OBJECTIVES: The Clozapine Risk Evaluation and Mitigation Strategy (REMS) was originally introduced by the US Food and Drug Administration to mitigate clozapine-induced neutropenia risk. Its February 2019 update required prescriber and pharmacy certifications before prescribing or dispensing clozapine. This study examines the impact of the Clozapine REMS update on neutropenia outcomes among clozapine users.

METHODS: This study used administrative claims data from the Komodo Research Dataset linked to Komodo Lab Results. Eligible patients were adults aged ≥18 years who had absolute neutrophil count (ANC) values reported and an outpatient pharmacy dispensing of clozapine in the prior 30 days, in any calendar month from January 2017 through July 2023. Distribution of the neutropenia outcomes (mild [ANC 1000-1499/μL], moderate [500-999/μL], severe [<500/μL]) was calculated monthly and analyzed via interrupted time series analysis, comparing pre-update (January 2017-December 2018; 3-month anticipatory period excluded) and post-update (March 2019-July 2023) periods.

RESULTS: Of the monthly eligible clozapine users, the pre-update period presented neutropenia for 0.09-0.68% of users, and the post-update presented neutropenia for 0.24-1.11% of users. The Clozapine REMS update resulted in an immediate increase in mild neutropenia (IRR=1.63 [1.03-2.65]), but no statistical significance was observed in moderate (IRR=1.63 [0.47-7.10]) and severe neutropenia outcomes (IRR=0.85 [0.36-2.12]). Month-to-month changes post-update were relatively small (1.01≤IRR≤1.07) for all outcomes, despite visualizable differences in trend slopes across the periods.

CONCLUSIONS: Increased mild neutropenia was observed after the 2019 Clozapine REMS update, which may reflect early detection of neutropenia as intended by the program. This finding is preliminary and limited to clozapine users with ANC result availability. Further research should explore stratification by adherence to ANC monitoring frequency per recommendation by the Clozapine REMS.