Frequency of neutropenia over time in patients on clozapine

Abstract

ABSTRACTBackgroundClozapine, the only evidence-based drug for treatment-resistant schizophrenia is associated with agranulocytosis. For this reason, all clozapine patients are required to undergo mandatory regular blood monitoring throughout their clozapine treatment. The blood test results are reported using a traffic light system. The clozapine treatment is stopped immediately after a confirmed red result, which is the indication for risk of agranulocytosis. The need for blood tests places a burden on patients and acts as a barrier to clozapine treatment. There is growing evidence that the risk of agranulocytosis falls steeply after the first few months of treatment, raising the possibility that clozapine monitoring could be discontinued after a certain period of treatment.AimTo investigate the frequency density of the confirmed red results from clozapine monitoring across clozapine treatment.MethodBy merging electronic health records (EHR) data with clozapine blood monitoring data, we identified the clozapine treatment dates. The EHR data was from South London and Maudsley NHS Foundation Trust (SLAM). The clozapine blood monitoring data was from Zaponex Treatment Access System (ZTAS). ZTAS is one of the mandatory blood monitoring service providers in the United Kingdom. From these data, Kaplan-Meier survival curve was fitted to determine the time to get confirmed red results. At fixed points in the treatment, the future risk of obtaining a red result were calculated.ResultsBy merging over 301,000 data points that came from the blood monitoring results and EHR data of 1,362 patients, we identified 1,891 clozapine treatment periods. Of these, 75 treatments were stopped due to confirmed red results. The Kaplan-Meier survival curve and the incidence rates data showed that 56 (74.7%) confirmed red results occur within the first 6 months of clozapine treatment.ConclusionWe found a contrast between the relatively high density of the confirmed red results at the beginning of clozapine treatment which significantly reduces after 6 months of treatment which remained low thereafter.