, nausea, and vomiting) were defined as those occurring within 1 month of initiation. EAR rates between AIH and CD patients were compared using the Fisher's exact test. One hundred and forty-three CD (88F/55M; age 39.2 +/- 13 yr) and 40 AIH (35F/5M; age 53.1 +/- 14 yr) patients were studied. All patients were initiated with equivalent azathioprine dosage (50 mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to 51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test; p= 0.008). EAR excluding nausea and vomiting were still significantly higher in CD patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test; p= 0.01). All patients with EAR required drug discontinuation and 7% of CD patients required hospitalization for management of these complications. CD patients represent a unique subgroup at increased risk of EAR to azathioprine. Mechanisms behind these reactions need to be further defined.