| Autor: |
Hu, Yuqi, Gao, Le, Zhou, Lingyue, Liu, Wenlong, Wei, Cuiling, Liu, Boyan, Sun, Qi, Tian, Wenxin, Chu, Rachel Yui Ki, Song, Song, Cheng, Franco Wing Tak, Chan, Joe Kwun Nam, Ng, Amy Pui Pui, Lo, Heidi Ka Ying, Lee, Krystal Chi Kei, Chang, Wing Chung, Wong, William Chi Wai, Chan, Esther Wai Yin, Wong, Ian Chi Kei, Chai, Yi |
| Předmět: |
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| Zdroj: |
PLoS Medicine; 12/5/2024, Vol. 21 Issue 12, p1-15, 15p |
| Abstrakt: |
Background: Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear. Methods and findings: We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use. Conclusions: Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary. Yuqi Hu, Le Gao and colleagues compare the incidence of haematological malignancies between clozapine and olanzapine users using territory-wide electronic health records from Hong Kong public health facilities. Author summary: Why was this study done?: Preliminary epidemiologic evidence has been reported on an elevated risk of hematological malignancy (HM) associated with clozapine use. The clinical significance (or insignificance) of such a risk is yet to be determined. Analytic cohort studies are needed to estimate the rate difference, i.e., number of additional cases associated with clozapine use, in addition to rate ratios. What did the researchers do and find?: Using the territory-wide electronic health records from Hong Kong public healthcare facilities, we built a retrospective cohort to compare the incidence of HM between clozapine and olanzapine users. Similar with previous research, we found a 2-fold elevated rate of HM in clozapine users. Nevertheless, the rate difference between clozapine and olanzapine users were small, i.e., approximately 1 additional case of HM in every 1,700 person-year of exposure to clozapine. What do these findings mean?: The previously observed elevated risk of HM associated with clozapine is supported by territory-wide data in Hong Kong. The absolute rate difference is small and, given existing risk mitigation measures for hematological abnormalities, does not necessitate additional restrictions on the indication of clozapine or special warnings. As the assignment of clozapine versus olanzapine use in this cohort was not randomized, there may be underlying factors that are related to both clozapine use (versus olanzapine) and HM that gave rise to the observed association but were not considered. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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