Authors: Sandeep Dhanda 1, 2, Vicki Osborne 1, 2, Debabrata Roy 1, 2, Saad Shakir 1, 2
Affiliations: 1 Drug Safety Research Unit, 2 University of Portsmouth
Clinical trials have reported specific safety concerns such as acute pancreatitis (AP) in patients (pts) taking Bydureon® (exenatide once-weekly) for type 2 diabetes mellitus (T2DM). A Post-Authorisation Safety Study (PASS) was conducted to monitor the real-world safety of Bydureon® in primary (1o) care in England.
To estimate the incidence of targeted safety outcomes in pts prescribed Bydureon® in 1o care.
Pts identified from dispensed Bydureon® prescriptions in England (2012-2016). Questionnaires sent to prescribing general practitioners (GPs) at ≥12-months observation collected event information. Events of interest included AP, pancreatic cancer (PC), thyroid neoplasm (TN), gallstones, biliary colic or cholecystitis (GBC), acute renal failure (ARF), type 1 hypersensitivity (T1H), and cardiac events (CE). 12-month incidence estimates (on Bydureon® or ≤10 weeks after stopping) were calculated; results were stratified according to prior exenatide use (i.e. Byetta®).
Questionnaire response rate= 37.2% (7752/20860). Total cohort = 6294 pts prescribed Bydureon® for T2DM (median age 57 years [IQR 50, 65]; 55.2% male). Exenatide naïve n=4556 (72.4%), previous Byetta® users n=1629 (25.9%), previous Byetta® use unknown n=109 (1.7%).
Risk of AP in total cohort 0.2% (95% CI [0.1, 0.4]; n=14). 2 pts had a prior history. Risk of AP was similar for exenatide naïve (0.2% (95% CI [0.1, 0.4]; n=10) and previous Byetta® users (0.2% (95% CI [0.0, 0.5]; n=3). Rate of AP in total cohort was 2.5/1000 person-years (95% CI [1.5, 4.3]) and no statistically significant difference was observed between the 2 user groups. Time-to-event analyses suggested no clear pattern in the hazard function of AP over time. For 12 of the 14 pts, Bydureon® was stopped due to AP. AP complications; necrosis/pseudocyst n=1, fatal outcome n=1.
PC 0.1% (n=4); a fatal outcome was reported in 3 of these pts. TN 0.0% (n=0). GBC 0.6% (95% CI [0.4, 0.8]; n=38); 15 of which had a prior history of GBC. ARF 0.5% (95% CI [0.3, 0.7]; n=29). T1H 0.7% (95% CI [0.5, 0.9]; n=44). CE 3.6% (95% CI [3.2, 4.1]; n=227). No statistically significant differences in risk between the 2 user groups were observed.
Incidence of AP was low in Bydureon® users and consistent with prior clinical trial/observational data. No unexpected findings were identified. This study has unique strengths, including collection of timely, granular real-world data from GPs, facilitating accurate estimates. The study is part of a broader literature on the safety of Bydureon® and conclusions should be made in context with other post-marketing findings.
The DSRU is an independent charity (No 327206), which works in association with the University of Portsmouth. The DSRU has received funding from AstraZeneca AB, the manufacturer of Bydureon®. The DSRU makes the final decision on the publication of external communications.