MSc Student Leslie Dan Faculty of Pharmacy, University of Toronto, Canada
Background: In 2005, the FDA released a black-box warning for Topical Calcineurin Inhibitors (TCIs) and Health Canada released subsequent public advisories concerning a hypothetical risk of malignancy associated with these medications. In the years following the initial safety communications, multiple studies have found been conducted, producing no clear evidence that TCIs are associated with the risk of malignancy. In 2018, the Canadian Dermatology Association released a positioning statement communicating the lack of evidence associated with the initial TCI warnings.
Objectives: To examine the impact of the safety announcements on the monthly rate of TCI users.
Methods: We conducted a cross-sectional analysis with administrative claims data from Ontario to measure the monthly change in the rate of TCI users before and after each announcement (April 2005 and May 2018). We included all patients eligible for the Ontario Drug Benefits program and stratified the data according to patient age, sex, geographic location, history of cancer, type of user (new and prevalent users), and prescriber specialty. We used an autoregressive integrative moving average (ARIMA) model to assess the post-announcement change in drug utilization. The primary outcome was the overall change in monthly TCI rates following each announcement and the secondary outcome was the change in rates among new and prevalent users stratified by patient subgroups and prescriber specialty.
Results: Following the 2005 safety communications, we observed a significant ramp decrease in the rate of TCI (-13.15 per 100,000, p=0.0004). Within the stratified analysis, we found a significant reduction in the rate of TCI users aged 65+ (-8.28 per 100,000, p=0.0003)and new users (-8.68 per 100,000, p=0.0012). Following the 2018 safety communication from the CDA, we observed a significant reduction in the rate of new TCI users (-8.44 per 100,000, p=0.0026), all users aged 25 to 64 (-21.57 per 100,000, p=0.0028) and all users with no history of cancer (-10.43 per 100,000, p=0.0017). The rate of prevalent users remained unchanged following both safety announcements.
Conclusions: Safety announcements concerning the hypothetical malignancy concerns were associated with substantially lower rates of TCI prescriptions in Ontario. Conversely, the reassuring communication in 2018 was associated with a small increase in TCI use. These findings suggest the impact of safety communications on a patient's therapeutic decisions varies by certain patient characteristics, and considerations for vulnerable subgroups of patients should be accounted for in future risk communications.
