Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases--A Prospective Study on Incidence and Severity

Abstract

Background and aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors.

Methods: We studied 510 IBD patients [338 Crohn's disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines.

Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses.

Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor.

Keywords: Azathioprine; Crohn’s disease; inflammatory bowel disease; lipase; pancreatitis; smoking; ulcerative colitis.

Figure 1.

Study flow. ICF, informed consent form; AZA, azathioprine.

Figure 2.

Percentages of patients with different smoking behaviours in patients with and without AIAP. Except never smokers, all differences were significant. AIAP, AZA-induced acute pancreatitis.

Figure 3.

Prevalence of elevated lipase values after azathioprine [AZA] induction ahead of acute pancreatitis. Similar amounts of patients with or without AZA-induced acute pancreatitis had at least one lipase count above the upper limit of normal after AZA induction. AIAP, AZA-induced acute pancreatitis. All differences are non-significant. ^aOne of the two AIAP patients in this group had asymptomatic 19.2-fold elevated lipase at noon on January 24, 2013; clinical signs of AIAP started on January 25, 2013 at 2 am.