Cost effectiveness of pharmacogenetic-guided clozapine administration based on risk of HLA variants in Japan and the UK

Abstract

Pharmacogenetics/pharmacogenomics have enabled the detection of risk of human leukocyte antigen (HLA) variants for clozapine-induced agranulocytosis/granulocytopenia (CIAG). To apply this evidence to the clinical setting, we compared the cost-effectiveness of the proposed “HLA-guided treatment schedule” and the “current schedule” being used in Japan and the United Kingdom (UK) (absolute neutrophil count (ANC) cutoff at 1500/mm3); in the “HLA-guided treatment schedules,” we considered a situation wherein the HLA test performed before clozapine initiation could provide “a priori information” by detecting patients harboring risk of HLA variants (HLA-B*59:01 and “HLA-B 158T/HLA-DQB1 126Q” for Japanese and Caucasian populations, respectively), a part of whom can then avoid CIAG onset (assumed 30% “prevention rate”). For the primary analysis, we estimated the incremental cost-effectiveness ratio (ICER) of “HLA-guided treatment schedule” and “current schedule” used in Japan and the UK, using a Markov model to calculate the cost and quality-adjusted life years (QALYs) over a 10-year time period. Furthermore, as an explorative analysis, we simulated several situations with various ANC cutoffs (1000/mm3 and 500/mm3) and plotted the cost/QALYs for each option to identify the best, or estimate the next best candidate option applicable in actual clinical settings. The primary probabilistic analysis showed that the “HLA-guided treatment schedule” was more cost effective than the “current schedule”; the ICER was £20,995 and £21,373 for the Japanese and the UK populations, respectively. Additional simulation revealed that the treatment option of ANC cutoff at 500/mm3 without HLA screening was the most cost-effective option; however, several options may be candidates to break away from the “current schedule” of ANC cutoff at 1500/mm3. Owing to its cost-effectiveness, we propose such pharmacogenetic-guided/pharmacogenomic-guided clozapine treatment for use in the real-world setting, which provides key information for optimization of clinical guidelines for high-risk patients for gradual change of clozapine treatment schedule under the safety consideration.

Clozapine-Related Functional Bowel Obstruction: A Rare Adverse Effect Unmasking Quetiapine and Benztropine Interaction Raising Need for Bowel Surveillance

“…4 Clozapine has shown a significant decrease in hospitalization and cost of treatment with a concomitant increase in qualityadjusted life years. 1,[5][6][7] Its increased use has also shed light on its lesser known side effect of CIGH.…”

Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis

“…The US changes simplify clozapine monitoring and enable more patients to initiate and continue treatment without endangering their health 34 . A lower threshold of 0.5 × 10 9 /L also is the most cost-effective method of blood monitoring with clozapine 35 , in the absence of genetic testing. Alignment of the UK guidelines with the revised US Food and Drug Administration monitoring guidelines would have a similar positive impact on improving the use of clozapine without compromising safety 12 , 36 .…”